Clinical Practice Guidelines For The Obstetrician - Gynecologist

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Society of Gynecologic Oncologists

of the Philippines (Foundation), Inc.
!
CLINICAL PRACTICE GUIDELINES
for the
OBSTETRICIAN - GYNECOLOGIST
!
Second Edition
November 2010!
TABLE OF CONTENTS
PAGE
Foreword i
Preamble ii
SGOP Officers 2008-2010 iii
SGOP 2010 General Membership iv
Geographical Distribution of Gynecologic Oncologists v
Ad Hoc Committee for the Clinical Practice Guidelines 2010 vi
CLINICAL PRACTICE GUIDELINES
Cervical Cancer 1
Ovarian Cancer
Endometrial Cancer
Vulvar Cancer
Vaginal Cancer
Breast Cancer
APPENDIX
FOREWORD
Medicine is a dynamic field, it is continuously evolving. This is especially

true in the field of Gynecologic Oncology. A lot of developments or changes
have occurred in just a couple of years. Changes that we should learn and
incorporate in our practice in obstetrics and gynecology in order to give the best
quality health care to the patients we serve.
The first edition of the Society of Gynecologic Oncologists of the
Philippines (Foundation), Inc (SGOP) Clinical Practice Guidelines (CPG) for the
Obstetrician-Gynecologist in 2003 was received with great enthusiasm and
support. Thus, the Society decided to embark to publish an updated version
incorporating the many changes or new developments in the years since the
publication of the first edition.
The organization of this CPG is simple and logical; the text is well-written
and easy to understand. It is hoped that this will be of help not only to practicing
obstetrician gynecologist but also our residents in training.
I congratulate the members of the planning committee for an excellent
job. I would also give my thanks to the members of SGOP who participated in
the discussion and critique of this CPG.
Rey H. delos Reyes, MD, MHSA

President
Society of Gynecologic Oncologists of the Philippines (Foundation), Inc
2008-2010
PREAMBLE
This publication of the Society of Gynecologic Oncologists of the

Philippines, Inc. (SGOP) on the Clinical Practice Guidelines for the Obstetrician-
Gynecologists is intended to fulfill the following objectives: 1.) To equip the
obstetrician-gynecologist with the sufficient knowledge about the screening,
diagnosis and management of cancer of the female genital tract. 2.) To provide
the obstetrician-gynecologist a quick reference guide which may be used in
his/her daily clinical practice.
It is recommended that the specific diagnostic or therapeutic procedures
mentioned in this guide be performed only by specialists with certified training. It
is recommended also that obstetrician-gynecologists optimize referral to
specialists and subspecialists where his or her knowledge be incomplete or
deficient in the diagnostic and therapeutic procedures encountered.
It is hoped that this guide become a companion of the obstetrician-
gynecologist in the prevention and actual treatment of cancer of the female
genital tract. May this be a source of information that may be used to capture
disease early, to have a disease be treated correctly and promptly by the best
hands with the best training.
Efren J. Domingo, MD, PhD

Immediate Past President, SGOP
Chair, Committee for the SGOP Clinical Practice Guidelines
THE SOCIETY OF GYNECOLOGIC ONCOLOGISTS OF THE PHILIPPINES
(FOUNDATION), INC.
OFFICERS
2008-2010
REY H. DELOS REYES, MD, MHSA

President
GIL S. GONZALEZ, MD
Vice President
MA. CYNTHIA F. TAN, MD

Secretary
MA. LILIBETH L. SIA SU, MD

Treasurer
MARY CHRISTINE F. PALMA, MD

Public Relations Officer
EFREN J. DOMINGO, MD, PhD

Immediate Past President
Board of Directors
TERESITA B. CARDENAS, MD
JERICHO THADDEUS P. LUNA, MD
BENJAMIN D. CUENCA, MD
MANUEL S. MANABAT, MD
ARIS LUKE I. DUNGO, MD
CONCEPCION D. RAYEL, MD
CECILIA L. LLAVE, MD, PhD
RAFAEL S. TOMACRUZ, MD
PHILIPPINE BOARD OF GYNECOLOGIC ONCOLOGY
GIL S. GONZALEZ, MD
Chair
CECILIA L. LLAVE, MD
VIRGILIO R. OBLEPIAS, MD
Members
!
2010 GENERAL MEMBERSHIP
FELLOWS
ABAD, Rainerio S.! DUEÑAS, Rommel Z. RAÑOLA, Rona F.
AGBANLOG, Teresita P. DUNGO, Aris Luke I. RAYEL, Concepción D.
ALBANO, Amuerfina D. EVANGELISTA, Emilio Glenn B. RIVERA, Wilhelmina D.
AQUILIZAN, Leo Francis N. FAMADOR, Jay Arnold F. SABADO, Grace D.
ARIAS, Coleta B. FLAVIER, Carol Marjorie P. SALES-DIAZ, Aina R.
BANTA, Edna C. GADDI, Agnes M. SAN JUAN, Filomena S.
BAUTISTA, Aida J. GALBO, Pherdes E. SANTOS, Elmer R.
BENAVIDES, Doris R. GANZON, Esther Rhadamanthine V. Jr. SANTOS, Helen Grace T.
BENITEZ, Glenn B. GARANA, Belen T. SIA SU, Ma. Lilibeth L.
BENITEZ, Isidro B. GERMAR, Ma. Julieta Corazon V. SOLIS, Constancia Wilhelmina T.
BORJA, Manuel N. GONZALES, Ma. Gay M. SORIANO, Yvonne T.
BRESNAN, Alma M. GONZALEZ, Gil S. SOTTO, Luciano S.J. Sotto
BUIZON, Andrew Rouldan B. HUEVOS, Ma. Arlene B. SOTTO, Rene V.
CABANELA, Judith G. LLAVE, Cecilia L. STREBEL, Elizabeth E.
CACHO, Richard Ronald B. LIMSON, Genara M. SULAY, Raymond S.
CAMPOS, Ronald Agustine O. LIWAG, Arnold P. SY-FERNANDO, Victoria N.
CARDENAS, Teresita B. LUNA, Jericho Thaddeus P. TAN, Ma. Cynthia F.
CAYABYAB, Melinda M. LUNA-SUN, Ma. Patricia P. TAN-CARDOSO, German C.
COCOS, Percida S. MADURAMENTE, Myra Joy G. TOMACRUZ, Rafael S.
COLE, Lilli May T. MANABAT, Manuel S. TORAL, Jean Ann B.
CORONEL, Patricia Ann S. MANALO, Augusto M. TUPAS, Ma. Lora C.
CRISTOBAL, Ruth Judith V. MARIANO, Jocelyn Z. VALDEZ, Corazon R.
CUENCA, Benjamin D. MERCADER, Evangeline M. VILLADELGADO, Menandro A.
DANCEL, Elsie, R. MERCADO, Fe Marissa G. VILLANUEVA, Salvador Luis R.
DE CASTRO, Marie Aleli R. MORAN, Jose B. YAMBAO, Helen D.
DELA CRUZ, Melchor C. Jr. MOTIL, Gina P. ZAMORA, John-David V.
DELOS REYES, Rey H. OBLEPIAS, Virgilio R.
DIY, Norma L. PALMA, Mary Christine F.
DOMINGO, Efren J. PUA, Scheryll B.
DIPLOMATES
ATO-ANTINERO, Belina MAG-IBA, Irene B. BADILLA, Edelyn A.
GARCIA, Christine Joy G. MERCADO, Mary Evangeline V. SICAM, Renee Vina G.
GARCIA, Victorino C. Jr. ZALAMEDA-CASTRO, Carolyn R.
AFFILIATE FELLOWS
ABELARDO, Agustina D. DULAY, Robert P. PADILLA-CRUZ, Angeles
AVILA, Jose Ma. C. JACINTO, Elizabeth K. PALO-GARCIA, Fe L.
CABALUNA, Ma. Lourdes Josefina K. JOCSON, Milagros T. QUEVEDO, Ma. Carmen H.
CALAGUAS, Miriam Joy C. KRINGS, Cathy L. SY-ORTIN, Teresa T.
CANLAS, Benjamin D.† LOPEZ, Rolando A. TAN, Eduardo G.
CAPITO, Lourdes B. MANALASTAS, Ricardo M. Jr. TRINIDAD, Anne Marie L.
CHAN, Valorie F. NARCISO, Francisco V. VEGA, Gaudencio P.
CRUZ, Bernadette O. NGELANGEL, Corazon A. ZAMUCO, Jaime T.
DALMACIO-CRUZ, Adelaida D. NUQUI, Elizabeth Arcellana
HONORARY FELLOWS
CHANNEN, William PECORELLI, Sergio THOMAS, Gillian M.
MANAHAN, Constantino P. † FRIEDLANDER, Michael
!
GEOGRAPHICAL DISTRIBUTION OF GYNECOLOGIC ONCOLOGISTS IN THE
PHILIPPINES
NATIONAL CAPITAL REGION REGION I

Rainerio S. Abad, M.D.! Teresita P. Agbanlog, M.D. – Baguio City!
Amuerfina D. Albano, M.D.! Richard Ronald B. Cacho, M.D. – Pangasinan/La Union!
Leo Francis N. Aquilizan, M.D.! Ruth Judith V. Cristobal, M.D. – Ilocos Sur
Edna C. Banta, M.D.! Victorino C. Garcia Jr., M.D. – Pangasinan
Aida J. Bautista, M.D.! Yvonne T. Soriano, M.D. – Baguio City/La Union
Doris R. Benavides, M.D.! REGION II
Glenn B. Benitez, M.D.! Melchor C. dela Cruz, Jr., M.D. – Isabela/Nueva Vizcaya!
Isidro B. Benitez, M.D.! REGION III
Manuel N. Borja, M.D.! Ronald Agustine O. Campos, M.D. – Pampanga !
Judith G. Cabanela, M.D.! Agnes M. Gaddi, M.D. – Pampanga!
Teresita B. Cardenas, M.D.! Esther R. V. Ganzon, Jr., M.D. – Cabanatuan City, Nueva Ecija!
Melinda M. Cayabyab, M.D.! Corazon R. Valdez, M.D. – Olongapo City, Zambales !
Percida S. Cocos, M.D.! Jocelyn Z. Mariano, M.D. – Meycauayan, Bulacan!
Lilli May T. Cole, M.D.! Grace D. Sabado, M.D. – Tarlac, Tarlac
Benjamin D. Cuenca, M.D.! Elmer R. Santos, M.D. – Balanga, Bataan
Elsie, R. Dancel, M.D.! REGION IV
Marie Aleli R. De Castro, M.D.! Coleta B. Arias, M.D. – Lucena City, Quezon
Rey H. delos Reyes, M.D., M.H.S.A.! Belina Ato-Antinero, M.D. – Batangas City
Efren J. Domingo, M.D., Ph.D.! Belen T. Garana, M.D. – Lucena City Quezon
Rommel Z. Dueñas, M.D.! Arlene B. Huevos, M.D. – San Pablo City, Laguna!
Aris Luke I. Dungo, M.D.! Gina P. Motil, M.D. – Lucena City, Quezon!
Emilio Glenn B. Evangelista, M.D. ! Mary Evangeline A. Villa-Mercado, M.D. – Lipa. Batangas!
Jay Arnold F. Famador, M.D.! Menandro A. Villadelgado, M.D. – Tanauan, Batangas !
Victoria S. Fernando, M.D.! Andrew Rouldan B. Buizon, M.D. – Dasmarinas, Cavite!
Christine Joy G. Garcia, M.D.! Aina R. Sales-Diaz, M.D. - Biñan, Laguna
Maria Julieta V. Germar, M.D.! Salvador Luis R. Villanueva, M.D. – Los Baños, Laguna
Gil S. Gonzalez, M.D.! REGION V
Cecilia L. Llave, M.D., Ph.D.! Alma M. Bresnan, M.D. – Naga City, Camarines Sur!
Genara M. Limson, M.D.! Rona F. Rañola, M.D. – Legaspi, Albay!
Jericho Thaddeus P. Luna, M.D.! REGION VI
Irene B. Mag-iba, M.D.! Norma L. Diy – Bacolod City!
Manuel S. Manabat, M.D.! Ma. Lora C. Tupas, M.D. – Iloilo City!
Augusto M. Manalo, M.D.! Arnold P. Liwag, M.D. – Iloilo City/Bacolod City!
Jose B. Moran, M.D.! REGION VII
Virgilio R. Oblepias, M.D.! Patricia Ann S. Coronel, M.D. – Cebu!
Scheryll B. Pua, M.D.! Pherdes E. Galbo, M.D. – Cebu !
Mary Christine F. Palma, M.D.! Evangeline M. Mercader, M.D. – Cebu!
Wilhelmina D. Rivera, M.D.! Raymond S. Sulay, M.D. – Cebu!
Filomena S. San Juan, M.D.! REGION IX
Ma. Lilibeth L. Sia Su, M.D.! Ma. Gay M. Gonzales, M.D. – Zamboanga City!
Renee Vina G. Sicam, M.D.! REGION X
Rene V. Sotto, M.D.! Fe Marissa G. Mercado, M.D. – Cagayan de Oro!
Luciano S.J. Sotto, M.D.! REGION XI!
Elizabeth E. Espino-Strebel, M.D.! Edelyn A. Badilla, M.D. – Tagum City!
Ma. Patricia L. Sun, M.D.! Carol Marjorie P. Flavier, M.D. – Davao City!
Ma. Cynthia F. Tan, M.D.! Concepcion D. Rayel – Davao City!
German C. Tan-Cardoso, M.D.! Helen Grace T. Santos, M.D. – Davao City!
Rafael S. Tomacruz, M.D.! Constancia Wilhelmina T. Solis, M.D. – Davao City!
Jean Anne B. Toral, M.D.! REGION XII!
Carolyn R. Zalameda-Castro, M.D.! Helen D. Yambao, M.D. – North Cotabato!
John-David V. Zamora, M.D. ! Myra Joy G. Maduramente-Mann, M.D. – General Santos !
!
ADHOC COMMITTEE FOR THE 2010 SGOP CLINICAL PRACTICE
GUIDELINES FOR OBSTETRICIAN GYNECOLOGIST
Efren J. Domingo, MD
Editor in Chief
CERVIX
Ma. Lilibeth L. Sia Su, MD
Maria Julieta V. Germar, MD
Helen R. Amorin, MD
Angelito DL. Magno, MD
OVARY
Filomena S. San Juan, MD, PhD
Jean Anne B. Toral, MD
Anna Katrina I. Sobritchea, MD
Grace Q. Quirapas, MD
ENDOMETRIUM
Efren J. Domingo, MD, PhD
Carolyn R. Zalameda-Castro, MD
Mary Lilia Bernadette V. Tinio, MD
Rommel A. Garcia, MD
VULVA
Glenn B. Benitez, MD
Doris R. Benavides, MD
Jaynet C. de Castro-Tan, MD
Ronald B. Capito, MD
BREAST
Cecilia L. Llave, MD
Jericho Thaddeus P. Luna, MD
Ana Victoria V. Dy Echo, MD
Carlos Ray B. Sanchez III, MD
Rose Joy C. David-Vallega, MD
CERVICAL CANCER
I. INCIDENCE
! Cancer of the cervix is the second most common cancer among women
worldwide, with an estimated 493,000 new cases and 274,000 deaths in 2002.
About 83% of the cases occur in developing countries, representing 15% of
female cancers.1
! According to the Philippine Cancer Facts and Estimates, the incidence of cervical
cancer remained stable from 1980 to 2005, with an annual age-standardized
incidence rate of 22.5 cases per 100,000 women. In 2005, there were 7,277 new
cases of cervical cancer, with 3,807 reported deaths. The overall 5-year survival
rate was 44% and mortality rate was 1 per 10,000 women.2
! About 2/3 of cervical cancer in the Philippines are diagnosed in an advanced
stage, and mortality rate is high. The high mortality rates in the Philippines is due
to advanced clinical stage at presentation and to the fact that a significant
proportion of patients do not receive or complete prescribed courses of
treatment, due to deficiencies in treatment availability, accessibility and
affordability.2
References:
1. Jacques F, et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence

Worldwide, IARC Cancer Base No. 5, version 2.0 (Lyon, France: IARC, 2004), accessed
online at www.depdb.iarc.fr/globocan/GLOBOframe.htm. Accessed on January 15, 2010.
2. Laudico AV, Esteban DB, Redaniel MT, Mapua CA, and Reyes LM. 2005 Philippine
Cancer Facts and Estimates, Philippine Cancer Society, Inc., 2004.
II. RISK FACTORS
Statement 1: Human papilloma virus (HPV) infection is the necessary cause of

cervical cancer. (Level II-2, Grade A)
Supporting Statements:
A meta-analysis by the International Agency for Research on Cancer (IARC) included a

total of 10,058 cervical cancer cases from 85 published studies. The most common HPV
types identified in cervical cancer were, in order of decreasing prevalence, HPV 16, 18,
45, 31, 33, 58, 52, 35, 59, 56, 6, 51, 68, 39, 82, 73, 66 and 70. Over 2/3 of cervical
cancer cases were associated with an infection of either HPV 16 (51.0%) or HPV 18
(16.2%).1
The relationship between HPV infection and cervical cancer has been recognized in a
large body of studies, and determined as causal by international reviews since the early
1990s. The presence of HPV DNA in cervical neoplasia is the first necessary cause of a
human cancer ever identified.2-4
References:
1. Franceschi S. The IARC commitment to cancer prevention: The example of

papillomavirus and cervical cancer. Recent Results Cancer Res 2005;166:277–297.
2. Bosch FX, Lorincz A, Muñoz N, Meijer CJLM, Shah KV. The causal relation between
human papillomavirus and cervical cancer. J Clin Pathol 2002;55:244-65.
3. Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH,
Moreno V, Kurman R, Shah KV. Prevalence of human papillomavirus in cervical cancer:
a worldwide perspective. International biological study on cervical cancer (IBSCC) study
group. J Natl Cancer Inst 1995;87:796-802.
4. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ,
Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive
cervical cancer worldwide. J Pathol 1999;189:12-9.
Statement 2: Parity of 7 or more increases the risk for cervical cancer. (Level II-2,
Grade A)
Women who reported ! 7 full term pregnancies and were HPV-positive had a 4-fold
increase in risk of cervical cancer compared with nulliparous HPV-positive women with
similar characteristics (Odds Ratio [OR] 3.8; 95% CI 2.7-5.5). There was still a 2.6-fold
increase in risk when women reporting 7 or more pregnancies were compared with HPV-
positive women reporting 1 or 2 full term pregnancies.1
High parity may increase the risk of cervical cancer because it maintains the
transformation zone on the ectocervix for many years facilitating the direct exposure to
HPV and, possibly, to other co-factors. Hormonal changes induced by pregnancy
(increased levels of estrogen and progesterone) may also modulate the immune
response to HPV and influence risk of persistence or progression.2
References:
1. Muñoz N, Franceschi S, Bosetti C, et al. Role of parity and human papillomavirus in

cervical cancer: the IARC multicentric case-control study. Lancet 2002 Mar
30;359(9312):1093-101.
2. International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical
carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563
women with cervical carcinoma and 33,542 women without cervical carcinoma from 25
epidemiological studies. Int J Cancer 2006;119:1108-1124.
Statement 3: Long-term use of oral contraceptive pills (OCPs) could increase the
risk of cervical cancer by up to fourfold in women with HPV infection. (Level II-2,
Grade A)
An analysis of pooled data from 10 case-control studies of patients with invasive cervical
cancer or carcinoma in situ (CIS) showed that among current users of OCP, the risk of
invasive cervical cancer increased with increasing duration of use (Relative Risk [RR] for
! 5 years use vs. never use, 1.90; 95% CI 1.69-2.13). The risk declined after use
ceased, and by ! 10 years had returned to that of never users. A similar pattern of risk
was seen both for invasive and in-situ cancer, and in women who tested positive for high
risk HPV.1
Using an OCP for < 5 years was not related to cervical cancer (OR 0.77; 95% CI 0.46-
1.29) but the risk increased significantly with a use of 5 to 9 years (OR 2.72; 95% CI
1.36-5.46) and with a use of ! 10 years (OR 4.48; 95% CI 2.24-9.36). Hormone-related
mechanisms may influence the progression from premalignant to malignant cervical
lesions by promoting integration of HPV DNA into the host genome, which results in
deregulation of E6 and E7 expression. An experimental study has shown that estradiol
may stimulate the transcription of HPV 16 E6 and E7 in cell lines that contain integrated
HPV 16.2
The RR of cervical cancer is increased in current users of OC and declines after use
ceases. A 10-year use of OCP from around age 20 to 30 years is estimated to increase
the cumulative incidence of invasive cervical cancer by age 50 from 7.3 to 8.3 per 1000
in less developed countries and from 3.8 to 4.5 per 1000 in more developed countries.3
References:
1. Moreno V, Bosch FX, Muñoz N, et al. Effect of oral contraceptives on risk of cervical
cancer in women with human papillomavirus infection: the IARC multicentric case-control
study. Lancet 2002;359(9312):1085–92.
2. Smith JS, Green J, Berrington dG, Appleby P, Peto J, Plummer M, Franceschi S, Beral V.
Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003;
361:1159-67.
cancer and hormonal contraceptives: collaborative reanalysis of individual data for
16,573 women with cervical cancer and 35,509 women without cervical cancer from 24
epidemiological studies. Lancet 2007;370:1609-1621.
Statement 4: The risk of squamous cell carcinoma increases in current smokers

with the number of cigarettes smoked per day and with younger age at starting
smoking. (Level II-2, Grade A)
Current smokers had a significantly increased risk of squamous cell carcinoma of the
cervix compared to never smokers (RR 1.60; 95% CI 1.48-1.73, p < 0.001). There was
increased risk for past smokers also, though to a lesser extent (RR 1.12; 95% CI 1.01-
1.25), and there was no clear trend with time since stopping smoking (p trend = 0.60).
There was no association between smoking and adenocarcinoma of the cervix (RR 0.89,
95% CI 0.74-1.06 and RR 0.89, 95% CI 0.72-1.10, for current and past smokers
respectively), and the differences between the RRs for smoking and squamous cell and
adenocarcinoma were statistically significant (current smoking p < 0.001 and past
smoking p = 0.01).1 A prospective study showed that smokers maintain cervical HPV
infections significantly longer and have a lower probability of clearing an oncogenic
infection than women who never smoked.2
Malignant transformation of HPV 16 immortalized human endocervical cells by cigarette

smoke condensate has been proven. The fact that nicotine and tobacco-specific
carcinogens have been detected in the cervical mucus of smokers further strengthens
the hypothesis of a synergistic action between cigarette smoking and HPV for the
development of high grade squamous intraepithelial neoplasia (HSIL)/cervical cancer.
Chemical tobacco-related carcinogens may exert a direct mitogenic effect causing DNA
damage.1
References:
1. International Collaboration of Epidemiological Studies of Cervical Cancer. Carcinoma of

the cervix and tobacco smoking: collaborative re-analysis of individual data on 13,541
women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix
from 23 epidemiological studies. Int J Cancer 2006;118:1481-1495.
2. Giulian AR, Sedjo RL, Roe DJ, Harri R, Baldwi S, Papenfuss MR, et al. Clearance of
oncogenic human papillomavirus (HPV) infection: effect of smoking. Cancer Causes
Control 2002;13:839-46.
Statement 5: Women who are co-infected with HPV and another sexually
transmitted agent, such as Chlamydia trachomatis or Herpes simplex virus 2
(HSV-2), are more likely to develop cervical cancer than are women who are not
co-infected. (Level II-2, Grade B)
Results from the IARC multicenter study found a 2-fold increase in risk of cervical cancer
when antibodies to C. trachomatis (OR 2.1; 95% CI 1.1-4.0) or to HSV-2 were present.1
A pooled analysis of 7 case-control studies examining the effect of HSV-2 infection in the
etiology of invasive cervical cancer found that among HPV DNA positive women, HSV-2
was associated with about a 3-fold increased risk of developing cervical cancer after
adjustment for potential confounders.2
References:
1. Smith JS, Munoz N, Herrero R, Eluf-Neto J, Ngelangel C, Franceschi S, et al. Evidence

for Chlamydia trachomatis as a human papillomavirus cofactor in the etiology of invasive
cervical cancer in Brazil and the Philippines. J Infect Dis 2002;185:324–31.
2. Smith JS, Herrero R, Bosetti C, et al. Herpes simplex virus-2 as a human papillomavirus
cofactor in the etiology of invasive cervical cancer. J of the NCI Nov 2002;94(21):1604–
1613.
Statement 6: Women infected with human immunodeficiency virus (HIV) are more
readily infected with high risk HPV types and are more likely to develop cervical
cancer than HIV-negative women in the same age category. (Levell III, Grade C)
A meta-analysis of data from 20 studies including nearly 5,600 subjects worldwide found
that 41% of HIV-positive women with HSIL had more than one type of HPV, compared
with 7% of women in the general population. Further, HIV-positive women with SIL were
less likely to have oncogenic HPV type 16, but more likely to have other high-risk types
such as 18, 51, 52, and 58.1
Several studies have shown that HIV-positive women are more likely than their HIV-
negative counterparts to develop cervical intraepithelial neoplasia (CIN). In the HIV
Epidemiology Research Study, women with HIV also had more vulvar, vaginal, and
perianal lesions. 2,3
References:
1. Clifford GM, Gonçalves MA, Franceschi S; HPV and HIV Study Group Human
papillomavirus types among women infected with HIV: a meta-analysis. AIDS 2006 Nov
28;20(18):2337-44.
2. Palefsky JM, Holly EA. Chapter 6: Immunosuppressionand co-infection with HIV. J Natl
Cancer Inst Monogr 2003;41-6.
3. Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients
with human immunodeficiency virus infection and acquired immunodeficiency syndrome.
J of the NCI 2000;92:1500-10.
Statement 7: Early age at first intercourse increases the risk for cervical cancer
(age < 14). (Level II-2, Grade A)
Supporting Statement:
The RR for age at first intercourse " 14 versus ! 25 years, conditioned on age, study,
and lifetime number of sexual partners was 3.52 (95% CI 3.04-4.08), which decreased to
2.05 (95% CI 1.54-2.73) after additional conditioning on reproductive factors.1
Reference:

carcinoma and sexual behaviour: collaborative reanalysis of individual data on 15,461
epidemiological studies. Cancer Epidemiol Biomarkers Prev 2009 Apr;18(4):1060-9.
Statement 8: The risk of invasive cervical carcinoma increased with lifetime

number of sexual partners (6 or more). (Level II-2, Grade B)
The risk of invasive cervical carcinoma increased with lifetime number of sexual partners
(p for linear trend <0.001). The RR for ! 6 versus 1 partner, conditioned on age, study,
and age at first intercourse, was 2.27 (95% CI 1.98-2.61) and increased to 2.78 (95% CI
2.22-3.47) after additional conditioning on reproductive factors.1
Reference:

carcinoma and sexual behaviour: collaborative reanalysis of individual data on 15,461
epidemiological studies. Cancer Epidemiol Biomarkers Prev 2009 Apr;18(4):1060-9.
Statement 9: Early age at first full term pregnancy (age < 17) increases the risk for
invasive cervical cancer. (Level II-2, Grade B)
Early age at first full term pregnancy is associated with risk of both invasive cervical
carcinoma and CIN 3/CIS. After controlling for number of full term pregnancies, the RR
for first full term pregnancy at age < 17 years compared with ! 25 years was 1.77 (95%
CI 1.42-2.23) for invasive cervical carcinoma, and 1.78 (95% CI 1.26-2.51) for CIN
3/CIS.1
Reference:

carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563
epidemiological studies. Int J Cancer 2006;119:1108-1124.
Statement 10: Male circumcision is associated with a reduced risk of penile HPV
infection and, in the case of men with a history of multiple sexual partners, a
reduced risk of cervical cancer in their current female partners. (Level II-2, Grade
B)
An analysis of pooled data on 1913 couples from seven case-control studies of CIS and
cervical cancer in five countries showed that circumcised men were less likely than
uncircumcised men to have HPV infection (OR 0.37; 95% CI 0.16-0.85). Monogamous
women whose male partners had six or more sexual partners and were circumcised had
a lower risk of cervical cancer than women whose partners were uncircumcised
(adjusted OR 0.42; 95% CI 0.23-0.79).1
Reference:
1. Castellsague X, Bosch FX, Munoz N, Meijer CJ, Shah KV, de Sanjose S, Eluf-Neto J,
Ngelangel CA, Chichareon S, Smith JS, Herrero R, Moreno V, Franceschi S. Male
circumcision, penile human papillomavirus infection, and cervical cancer in female
partners. N Engl J Med 2002; 346:1105-12.
Statement 11: The risk of developing invasive cervical cancer is three to ten times
greater in women who have not been screened. (Level II-2, Grade A)
Case-control studies have found that the risk of developing invasive cervical cancer is
three to ten times greater in women who have not been screened.1-3 Risk also increases
with long duration following the last normal Papanicolau (Pap) test, or similarly, with
decreasing frequency of screening.4
References:
1. Clarke EA, Anderson TW. Does screening by "Pap" smears help prevent cervical
cancer? A case-control study. Lancet 1979;2(8132):1-4.
2. La Vecchia C, Franceschi S, Decarli A, et al. "Pap" smear and the risk of cervical
neoplasia: quantitative estimates from a case-control study. Lancet 1984;2(8406):779-
82.
3. Herrero R, Brinton LA, Reeves WC, et al. Screening for cervical cancer in Latin America:
a case-control study. Int J Epidemiol 1992;21(6):1050-6.
4. Screening for squamous cervical cancer: duration of low risk after negative results of
cervical cytology and its implication for screening policies. IARC Working Group on
evaluation of cervical cancer screening programmes. Br Med J (Clin Res Ed)
1986;293(6548):659-64.
Statement 12: Low socio-economic status (SES) is recognized as a risk factor for
many health problems, including cervical cancer, particularly in low-resource
settings. (Level III, Grade C)
Women with low SES often have limited income, restricted access to health care
services, poor nutrition, and a low level of awareness about health issues and preventive
behavior. All of these factors can make them more vulnerable to illness and preventable
diseases such as cervical cancer.1
Reference:
1. Dos Santos IS, Beral V. Socio-economic differences in reproductive behaviour. IARC

Scientific Publications 1997;138:285–308.
III. PRIMARY PREVENTION
Statement 1: Total abstinence prevents HPV infection. (Level II-2, Grade A)
Among women who report no previous sexual intercourse, 0–8% have HPV infection
supporting the premise that the major route of transmission is sexual.1 The studies that
demonstrate genital HPV transmission by sexual intercourse and other genital contact
support the premise that abstaining from all genital contact, including non-penetrative
contact, is the most effective approach to preventing infection.2,3
References:
1. Fairley CK, Chen S, Tabrizi SN, Leeton K, Quinn MA, Garland SM. The absence of
genital human papillomavirus DNA in virginal women. Int J STD AIDS 1992;3(6):414-
417.
2. Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human
papillomavirus infection: incidence and risk factors in a cohort of female university
students. Am J Epidem 2003;157(3):218-226.
3. Herrero R, Hildesheim A, Bratti C, et al. Population-based study of human papillomavirus
infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 2000;92(6):464-
74.
Statement 2: Lifetime mutual monogamy prevents HPV infection. (Level II-2, Grade
A)
Because of the important role sexual contact plays in the transmission of genital HPV
infection the most effective personal prevention approach is to avoid contact with genital
HPV infection by limiting the number and type of sexual partners.1-3 The most important
factor that may decrease the likelihood that a woman is infected with genital HPV include
her having had a limited number of prior sex partners.1,2 The choice of partner is likely to
be important in the success of this approach because approximately 20% of women with
only one lifetime sex partner have HPV infection .4
References:
1. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal
papillomavirus infection in young women. N Engl J Med 1998;338(7):423-428.
2. Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human
papillomavirus infection: incidence and risk factors in a cohort of female university
students. Am J Epidemiol 2003;157(3):218-226.
3. Ley C, Bauer HM, Reingold A, Schiffman MH, Chambers JC, Tashiro CJ et al.
Determinants of genital human papillomavirus infection in young women. J Natl Cancer
Inst 1991; 83(14):997-1003.
4. Collins S, Mazloomzadeh S, Winter H, Blomfield P, Bailey A, Young LS et al. High
incidence of cervical human papillomavirus infection in women during their first sexual
relationship. BJOG 2002; 109(1):96-98.
Statement 3: Consistent and correct use of barrier protection decreases cervical
cancer incidence. (Level II-2, Grade A)
The RR of developing cervical cancer for consistent and correct use of barrier methods
of contraception is 0.4 (95% CI 0.2-0.9).1 Available clinical and epidemiologic data
indicate that genital HPV infection is transmitted by contact with infected skin or mucosa.
Laboratory studies have demonstrated that latex condoms provide an essentially
impermeable barrier to particles the size of HPV.2 Studies of HPV infection in men
demonstrate that most HPV infections are located on parts of the penis that would be
covered by a condom.3,4 However, even consistent and correct use of condoms would
not be expected to offer complete protection from HPV infection because infections also
may occur on sites not covered or protected by a condom. In men, HPV infection can
occur on the scrotum, groin area, base of the penis and anus.4 In women, HPV infection
can occur on the outside of the vulva, which can come into contact with the genital skin
of a man using a condom.3,4
References:
1. Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human
papillomavirus infection in young women. N Engl J Med 2006;354(25):2645-54.
2. Lytle CD, Routson LB, Seaborn GB, Dixon LG, Bushar HF, Cyr WH. An in vitro
evaluation of condoms as barriers to a small virus. Sexually Transmitted Diseases 1997;
24(3):161-164.
3. Parazzini F, Negri E, La Vecchia C, et al. Barrier methods of contraception and the risk of
cervical neoplasia. Contraception 1989;40(5):519-30.
4. Hildesheim A, Brinton LA, Mallin K, et al. Barrier and spermicidal contraceptive methods
and risk of invasive cervical cancer. Epidemiology 1990;1(4):266-72.
Statement 4: Vaccination against HPV 16/18 is efficacious against persistent HPV

infection and ! CIN 2+. (Level I, Grade A)
In the per-protocol population, efficacy against the first co-primary endpoint (disease or
infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, 4/1615 cases
in the vaccine group vs 41/1607 in the placebo group) and 83.1% (95% CI 50.6-95.8,
4/1601 cases vs 23/1579 cases) against the second co-primary endpoint (disease or
infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy
against the first co-primary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs
154/1883 cases) and against the second co-primary endpoint was 22.6% (95% CI -2.9 -
41.9, 90/1886 cases vs 115/1883 cases).1
Vaccine efficacy against CIN 2+ associated with HPV 16/18 was 92.9% (95% CI 79.9-
98.3). Vaccine efficacy against CIN 2+ irrespective of HPV DNA in lesions was 30.4%
(95% CI 16.4-42.1) in the total vaccinated cohort (TVC) and 70.2% (95% CI 54.7-80.9) in
the TVC-naive. Corresponding values against CIN 3+ were 33.4% (95% CI 9.1-51.5) in
the TVC and 87.0% (95% CI 54.9-97.7) in the TVC-naive.2
References:
1. Muñoz N, Manalastas R Jr, Pitisuttithum P. Safety, immunogenicity, and efficacy of

quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women
aged 24-45 years: a randomised, double-blind trial. Lancet 2009 Jun 6;373(9679):1949-
57.
2. Paavonen J, Naud P, Salmeron J, et al. Efficacy of human papillomavirus (HPV) 16/18
AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic
HPV types (PATRICIA): final analysis of a double-blind, randomised study in young
women. Lancet 2009 Jul 25;374(9686):301-14.
Statement 5: Oral supplementation with folic acid, beta carotene, or vitamin C

does not enhance regression of premalignant cervical lesions. (Level II-2, Grade
B)
Studies on oral supplementation with folic acid in CIN 1-2 women concluded that folic
acid does not enhance regression of early epithelial lesions.1 Clinical trials showed no
beneficial effect of oral supplementation with beta-carotene on regression of
preneoplastic lesions.2 There is no benefit of oral supplementation of vitamin C on early
lesion regression.3
References:
1. García-Closas R, Castellsagué X, Bosch X, González CA. The role of diet and nutrition
in cervical carcinogenesis: a review of recent evidence. Int J Cancer 2005 Nov
20;117(4):629-37.
2. Sasieni P. Chemoprevention of cervical cancer. Best Pract Res Clin Obstet Gynaecol
2006 Apr; 20(2):295-305
3. Ghosh C, Baker JA, et al. Dietary intakes of selected nutrients and food groups and risk
of cervical cancer. Nutr Cancer 2008;60(3):331-41.
IV. SECONDARY PREVENTION
Statement 1: Screening via regular gynecologic examinations and cytologic test

(Pap smear) with treatment of precancerous abnormalities decreases the
incidence and mortality of cervical cancer. (Level II-2, Grade A)
The Pap test has never been examined in a randomized controlled trial (RCT). A large
body of consistent observational data, however, supports its effectiveness in reducing
mortality from cervical cancer. Both incidence and mortality from cervical cancer have
sharply decreased in a number of large populations following the introduction of well-run
screening programs.1-2
A previous review estimated that the sensitivity of a single Pap test was 60-80% for high-
grade lesions, and even lower for low-grade lesions.3
References:
1. Sigurdsson K. Effect of organized screening on the risk of cervical cancer. Evaluation of

screening activity in Iceland 1964-1991. Int J Cancer 1993;54(4):563-70.
evaluation of cervical cancer screening programmes. Br Med J (Clin Res Ed)
1986;293(6548):659-64.
3. McCrory DC, Mather DB, Bastian L. Evaluation of Cervical Cytology: Evidence
Report/Technology Assessment No. 5. (Prepared by Duke University under Contract No.
290-97-0014.) AHCPR Publication No. 99-E010. Rockville, MD: Agency for Health Care
Policy and Research. February 1999. Available at
http://www.ahrq.gov/clinic/epcindex.htm. Accessed March 8, 2010.
Statement 2: Liquid based cytology offers the advantage of doing HPV testing on
the same preparation. However, it is not more sensitive or specific than
conventional pap smear. (Level II-2, Grade B)
Newer techniques that employ liquid based cytology (e.g., ThinPrep) have been
developed to improve the sensitivity of screening. As with the Pap test, the optimal
studies to determine the sensitivity and specificity of these technologies have not been
done. Some less-than-optimal studies show that sensitivity is modestly higher for
detecting any degree of CIN, with modestly lower specificity. A single study, however,
showed that conventional Pap testing was slightly more sensitive and specific than liquid
based cytology.1
The evidence is also mixed about whether liquid based techniques improve rates of test
adequacy. One advantage of liquid based cytology is that HPV testing (see below) can
be done on the same preparation. On the other hand, a disadvantage of liquid based
cytology is more expensive than conventional Pap testing. No study has examined
whether liquid based cytology actually reduces the number of women dying of cervical
cancer compared with conventional Pap testing.2
A meta-analysis of 8 studies identified by the authors to be methodologically sound

found no significant difference in sensitivity or specificity between the two technologies in
their ability to diagnose CIN 2 or higher using a cytology threshold of low grade
squamous intraepithelial neoplasia (LSIL) or HSIL. If the threshold for colposcopy was
lowered to atypical squamous cell of uncertain significance (ASC-US), however, the
liquid based cytology had a significantly lower specificity.3
References:
1. Hartmann KE, Hall SA, Nanda K, et al. Screening for Cervical Cancer. Rockville, Md:
Agency for Health Research and Quality, 2002.
2. Coste J, Cochand-Priollet B, de Cremoux P, et al. Cross sectional study of conventional
cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical
cancer screening. BMJ 2003;326(7392):733.
3. Arbyn M, Bergeron C, Klinkhamer P, Martin-Hirsch P,Siebers AG, Bulten J. Liquid
compared with conventional cervical cytology: a systematic review and meta-analysis.
Obstet Gynecol 2008; 111:167–77.
Statement 3: In low resource settings, visual inspection with acetic acid (VIA) is an
acceptable alternative to Pap smear. (Level I, Grade A)
A clustered RCT in rural India evaluated the impact of one-time VIA and immediate
colposcopy, directed biopsy, and cryotherapy (where indicated) on cervical cancer
incidence and mortality on healthy women aged 30 to 59 years. After 7 years of follow-
up, with adjustments for age, education, marital status, parity, and cluster design, there
was a 25% relative reduction in cervical cancer incidence in the intervention arm
compared with the control group (hazard ratio [HR] 0.75; 95% CI 0.55–0.95). Using the
same adjustments, cervical cancer mortality rates demonstrated a 35% relative
reduction in the intervention arm compared with the control group (HR 0.65; 95% CI,
0.47–0.89).1
An RCT of 6555 nonpregnant women, aged 35 to 65 years, recruited through community

outreach underwent screening using HPV DNA testing and VIA. Both screen-and-treat
approaches were found to be safe and the tests resulted in a lower prevalence of high-
grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and
12 months.2
References:
1. Sankaranarayanan R, Esmy PO, Rajkumar R, et al. Effect of visual screening on cervical

cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial. Lancet
2007;370(9585): 398-406.
2. Denny L, Kuhn L, De Souza M, et al. Screen-and-treat approaches for cervical cancer
prevention in low-resource settings: a randomized controlled trial. JAMA
2005;294(17):2173-81.
Statement 4: Screening should begin approximately 3 years after the onset of

vaginal intercourse but not earlier than 21. (Level II-2, Grade A)
Screening before age 21 should be avoided because it may lead to unnecessary and
harmful evaluation and treatment in women at very low risk of cancer. Young women
(16-20 years old) commonly become infected by HPV shortly after the initiation of
vaginal intercourse but, in most, they are cleared by the immune system within 1–2
years without producing neoplastic changes. No data demonstrate a benefit of screening
in women younger than 21 years in regard to future rates of CIN 2 and 3, or even that
screening women 20 to 24 years old reduces the rate of cervical cancer in women 30
years or younger.1-3
The 2005 World Health Organization-Western Pacific Regional Office (WHO-WPRO)

reported the mean age of sexual debut to be 14-15 years. In 2002, 23% of young adults
had engaged in premarital sex and the number steadily increased over the last decade.
An estimated 1.6 million young adults ages 15-27 years, or 34% of the country’s youth,
have had multiple sexual partners.4-5
References:
1. Moscicki AB, Shiboski S, Broering J, Powell K, Clayton L, Jay N, et al. The natural history
of human papillomavirus infection as measured by repeated DNA testing in adolescent
and young women. J Pediatr 1998;132:277–84.
2. Insinga RP, Dasbach EJ, Elbasha EH, Liaw KL, Barr E. Incidence and duration of
cervical human papillomavirus 6, 11, 16, and 18 infections in young women: an
evaluation from multiple analytic perspectives. Cancer Epidemiol Biomarkers Prev
2007;16:709–15.
3. Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population
based case-control study of prospectively recorded data. BMJ 2009;339:b2968.
4. Sexual and reproductive health of adolescents and youths in the Philippines: a review of
related literature and projects 1995-2003. Manila: World Health Organization-Western
Pacific Regional Office (WHO-WPRO) 2005.
5. Domingo E, Dy Echo A. Epidemiology, prevention and treatment of cervical cancer in the
Philippines. J Gynecol Oncol Mar 2009;20(1):11-16.
Statement 5: Annual screening with conventional cervical cytology smears, or
biennial screening using liquid based cytology, is recommended until age 30
years. At or after age 30 years, a woman who has had three consecutive,
technically satisfactory normal/negative for intraepithelial lesions or malignancy
cytology results may undergo screening every 2 to 3 years using either
conventional or liquid based cytology. (Level II-3, Grade A)
Studies over the past several decades have shown that in an organized program of
cervical cancer screening, annual cytology examinations offer little advantage over
screening performed at 2- or 3-year intervals.1-2
References:
1. Sawaya GF, McConnell KJ, Kulasingam SL, Lawson HW, Kerlikowske K, Melnikow J, et
al. Risk of cervical cancer associated with extending the interval between cervical cancer
screenings. N Engl J Med 2003;349:1501–9.
evaluation of cervical cancer screening programmes. Br Med J 1986;293:659–64.
Statement 6: Women aged 30 years and older who have had three consecutive
negative cervical cytology screening test results and who have no history of CIN 2
or CIN 3, are not HIV infected, are not immunocompromised, and were not
exposed to diethylstilbestrol in utero may extend the interval between cervical
cytology examinations to every 3 years. (Level I to II-2, Grade A)
British study of 4,012 women aged 20–69 years with invasive cancer showed that
whereas cytology screening in 3 years prior to diagnosis offered a 60% and 80%
reduction in the incidence of cervical cancer at ages 40 years and 64 years respectively,
screening between age 20 years and 24 years provided no significant reduction in
invasive cancer in women younger than 30 years.1
In a woman aged 30 years or older who is known to have multiple recent consecutive
negative cervical cytology test results, the risk of developing CIN 3 or cancer is low, and
screening at 3-year intervals is a safe, cost effective approach, with either conventional
or liquid based cytology.2
References:
1. Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population

based case-control study of prospectively recorded data. BMJ 2009;339:b2968.
2. Ronco G, Cuzick J, Pierotti P, Cariaggi MP, Dalla Palma P, Naldoni C, et al. Accuracy of
liquid based versus conventional cytology: overall results of new technologies for cervical
cancer screening: randomised controlled trial. BMJ 2007;335:28.
Statement 7: Women treated in the past for CIN 2-3 or gynecologic cancers remain
at risk for persistent or recurrent disease for at least 20 years after treatment and
after initial post treatment surveillance, and should continue to have annual
screening for at least 20 years. (Level II-2 to III, Grade B)
Women who had HSIL before hysterectomy can develop recurrent intraepithelial
neoplasia or carcinoma at the vaginal cuff years postoperatively.1-3 Overall observed
cumulative rates of CIN 2/3 in the first 6 years after treatment were 14.0% (95% CI
13.84-14.15%) for women originally treated for CIN 3, 9.3% (95% CI 9.09-9.42%) for
CIN 2, and 5.6% (95% CI 4.91-5.21%) for CIN 1.2 Annual rates of CIN 2/3 were less
than 1% after 6 years. Overall incidence of invasive cancer (per 100 000 woman-years)
was higher in the CIN cohort (37 invasive cancers, 95% CI 30.6-42.5 cancers) than in
the comparison cohort (6 cancers, 95% CI 4.3-7.7 cancers).2,3
References:
1. Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006
consensus guidelines for the management of women with cervical intraepithelial
neoplasia or adenocarcinoma in situ. 2006 American Society for Colposcopy and
Cervical Pathology-sponsored Consensus Conference. Am J Obstet Gynecol
2007;197:340–5.
2. Melnikow J, McGahan C, Sawaya GF, Ehlen T, Coldman A.Cervical intraepithelial
neoplasia outcomes after treatment: long-term follow-up from the British Columbia Cohort
Study. Natl J Cancer Inst 2009 May 20;101(10):721-8. Epub 2009 May 12
3. Stokes-Lampard H,Wilson S,Waddell C, Ryan A, Holder R, Kehoe S. Vaginal vault
smears after hysterectomy for reasons other than malignancy: a systematic review of the
literature. BJOG 2006;113:1354–65.
Statement 8: In women who have had a total hysterectomy for benign indications
and have no prior history of high grade CIN, routine cytology testing should be
discontinued. (Level II-2, Grade B)
A systematic review showed an aggregated data on 6,543 women from 19 studies that
had a hysterectomy in which the cervix was benign. On follow-up, among the women
with hysterectomy for benign indications, 1.8% had an abnormal cytology result and
0.12% had vaginal intraepithelial neoplasia (VAIN) on biopsy. There were no cases of
cancer.1
Reference:
1. Stokes-Lampard H,Wilson S,Waddell C, Ryan A, Holder R, Kehoe S. Vaginal vault

smears after hysterectomy for reasons other than malignancy: a systematic review of the
literature. BJOG 2006;113:1354–65.
Statement 9: Discontinue cervical cancer screening between 65 years and 70

years of age in women who have three or more negative cytology test results in a
row and no abnormal test results in the past 10 years. (Level II-2, Grade B)
Postmenopausal women with multiple prior consecutive negative cervical cytology test
results are at low risk for cervical cancer. In addition, mucosal atrophy common after
menopause may predispose to false-positive cytology. False-positive results are likely to
be followed with additional procedures, anxiety, and expense in this population.1
References:
1. Sawaya GF, Grady D, Kerlikowske K, Valleur JL, Barnabei VM, Bass K, et al. The
positive predictive value of cervical smears in previously screened postmenopausal
women: the Heart and Estrogen/progestin Replacement Study (HERS). Ann Intern Med
2000;133:942–50.
Statement 10: Co-testing using the combination of cytology plus HPV DNA testing
is an appropriate screening test for women older than 30 years. (Level II-3, Grade
A)
Pooled data from seven European studies were analyzed to compare co-testing using
HPV DNA plus cervical cytology with cytology alone in a total of 24,295 women. Any
low-risk woman aged 30 years or older who receives negative test results on both
cervical cytology screening and HPV DNA testing should be rescreened no sooner than
3 years subsequently. Co-testing is not recommended for women younger than 30 years
because of the very high prevalence of high-risk HPV infections in sexually active
women in this age group.1
The likelihood of testing HPV-positive in conjunction with co-testing is population specific

and depends on the age and risk behaviours in that population. The positive predictive
value of a single Pap-negative and HPV-positive co-test for CIN 3 or more severe
remains less than ideal. Thus, the development of a viable strategy for identifying the
subset of Pap-negative; HPV-positive women at highest risk of CIN 3 or more severe
would further improve the efficiency of secondary cervical cancer prevention.2
A consistently low six year cumulative incidence rate of CIN 3+ among women negative
for HPV suggests that cervical screening strategies in which women are screened for
HPV every six years are safe and effective. The study (Multinational cohort study with
joint database analysis) suggests that screening intervals could safely be lengthened to
six years among women with a negative result on an HPV test. This could at least partly
compensate for the increased referral rate resulting from HPV based screening
strategies.3
References:
1. Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, et al. Long term
predictive values of cytology and human papillomavirus testing in cervical cancer
screening: Joint European cohort study. Joint European Cohort Study. BMJ
2008;337:a1754.
2. Castle PE, Fetterman B, Poitras N, Lorey T, Shaber R, Kinney W. Five-year experience
of human papillomavirus DNA and Papanicolaou test cotesting. Obstet Gynecol 2009
Mar;113(3):595-600.
3. Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, de Sanjose S, Naucler
P, Lloveras B, Kjaer S, Cuzick J, van Ballegooijen M, Clavel C, Iftner T; Joint European
Cohort Study. Long term predictive values of cytology and human papillomavirus testing
in cervical cancer screening: joint European cohort study. BMJ 2008 Oct 13;337.
Statement 11: Testing for HPV DNA currently is used in cervical cancer screening
as a triage test to stratify risk to women aged 21 years and older with a cytology
diagnosis of ASC-US and postmenopausal women with a cytology diagnosis of
LSIL. (Level III, Grade B)
A recent review of 20 studies assessing the efficacy of HPV DNA testing to triage ASC-
US determined a sensitivity of 92.5% to detect CIN 2 or worse and 95.6% to detect CIN
3 or worse with specificities of 62.5% and 59.2%, respectively.1-2
References:
1. Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006
consensus guidelines for the management of women with abnormal cervical cancer
screening tests. 2006 American Society for Colposcopy and Cervical Pathology-
sponsored Consensus Conference. Am J Obstet Gynecol 2007;197:346–55.
2. Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. clinical applications of
HPV testing: a summary of meta-analyses. Vaccine 2006;24(suppl 3):S3/78–89.
Statement 12: Annual gynecologic examination is recommended regardless of the

frequency of screening. (Level III, Grade C)
Regardless of the frequency of cervical cytology screening, physicians also should

inform their patients that annual gynecologic examinations may still be appropriate even
if cervical cytology is not performed at each visit.1
Reference:
1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number

109, December 2009: cervical cytology screening. Obstet Gynecol 2009;114:1409-1420.
Statement 13: Women who have been immunized against HPV 16 and HPV 18
should be screened by the same regimen as nonimmunized women. (Level III,
Grade C)
If HPV immunization is widely implemented, it has been proposed that the impact in
terms of reduction in cervical cancer will not begin to be realized for another 15–20
years.1,2 In the meantime, secondary prevention, through a screening regimen of
cervical cytology with or without concomitant HPV DNA testing remains the best
approach to protecting women from cervical cancer.1
References:
1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number

109, December 2009: cervical cytology screening. Obstet Gynecol 2009;114:1409-1420.
2. Wright TC, Van Damme P, Schmitt HJ, Meheus A.Chapter 14: HPV vaccine introduction
in industrialized countries. Vaccine 2006;24(suppl 3):S3/122–31.
Statement 14: A Pap test should be obtained twice in the first year after diagnosis
of HIV infection and, if the results are normal, annually thereafter. (Level III, Grade
C)
Women infected with HIV are more readily infected with high-risk HPV types and are
more likely to develop precancerous lesions (and develop them more rapidly) than HIV-
negative women in the same age category.1-3
References:
1. 2006 CDC Guidelines on Sexually transmitted infections (MMWR Recommendations and

Reports, http://www.cdc.gov/std/treatment/2006 accessed april 29, 2010
2. De Sanjose S, Palefsky J. Cervical and anal HPV infections in HIV positive women and
men. Virus Research 2002 Nove;89(2):201–21.
3. Clarke B, Chetty R. Postmodern cancer: the role of human immunodeficiency virus in
uterine cervical cancer. Molecular Pathology 2002 Feb;55(1):19–24.
V. FIGO 2009 CLINICAL STAGING FOR CERVICAL CANCER
I The car cin o ma i s s tri ctl y c on fine d to th e c ervi x

IA I n va si ve car cin o ma that can b e di agn osed os ed onl y mi cr os co picall
pic all y, with
deep es estt i nv a sion o f < 5 mm an d l arge s t e x ten sio n o f < 7 mm
IA1 Me as ured str o mal in va sion o f < 3 mm in d epth a nd e xte n sion o f < 7
asured
mm
mm
IA2 Me as ured str o mal in va sion o f > 3 mm an d not > 5 mm
asured m m i n de p th an d
exten
ex ten sio n o f < 7 m m
IB Clini call y vi sibl e l esi on s li mi ted to th e cer vix u teri or sub clini cal
can ce rs gr eateaterer th an s tag e IA
IB1 C lini call y vi sibl e l esi on s < 4 c m
IB2 C lini call y vi sibl e l esi on s > 4 cmcm
II The car cin o ma ex te nd s be yon d the u teru s b u t ha s not e x ten ded to
exte
the pel vi c w all or to th e l o wer thi rd of the vagi na
wall
IIA Wi tho ut par a me trial in va sion
IIA1 C lini call y vi sibl e l esi on < 4 c m
IIA2 Clini call y vi sibl e l esi on > 4 cm
IIB Wi th ob vio us pa ra me trial in va sion
III The car cin o ma i nvol
nv ol ve s the lo wer third o f the va gina an d/or ca us es
hydr one phro si s or non fu nctioni
nc tioni ng ki dne y
IIIA Tu mo r in vol e s the lo wer third o f the vagi n a, wi th no e xten sio n to th e
pelvi c wall
IIIB E xten sio n to the
t he pel vi c wall a nd/or hy dron ephro si s or non fun c tioni ng
kidn ey
IV The car cin o ma ha s exte nded b eyond ey ond the true pel vis or h as clini call y
invol ve d the mu co sa o f th e bladd er or r e ctum.
ctum . A bullo us e de ma , as
su ch , doe s no t per mit a ca se allo tted to b e sta ge IV
IVA S prea d of gro wth
w th to
t o the a dja cen t orga ns
IVB S prea d to di st an t or gan s
stan
VI. MODIFIED WHO HISTOLOGICAL CLASSIFICATION OF CERVICAL TUMORS
A. EPITHELIAL TUMORS
1. Squamous cell carcinoma
a. Microinvasive squamous cell carcinoma
b. Invasive squamous cell carcinoma
c. Verrucous carcinoma
d. Warty (condylomatous) carcinoma
e. Papillary squamous cell (transitional) carcinoma
f. Lymphoepithelioma-like carcinoma
2. Adenocarcinoma
a. Mucinous adenocarcinoma
(i) Endocervical type
(ii) Intestinal type
(iii) Signet-ring type
b. Endometrioid adenocarcinoma
(i) Endometrioid adenocarcinoma with squamous metaplasia
c. Clear cell adenocarcinoma
d. Minimal deviation adenocarcinoma
(i) Endocervical type (adenoma malignum)
(ii) Endometrioid type
e. Serous adenocarcinoma
f. Mesonephric carcinoma
g. Well-differentiated villoglandular adenocarcinoma
3. Other epithelial tumors
a. Adenosquamous carcinoma
b. Glassy cell carcinoma
c. Mucopeidermoid carcinoma
d. Adenoid cystic carcinoma
e. Adenoid basal carcinoma
f. Carcinoid-like tumor
g. Small cell carcinoma
h. Undifferentiated carcinoma
B. MESENCHYMAL TUMORS & MIXED EPITHELIAL-MESENCHYMAL TUMORS

1. Leiomyosarcoma
2. Endocervical stromal sarcoma
3. Embryonal rhabdomyosarcoma
4. Alveolar soft-part sarcoma
5. Adenosarcoma
6. Malignant mixed mesodermal tumor (MMMT)
C. MISCELLANEOUS TUMORS
1. Primary malignant melanoma
2. Primary choriocarcinoma
3. Lymphoma
4. Leukemia
5. Primary germ cell tumor
VII. GENERAL GUIDELINES IN THE DIAGNOSIS AND MANAGEMENT OF

CERVICAL CANCER
1. Cervical cancer is diagnosed by biopsy1.

2. Cervical cancer is staged clinically.1
3. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done to rule
out invasion. Metastatic work-ups include renal imaging studies (IVP), liver function
tests, chest x-ray, and skeletal survey.1
4. Special diagnostic imaging studies may be done to guide treatment planning
include ultrasound, magnetic resonance imaging (MRI), computed tomography scan
(CT scan), positron emission tomography scan (PET Scan) and bone
scintigraphy.2,3 These imaging studies will not be part of the staging.
5. Concurrent chemotherapy and complete radiotherapy (chemoradiation) is the
standard of treatment.4-9
6. For patients who are unable to receive chemotherapy, radiation treatment alone may
be given.1
7. Adenocarcinomas have shown no significant difference in clinical behavior from
squamous cell carcinoma.17
References:
1. Benedet JL, Pecorelli, S, Hacker NF, Ngan HYS. Staging Classifications and Clinical
Practice Guidelines of Gynecologic Cancers by FIGO Committee on Gynecologic
rd
Oncology and IGCS Guidelines Committee, 3 edition, November 2006.
2. Hricak H, Gatsonis C, Chi DS, et al. Role of imaging in the pretreatment evaluation of
early invasive cancer: Results of the Intergroup Study American College of Radiology
Network 6651 Gynecologic Oncology Group 183. J Clinical Oncol 2005;23(36):9329-
9337.
3. Loft A, Berhelsen AK, et al. Diagnostic value of PET/CT in the evaluation of patients with
cervical cancer : A prospective study. Gynecol Oncol 2007;106: 29-34.
4. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of 5-fluorouracil plus
cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma
of the cervix with negative para-aortic lymph nodes: A Gynecologic Oncology Group and
Southwest Oncology Group Study. J Clin Oncol 1999;17:1339-1348.
5. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based chemotherapy and
radiotherapy for locally advanced cervical cancer. New Engl J Med 1999;340:1144-1153.
6. Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy
for bulky stage IB cervical carcinoma. New Engl J Med 1999;340:1154-1161.
7. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared
with pelvic and para-aortic radiation for high-risk cervical cancer. New Engl J Med 1999;
340:1137-1143.
8. Peters WAI, Liu PY, Barrett R, et al. Cisplatin, 5-fluorouracil plus radiation therapy are
superior to radiation therapy as adjunctive therapy in high risk, early stage carcinoma of
the cervix after radical hysterectomy and pelvic lymphadenectomy: Report of a phase III
intergroup study. Gynecol Oncol 1999;72:443.
9. Lehman M, Thomas G. Is concurrent chemotherapy and radiotherapy the new standard of
care for locally advanced cervical cancer? Int J Gynecol Cancer 2001;11:87-89.
th
10. Di Saia P and Creasman W. Clinical Gynecologic Oncology, 7 edition 2007
OVARIAN CANCER
I. INCIDENCE
! The overall incidence of epithelial ovarian cancer varies from 9 to 17/100,000.

This incidence rate increases proportionately with age. The largest number of
patients with epithelial ovarian cancer is in the age group 60-64.1
! An estimated 21,550 new cases were reported for 2009 representing 3% of all
new cancer cases in women in the United States. This is the ninth most common
cancer. An estimated 14,600 deaths were reported representing 5% of all the
female cancers and the fifth most lethal.2
! Cancer of the ovary is the tenth leading site for both sexes combined (3.1%) and
the fifth among women (6%). New cases for 2005 were estimated at 3,283 and
deaths at 1,918. Incidence rises steeply starting at age 40.3
References:
1. Benedet JL, Pecorelli S, Ngan HYS, and Hacker NF. Staging Classifications and Clinical
rd
Practice Guidelines for Gynaecological Cancers. FIGO and IGCS Collaboration, 3 ed.,
November 2006.
2. Jemal A, Siegel R, Ward E, Yongping H, Jiaquan X, and Thun MJ. Cancer statistics,
2009. CA Cancer J Clin 2009;59;225-249.
II. RISK FACTORS
Statement 1: A strong family history of either breast or ovarian cancer is the most
important risk factor for the development of epithelial ovarian cancer. (Level II-2,
Grade B)
Approximately 10 to 15% of all epithelial ovarian cancers have a hereditary

predisposition. This is seen most commonly within the breast-ovarian cancer family
syndrome because of mutations in BRCA1 or BRCA2. The lifetime risk of ovarian cancer
in women with a germline mutation in BRCA1 approaches 40%. In women with BRCA2
germline mutation, the lifetime risk ranges from 10 to 20%.1-3
A small number of families have been reported to have an excess of ovarian cancer but
not of breast cancer. They are called site-specific ovarian cancer families. This is also
linked to BRCA1 mutation.4
A second inherited disorder with an increased risk of ovarian cancer is the hereditary
non-polyposis colon cancer (HNPCC) syndrome or Lynch Syndrome II but this accounts
for only approximately 1% of all ovarian cancers. The cumulative incidence is 12%.5
References:
1. Pal T, Permuth-Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large
proportion of ovarian carcinoma cases. Cancer 2005;104:2807-2816.
2. Reedy M, Gallion H, Fowler JM, Kryscio R, Smith SA. Contribution of BRCA1 and
BRCA2 to familial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol
2002;85:255-259.
3. Antoniou A, Pharaoah PD, Narod S, et al. Average risks of breast and ovarian cancer
associated with BRCA1 and BRCA2 mutations detected in case series unselected for
family history: a combined analysis of 22 studies. Am J Hum Genet 2003 May;72:1117-
1130.
4. Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-
repair genes. Int J Cancer 1999;81:214-218.
5. Lindor NM, Petersen GM, Hadley DW, et al. Recommendations for the care of individuals
with an inherited predisposition to Lynch syndrome: a systematic review. JAMA
2006;296:1507-1517.
Statement 2: Ages at menarche and menopause are weak predictors of risk for
epithelial ovarian cancer. (Level II-3, Grade C)
Moderately elevated risks of epithelial ovarian cancer were reported among women
whose menarche occurred before 12 years of age compared to those who were older
than 14 but these were not significant.1-6
A positive association between age at natural menopause and epithelial ovarian cancer
risk appears in several case-control studies with risk estimates of 1.5-2.9 for the older
menopause categories compared to the younger ones. 7
Late age at menopause was also associated with increased risk of borderline ovarian
tumors in some studies but not in the others.7
References:
1. Booth M, Beral V, Smith P. Risk factors for ovarian cancer: a case-control study. Br J
Cancer 1989;60:592-598.
2. Franceschi S, La Vecchia C, Booth M, et al. Pooled analysis of 3 European case-control
studies of ovarian cancer: II. Age at menarche and at menopause. Int J Cancer
1991;49:57-60.
3. Hankinson SE, Colditz GA, Hunter DJ, et al. A prospective study of reproductive factors
and risk of epithelial ovarian cancer. Cancer 1995,76:284-290.
4. Kurian AW, Balise RR, McGuire V, Whittemore AS. Histologic types of epithelial ovarian
cancer: have they different risk factors? Gynecol Oncol 2005;96:520-530.
5. Riman T, Dickman PW, Nilsson S, et al. Risk factors of epithelial borderline ovarian
tumors: results of a Swedish case-control study. Gynecol Oncol 2001;83:575-585.
6. Harris R, Whittemore AS, Itnyre J. Characteristics relating to ovarian cancer risk;
collaborative analysis of 12 US case-control studies. III. Epithelial tumors of low
malignant potential in white women. Collaborative Ovarian Cancer Group. Am J
Epidemiol 1992;136:1204-1211.
7. Schildkraut JM, Cooper GS, Halabi S, Calingaert B, Hartge P, Whittemore AS. Age at
natural menopause and the risk of epithelial ovarian cancer. Obstet Gynecol 2001
Jul;98(1):85-90.
Statement 3: The use of fertility drugs does not increase the risk for ovarian
cancer. (Level II-2, Grade B)
In a pooled analysis of 8 case-control studies, among nulliparous, subfertile women,

neither any fertility drug use (Odds Ratio [OR] 1.60; 95% CI 1.91-3.74) nor more than 12
months of use (OR 1.54; 95% CI 0.45-5.27) was associated with ovarian cancer. Fertility
drug use in nulligravid women was associated with borderline serous tumors (OR 2.43;
95% CI 1.01-5.88) but not with any invasive histologic subtypes.1
Reference:
1. Ness RB, Cramer DW, Goodman MT, Kjaer SK, et al. Infertility, fertility drugs, and
ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol 2002 Feb
1;155(3):217-24.
Statement 4: Long-term use of unopposed estrogen or of estrogen plus progestin

is associated with increased ovarian cancer risk. (Level II-2, Grade B)
The National Institute of Health (NIH)-American Association of Retired Persons (AARP)

Diet and Health Study Cohort involving more than 97,000 women showed that the use of
unopposed estrogen for less than 10 years was not associated with ovarian cancer.
Unopposed estrogen for 10 years or more was associated with increased ovarian cancer
risk compared to never use (Relative Risk [RR] 1.89; 95% CI 1.22-2.95, p = 0.004; 56 vs
72 ovarian cancers per 100,000 person-years). Compared with no hormone replacement
therapy (HRT) use, 5 or more years of sequential HRT was associated with significantly
increased risk (RR 3.09; 95% CI 1.68-5.68, p < 0.001; 49 vs. 108 per 100,000 person-
years) of ovarian cancer.1
Reference:
1. Lacey JV Jr., Brinton LA, Leitzmann MF, Mouw T, Hollenbeck A, Schartzkin A, and
Harthe P. Menopausal hormone therapy and ovarian cancer risk in the national Institutes
of Health – AARP Diet and Health Study Cohort. J Natl Cancer Inst 2006;98:1397-405.
Statement 5: Endometriosis is linked to an increased risk of epithelial ovarian

cancer particularly the endometrioid and clear cell types. (Level II-3, Grade B)
Several studies have linked endometriosis to an increased risk of epithelial ovarian

cancer as much as 3-fold particularly the endometrioid and clear cell types. The risk
decreased in women who subsequently underwent ovarian surgery.1-2
The hormonal regulation of endometriosis may trigger a local inflammatory reaction. The
hyperestrogenism associated with the condition was positively related to the risk of
cancer development from endometriosis.3
References:
1. Brinton LA, Gridley G, Persson I, et al. Cancer risk after a hospital discharge diagnosis of
endometriosis. Am J Obstet Gynecol 1997,176:572-579.
2. Ogawa S, Kaku T, Amada S, et al. Ovarian endometriosis associated with ovarian
carcinoma: a clinicopathological and immunohistochemical study. Gynecol Oncol
2000,77:298-304.
3. Zanetta GM, Webb MJ, Li H, Keeney GL. Hyperestrogenism: a relevant risk factor for the
development of cancer from endometriosis. Gynecol Oncol 2000,79:18-22.
Statement 6: Pelvic inflammatory disease (PID) is positively associated with
epithelial ovarian cancer. (Level II-3, Grade C)
A number of studies have shown an increased risk of epithelial ovarian cancer after one
or more episodes of PID. The association was stronger if the PID occurred at an early
age, if the women were nulliparous, infertile, or had experienced recurrent PID
episodes.1-2
References:
1. Risch HA, Howe GR. Pelvic inflammatory disease and the risk of epithelial ovarian
cancer. Cancer Epidemiol Biomarkers Prev 1995;4:447-451.
2. Parazzini F, La Vecchia C, Negri E, et al. Pelvic inflammatory disease and risk of ovarian
cancer. Cancer Epidemiol Biomarkers Prev 1996;5:667-669.
Statement 7: The relationship between polycystic ovarian syndrome (PCOS) and

epithelial ovarian cancer is less extensively evaluated but points to an increased
risk. (Level II-3, Grade C)
Elevated risk of epithelial ovarian cancer appeared among women with PCOS (OR 2.5;
95% CI 1.1-5.9) and the association was stronger among those who had not used oral
contraceptive pills (OCPs) or were lean.1
Reference:
1. Schuldkraut JM, Schwingl PJ, Bastos E, et al. Epithelial ovarian cancer risk among
women with polycystic ovary syndrome. Obstet Gynecol 1996;88:554-559.
Statement 8: Adult obesity and obesity in early adulthood confer an increased risk
of ovarian cancer. (Level II-2, Grade B)
A systematic review and meta-analysis involving 16 population-based studies assessing

the association between overweight (body mass index [BMI] 25.0-29.9) and obesity (BMI
30) and histologically confirmed ovarian cancer showed that the pooled effect estimate
for adult obesity was OR 1.3 (95% CI 1.1-1.5) and a smaller increased risk for
overweight (OR 1.2; 95% CI 1.0-1.3). Nine studies on obesity in early adulthood showed
an increased risk of ovarian cancer. There was no evidence that the association varied
for the different histologic subtypes of ovarian cancer.1
Reference:
1. Olsen CM, Green AC, Whiteman DC, Sadeghi S, Kolahdooz F, and Webb PM. Obesity
and the risk of epithelial ovarian cancer: a systematic review and meta-analysis. Eur J
Cancer 2007 Mar; 43(4):670-709.
Statement 9: Current cigarette smoking increases the risk for the development of
mucinous epithelial ovarian cancer but not the other histologic types. (Level II-2,
Grade B)
A systematic review involving 8 population-based case-control studies, 1 pooled analysis

of case-control studies, and 1 cohort study for a total of 910 women with mucinous and
5,564 non-mucinous ovarian cancers showed a significant doubling of risk of mucinous
ovarian cancer in current smokers compared to never smokers (RR 2.1; 95% CI 1.7-2.7)
but no increased risk of serous (RR 1.0; 95% CI 0.8-1.2) or endometrioid (RR 0.8; 95%
CI 0.6-1.1), and a significant risk reduction for clear cell cancers (RR 0.6; 95% CI 0.3-
0.9). The risk of mucinous cancer increased with increasing amount smoked but
returned to that of never smokers within 20 to 30 years of stopping smoking.1
Reference:
1. Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM. Does smoking increase risk
of ovarian cancer? A systematic review. Gynecol Oncol 2006 Dec;103(3):1122-9.
Statement 10: There is no association between moderate alcohol intake and

ovarian cancer risk. (Level II-2, Grade B)
A pooled analysis of the primary data from 10 prospective cohort studies including more
than 500,000 women and with 2001 incident ovarian cancer cases showed no
association for intake of total alcohol (RR 1.12; 95% CI 0.86-1.44) or alcohol from wine,
beer or spirits and ovarian cancer risk. The association was not modified by OCP use,
HRT, parity, menopausal status, folate intake, BMI, or smoking. Associations for
endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings.1
Reference:
1. Genkinger JM, Hunter DJ, Spiegelman S, Anderson KE, et al. Alcohol intake and ovarian
cancer risk: a pooled analysis of 10 cohort studies. Br J Cancer 2006 Mar 13;94(5):757-
62.
Statement 11: A diet characterized by high meat and fat intake may increase the
risk of epithelial ovarian cancer. (Level II-2, Grade B)
A population-based case-control study done in Australia involving 683 women with

epithelial ovarian cancer and 777 control women aged 18 to 79 were investigated as to
their eating pattern: “snacks and alcohol”, “fruit and vegetable” and “meat and fat”. The
meat and fat pattern was associated with an increased risk of ovarian cancer (OR 2.49;
95% CI 1.75-3.55). Further adjustment for BMI strengthened this association. A diet high
in fruit and vegetables was not associated with reduced risk.1
A meta-analysis involving 8 observational studies with 6,689 subjects has shown an

increased risk with high total fat intake with an OR of 1.24-2.17.2
References:
1. Kolahdooz F, Ibiebele Tl, van der Pols JC, Webb PM. Dietary patterns and ovarian
cancer risk. Am J Clin Nutr 2009 Jan;89(1):297-304.
2. Huncharek M and Kupelnick B. Dietary fat intake and risk of epithelial ovarian cancer: a
meta-analysis of 6689 subjects from 8 observational studies. Nutrition and Cancer
2001;40:87-91.
Statement 12: There is no causal relationship between perineal talc use and
ovarian cancer. (Level II-2, Grade B)
Homogeneous data from 9 case-control studies showed a non-statistically significant

summary RR of 1.03 (95% CI 0.80-1.37) suggesting no association between talc-dusted
diaphragms and ovarian cancer development.1
Reference:
1. Huncharek M, Muscat J, Onitilo A, Kupelnic B. Use of cosmetic talc on contraceptive

diaphragms and ovarian cancer: a meta-analysis of nine observational studies. Eur J
Cancer Prev 2007;16:422-229.
Statement 1: Bilateral salpingo-oophorectomy (BSO) is the preventive measure of

choice for women with a known germline mutation in BRCA1 or BRCA2. (Level II-
2, Grade B)
BSO can decrease the risk of ovarian cancer by more than 90% in high risk group of
women with BRCA1 or BRCA2 germline mutations. Among BRCA1 carriers, BSO is
recommended at the age of 35 to 40 years as the incidence jumps from 2.3% to 6.5%
from age 40 to 45. Among BRCA2 carriers, ovarian cancers are diagnosed at a similar
age as those with sporadic cancers (1.2% incidence at age 50 to 4.1% at age 55), BSO
can be delayed safely until the patient is close to menopause.1-4
The decision to undergo risk-reducing BSO is highly personal. Risks and benefits must
be discussed with the patient including the impact of early menopause, the possible use
of hormonal replacement, and the emotional and psychological effects of the procedure.
Although BSO reduces the risk for ovarian cancer greatly, these mutation carriers can
still develop primary peritoneal cancer which develops in 4% to 5% of women even 20
years after BSO.3
References:
1. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prevention and observation of surgical
endpoints study group. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2
mutations. N Engl J Med 2002;346:1616-1622.
2. Kauff BD, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in
women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002 May 23;346:1609-1615.
3. Finch A, Beiner M, Lubinski J, et al. Hereditary ovarian cancer clinical study group.
Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in
women with BRCA1 or BRCA2 mutation. JAMA 2006;296:185-192.
4. Antoniou A, Pharaoah PD, Narod S, et al. Average risks of breast and ovarian cancer
associated with BRCA1 and BRCA2 mutations detected in case series unselected for
family history: a combined analysis of 22 studies. Am J Hum Genet 2003 May;72:1117-
1130.
Statement 2: Use of oral OCP confers long-term protection against ovarian cancer.
(Level II-2, Grade B)
A collaborative re-analysis of data from 45 epidemiological studies including 23,257

women with ovarian cancer and 87,303 controls showed that the longer the women had
used OCPs, the greater the reduction in ovarian cancer risk (p < 0.0001). This reduction
in risk persisted for more than 30 years after OCP use has ceased but with attenuation
over time (5 years from use 29% [95% CI, 23-34%]; 10-19 years from use 19% [95% CI
14-24%]; 20-29 years from use 15% [95% CI 9-21%]). The incidence of mucinous
tumors seemed little affected by OCPs.1
Reference:
1. Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R,

Hermon C, et al. Ovarian cancer and oral contraceptives: collaborative reanalysis of data
from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303
controls. Lancet 2008 Jan 26;371(9609):303-14.
Statement 3: Analgesics such as aspirin, nonsteroidal anti-inflammatory agents

(NSAIDs), and acetaminophen are potential chemopreventive agents for ovarian
cancer. (Level III, Grade C)
Preclinical investigations have provided evidence that aspirin and other NSAIDS can
inhibit the carcinogenesis of epithelial tumors including ovarian. This is thought to arise
primarily from inhibition of cyclo-oxygenase-2. There is also a link between cyclo-
oxygenase-2-mediated prostaglandin production and estrogen biosynthesis via the
aromatase enzyme. Given though the conflicting data from clinical observational studies,
it is too early to suggest the regular use of these drugs as a way of preventing ovarian
cancer.1
Reference:
1. Crew KD and Neugut AI. Aspirin and NSAIDS: effects in breast and ovarian cancers.
Curr Opin Obstet Gynecol 2006 Feb;18(1):71-5.
Statement 4: Increasing parity reduces the risk of epithelial ovarian cancer. (Level
II-2, Grade B)
From a pooled analysis of 12 United States-based case-control studies, an OR for

epithelial ovarian cancer of 0.32 (95% CI 0.18-0.56) was reported among women who
had given birth to five or more children compared to nulliparas. There was a 40% lower
risk after the first birth while each additional birth incurred another 14% risk reduction.1
Parous women also seem to be at reduced risks of borderline ovarian tumors although
the protection seems to be weaker than that seen for epithelial ovarian cancer.2
References:
1. Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk;

collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian
cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol
1992;136:1184-1203.
2. Harris R, Whittemore AS, Itnyre J. Characteristics relating to ovarian cancer risk;
collaborative analysis of 12 US case-control studies. III. Epithelial tumors of low
malignant potential in white women. Collaborative Ovarian Cancer Group. Am J
Epidemiol 1992;136:1204-1211.
Statement 5: Lactation confers protection against ovarian cancer risk most

significant with duration of 18 months or more. (Level II-2, Grade B)
From two prospective cohorts of the Nurses’ Health Study I and II of 16 years follow up
(total population of 149,693), it was found that ever breastfeeding was associated with a
non-significant reduction in ovarian cancer risk compared with never breastfeeding (RR
0.86; 95% CI 0.46-0.96) with a median duration of breastfeeding of nine months.
Duration of breastfeeding 18 months or more further decreases the ovarian cancer risk
compared to never breastfeeding (RR 0.66; 95% CI 0.97-1.00). For each month of
breastfeeding, the relative risk is decreased by 2% (RR 0.98; 95% CI 0.97-1.00).1
Reference:
1. Danforth KN, Tworoger SS, Hecht JL, Rosner BA, Colditz GA, and Hankinson SE.
Breastfeeding and ovarian cancer risk cancer in two prospective cohorts. Cancer Causes
Control. 2007 Jun; 18(5):517-23.
Statement 6: Tubal ligation confers a reduction in the risk for ovarian cancer.
From a prospective cohort study involving 121,700 nurses and 12 years of follow up,
there was a strong inverse relation between tubal ligation and ovarian cancer (RR 0.33;
95% CI 0.16-0.64). Hysterectomy also confers protection but to a less degree than tubal
ligation (RR 0.67; 95% CI 0.45-1.0).1
From a more recent population-based cohort study involving more than 65,000 women
who had tubal sterilization, the overall risk of ovarian cancer was decreased
(Standardized incidence ratio [SIR] 0.82; 95% CI 0.6-1.0) and was still decreased more
than 10 years after (SIR 0.65; 95% CI 0.5-1.0).2
References:
1. Hankinson SE, Hunter DJ, Colditz GA, Willett WC, Stampfer MJ, Rosner B, Hennekens
CH, and Speizer FE. Tubal ligation, hysterectomy, and risk of ovarian cancer. A
prospective study. JAMA. 1993 Dec 15;270(23):2813-8.
2. Kjaer SK, Mellemkjaer L, Brinton LA, Johansen C, Gridley G, and Olsen JM. Tubal
sterilization and risk of ovarian, endometrial and cervical cancer. A Danish population-
based follow-up of more than 65,000 sterilized women. Int J Epidemiol 2004;33:596-602.
Statement 7: Carotenoids significantly protect against ovarian cancer, either as

food or supplements. (Level II-2, Grade B)
A reduced risk of ovarian cancer related to carotenoid intake was demonstrated with an
OR of 0.33-0.64 for women with the highest compared to the lowest intake.1-2
References:
1. McCann SE, Moysich KB, Mettlin C. Intakes of selected nutrients and food groups and
risk of ovarian cancer. Nutr Cancer 2001;39:19-28.
2. McCann SE, Freudenheim JL, Marshall JR, Graham S. Risk of human ovarian cancer is
related to dietary intake of selected nutrients, phytochemicals, and food groups. J
Nutrition 2003;133: 1937-1942.
Statement 8: The consumption of tea may reduce the risk of epithelial ovarian
cancer. (Level II-3, Grade C)
Results from studies looking at caffeine intake have been inconsistent with some studies
showing an increased risk and others showing no risk or a reduced risk.1-2
Green and black tea have been shown to reduce the risk of epithelial ovarian cancer in a
dose-response manner. Based on a Swedish cohort study involving more than 61,000
women, tea consumption was inversely associated with the risk of ovarian cancer.
Compared with women who never or seldom consumed tea, the multivariate hazard
ratios (HR) for those who consumed less than 1 cup per day, 1 cup per day, and 2 or
more cups per day were 0.82 (95% CI 0.62-1.08), 0.76 (95% CI 0.56-1.04) and 0.54
(95% CI 0.31-0.91), respectively. Each additional cup of tea per day was associated with
an 18% lower risk of ovarian cancer (HR 0.82; 95% CI 0.68-0.99).3
References:
1. Larsson SC and Wolk A. Coffee consumption is not associated with ovarian cancer
incidence. Cancer Epidemiol Biomarkers Prev 2005;14:2273-2274.
2. Jordan SJ, Purdie DM, Green AC, and Webb PM. Coffee, tea, and caffeine and risk of
epithelial ovarian cancer. Cancer Causes Control 2004;15:359-365.
3. Larsson SC and Wolk A. Tea consumption and ovarian cancer risk in a population-based
cohort. Arch Intern Med 2005;165:2683-2686.
Statement 9: Recreational physical activity confers at best a weak to modest

protection against epithelial ovarian cancer. (Level II-2, Grade B)
Based on a meta-analysis involving 12 studies, summary estimates were 0.79 (95% CI

0.70-0.85) for case-control studies and 0.81 (95% CI 0.57-1.17) for cohort studies for the
risk of ovarian cancer associated with highest versus lowest levels of recreational
physical activity. Evidence is less consistent for occupational activity, vigorous activity,
and sedentary behavior.1
Reference:
1. Olsen CM, Bain CJ, Jordan SJ, Nagle CM, Green AC, Whiteman DC, Webb PM.
Recreational physical activity and epithelial ovarian cancer: A case-control study,
systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev
2007;16(11):2321-30.
Statement 1: For the general population, there is no evidence yet to support

routine screening for ovarian cancer using pelvic examination, CA-125, and
transvaginal ultrasound (TV-UTS). (Level I, Grade A)
Both the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) Study and the
Prostate, Lung Cancer, Colorectal Cancer, Ovarian (PLCO) Trial have not yet shown
that the effect of screening has resulted in decreased mortality for ovarian cancer.1-2
In the PLCO Trial, women were randomly assigned to either screening (annual pelvic
exam, TV-UTS, and CA-125) or no screening. The published prevalence data showed
31 women operated on for every invasive cancer detected and a high proportion of
advanced stage cancers. The true effectiveness of the screening strategy will be tested
by its ability to detect new cancers during the next several years.1
In the UKCTOCS Study, the combination of CA-125 and TV-UTS (multimodality screen)
resulted in higher specificity at 99.8% (versus 98.2%, p < 0.0001) compared to
ultrasound alone. The authors conclude that the two screening strategies are feasible.
The effect of both on mortality reduction is still to be determined.2
References:
1. Buys SS, Partridge E, Greene MH, et al. PLCO Project Team. Ovarian cancer screening
in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial: findings from
the initial screen of a randomized trial. Am J Obstet Gynecol 2005;193:1630-39.
2. Nicola Pocock. Preliminary results from the UK Collaborative Trial of Ovarian Cancer
Screening (UKCTOCS). The Lancet Oncology 2009;10(4): 327-340.
Statement 2: Although there is the lack of evidence for routine screening among
BRCA mutation carriers who have not undergone risk-reducing BSO, carriers are
advised semi-annual screening using pelvic examination, TV-UTS, CA-125, or their
combination. (Level III, GPP)
There are data that annual TV-UTS and CA-125 are not effective strategies for
screening for ovarian cancer in high risk women. There are limited data regarding the
effectiveness of a six month screening interval, thus until such data are available it is
reasonable to consider this approach in high risk women, especially in the context of a
clinical research setting.1
Reference:
1. NCCN Clinical Practice Guidelines in Oncology. Hereditary breast and/or ovarian

cancer.v.1.2010. www.nccn.org.
V. FIGO SURGICAL STAGING FOR OVARIAN CANCER
I Gro wtwthh li mi ted to th e o varie s

IA One o var y; n o a sci te s; capc ap s ule in ta ct; no tumor on e xter nal s urfac e
IB Two
T wo o varie s; no asci te s; cap sul e i nta c t; n o tu mor on e xtern al sur fa ce
IC One or bo th o varie s with ru ptured cap sul e , sur fa ce tu mor , p osi ti ve
as cites,
ascit es , or po siti ve p eritone al wa shi ng s
II Pelvi c e xten
xt en sion
IIA In v ol ve me nt o f u ter us or fallo pian tube s
IIB In vol ve me nt o f o th er pel vic tis su es
tissu
IIC Sta ge IIAI IA or I IB wi th ru ptu red c ap sule , sur fa ce tu mor, po si ti ve
as cites,
ascit es , or po siti ve p eritone al wa shi ng s
III Peritone
Perit one al i mp lan ts o ut sid e the pel vi s or p osi tiv e r etr operi to n eal or
inguin al l ymp h n ode s
IIIA Gro ssl y li mit ed to t he tr ue pel vi s wi th mi cr os copi c s eedi ng of
abdo mi nal peri ton eu m
IIIB I mpla nt s on abd o minal p eri tone u m " 2 c m in di a meter
III C I mpla nt s on abd o minal p eritone u m > 2 cm in di a meter or po siti ve
retro peri ton eal or i ngui nal ly mph nod es
IV Di st ant me ta sta se s; par en ch y mal liv er metasta se s
VI. WHO HISTOLOGICAL CLASSIFICATION OF OVARIAN TUMORS
A. SURFACE EPITHELIAL-STROMAL TUMORS

1. Serous tumors
a. Borderline malignancy (of low malignant potential)
(i) Cystic tumor and papillary cystic tumor
(ii) Surface papillary tumor
(iii) Adenofibroma and cystadenofibroma
b. Malignant
(i) Adenocarcinoma, papillary adenocarcinoma, and
papillary cystadenocarcinoma
(ii) Surface papillary adenocarcinoma
(iii) Adenocarcinofibroma and cystadenocarcinofibroma
(malignant adenofibroma and cystadenofibroma)
2. Mucinous tumors, endocervical-like and intestinal types
(i) Cystic tumor
(ii) Adenofibroma and cystadenofibroma
b. Malignant
(i) Adenocarcinoma and cystadenocarcinoma
(ii) Adenocarcinofibroma and cystadenocarcinofibroma
3. Endometrioid tumors
(i) Cystic tumor
(ii) Cystic tumor with with squamous differentiation
(iii) Adenofibroma and cystadenofibroma
(iv) Adenofibroma and cystadenofibroma with squamous
differentiation
b. Malignant
(i) Adenocarcinoma and cystadenocarcinoma
(ii) Adenocarcinoma and cystadenocarcinoma with
squamous differentiation
(iii) Adenocarcinofibroma and cystadenocarcinofibroma
(iv) Adenocarcinofibroma and cystadenocarcinofibroma with
squamous differentiation (malignant adenofibroma and
cystadenofibroma with squamous differentiation)
c. Epithelial-stromal and stromal
(i) Adenosarcoma, homologous and heterologous
(ii) Mesodermal (mullerian) mixed tumor (carcinosarcoma),
homologous and heterologous
(iii) Stromal sarcoma
4. Clear cell tumors
(i) Cystic tumor
(ii) Adenofibroma and cystadenofibroma
b. Malignant
(i) Adenocarcinoma
(ii) Adenocarcinofibroma and cystadenocarcinofibroma
5. Transitional cell tumors
a. Brenner tumor of borderline malignancy (proliferating)
b. Malignant Brenner tumor
c. Transitional cell carcinoma (non-Brenner type)
7. Mixed epithelial tumors (specific types)
b. Malignancy
8. Undifferentiated carcinoma and unclassified tumors
a. Undifferentiated carcinomas
b. Adenocarcioma, not otherwise specified
B. SEX CORD-STROMAL TUMORS

1. Granulosa-stromal cell tumors
a. Granulosa cell tumor group
(i) Adult granulosa cell tumor
(ii) Juvenile granulosa cell tumor
b. Thecoma-fibroma group
(i) Fibrosarcoma
(ii) Stromal tumor with minor sex cord elements
(iii) Signet-ring stromal tumor
(iv) Unclassified
2. Sertoli-stromal cell tumors
a. Sertoli-leydig cell tumor group (androblastoma)
(i) Well differentiated
(ii) Of intermediate differentiation
(iii) Poorly differentiated
(iv) Retiform
b. Sertoli cell tumor
c. Stromal-leydig cell tumor
3. Sex cord-stromal tumors of mixed or unclassified cell types
a. Sex cord tumor with annular tubules
b. Gynandroblastoma
c. Sex cord-stromal tumor unclassified
4. Steroid cell tumors
a. Leydig cell tumor group
(i) Hilus cell tumor
(ii) Leydig cell tumor, non-hilar type
(iii) Leydig cell tumor, not otherwise specified
b. Steroid cell tumors, not otherwise specified
(i) Well differentiated
(ii) Malignant
C. GERM CELL TUMORS

1. Primitive germ cell tumors
a. Dysgerminoma
b. Yolk sac tumor
c. Embyronal carcinoma
d. Polyembryoma
e. Nongestational choriocarcinoma
f. Mixed germ cell tumor (specify components)
2. Biphasic or triphasic teratoma - Immature teratoma
3. Monoendomermal teratoma and somatic type tumors associated with
dermoid cyst
a. Carcinoid group
(i) Insular
(ii) Trabecular
(iii) Mucinous
(iv) Strumal carcinoid
(v) Mixed
b. Neuroectodermal tumor group
(i) Ependymoma
(ii) Primitive neuroectodermal tumor
(iii) Medulloepithelioma
(iv) Glioblastoma multiforme
c. Carcinoma group
(i) Squamous cell carcinoma
(ii) Adenocarcinoma
(iii) Others
d. Melanocytic group
e. Sarcoma group
f. Sebaceous tumor group
g. Pituitary-type tumor group
h. Retinal anlage tumor group
i. Others
D. GERM CELL SEX CORD-STROMAL TUMORS

1. Gonadoblastoma
2. Mixed germ cell-sex cord-stromal tumor
E. TUMORS OF THE RETE OVARII

1. Adenocarcinoma
F. MISCELLANEOUS TUMORS
1. Small cell carcinoma, hypercalcemia type
2. Small cell carcinoma, pulmonary type
3. Large cell neuroendocrine carcinoma
4. Hepatoid carcinoma
5. Primary ovarian mesothelioma
6. Wilms tumor
7. Gestational choriocarcinoma
8. Adenoid cystic carcinoma
9. Basal cell tumor
10. Ovarian wolffian tumor
11. Paraganglioma
12. Myxoma
13. Soft tissue tumors not specific to the ovary
14. Others
G. LYMPHOID AND HEMATOPOETIC TUMORS

1. Malignant lymphoma
2. Leukemia
3. Plasmacytoma

OVARIAN CANCER
1. Symptoms of ovarian cancer are fairly nonspecific and often occur after the disease
has spread throughout the abdominal cavity.1
2. The presence of a pelvic mass at physical examination is the most important sign of
ovarian cancer.1
3. Gray-scale TV-UTS remains the standard for the evaluation of adnexal masses. The
addition of color Doppler studies makes it even more useful in predicting the
diagnosis of adnexal masses.2
4. The accuracy of CA 125 in the diagnosis of ovarian tumors is high and is very
important in the preoperative evaluation of adnexal masses.3
5. The addition of the biomarker HE4 to CA 125 has improved the sensitivity and
specificity over CA 125 alone for the risk assessment of a malignancy in patients with
a pelvic mass. As a single tumor marker, HE4 has a sensitivity of 64.2% at a
specificity of 98%. Combining CA 125 and HE4 is a more accurate predictor of
malignancy than either alone (sensitivity of 71.6% at specificity of 98%).4
6. Cancer of the ovary is staged surgically. The basis for the staging is the 2009 FIGO
Ovarian Cancer Staging, which is the same as the 1988 Staging Classification.5
7. The guidelines for complete surgical staging of ovarian cancer include:6,7
a. Systematic abdominal exploration via a midline incision.
b. Sampling of washings of four areas of the peritoneal cavity: diaphragm, right
and left hemiabdomen, pelvis.
c. Careful inspection and palpation of all peritoneal surfaces.
d. Biopsy and resection of any suspicious lesions, masses, and adhesions.
e. Total abdominal hysterectomy plus bilateral salpingo-oophorectomy.
f. Unilateral salpingo-oophorectomy with frozen section is permitted in young
patients with stage IA disease wanting to retain their fertility.
g. Infracolic omentectomy. For gross omental involvement, total omentectomy
or infragastric omentectomy should be performed.
h. Random biopsies of normal peritoneal surfaces, 2 samples from each of the
following: undersurface of the right hemidiaphragm, bladder reflection, cul-
de-sac, right and left paracolic recesses, and pelvic sidewalls.
i. Pelvic and para-aortic lymph node sampling. Systematic lymphadenectomy is
recommended for early stage and optimally debulked advanced ovarian
cancer.
j. For mucinous tumors or other types of ovarian tumors with the appendix
grossly involved with tumor, appendectomy must be performed.
8. Optimal debulking in ovarian cancer is complete resection with zero residual. The
hazard reduction with complete resection versus any residual tumor is 66% for
progression-free survival and 68% for overall survival.8
9. The standard frontline adjuvant chemotherapy for epithelial ovarian cancer is the
combination of paclitaxel and carboplatin.9, The addition of targeted therapy
bevazicumab with a maintenance phase shows promise with longer progression-free
survival.10
References:
1. Aletti GD, Gallenberg MM, Cliby WA, Jatoi A, Hartmann LC. Current management
strategies for ovarian cancer. Mayo Clin Proc 2007;82(6):751-770.
2. Medeiros LR, Rosa DD, da Rosa MI, Bozzetti MC. Accuracy of ultrasonography with
color Doppler in ovarian tumor: a systematic quantitative review. Int J Gynecol Cancer
2009 Feb;19(2): 230-6.
3. Medeiros LR, Rosa DD, da Rosa MI, and Bozzetti MC. Accuracy of CA 125 in the
diagnosis of ovarian tumors: a quantitative systematic review. Eur J Obstet Gynecol
Reprod Biol 2009 Feb; 142(2):99-105.
4. Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, et al. The use of multiple nover
tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass.
Gynecol Oncol 2008;108:402-8.
5. FIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the
vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynecol
Obstet 2009;105:3-4.
6. Benedet JL, Pecorelli S, Ngan HYS, and Hacker NF. Staging classifications and clinical
rd
practice guidelines for gynaecological cancers. FIGO and IGCS Collaboration, 3 ed.,
November 2006.
7. Society of Gynecologic Oncologists of the Philippines, Inc. Clinical Practice Guidelines,
th
5 ed. August 2008.
8. Du Bois A, Reuss A, Pujade-Luaraine E, Harter P, Rey-Coquard I, Pfisterer J. Role of
surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined
exploratory analysis of 3 prospectively randomized phase 3 multicenter trials. Cancer
2009;115:1234-44.
9. Ozols RF, Nundy BN, Greer BE, Fowler JM, Clarke-Pearson D, et al. Gynecologic
oncology group (2003) phase III trial of carboplatin and paclitaxel compared with cisplatin
and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic
Oncology Group study. J Clin Oncol 2003;21:3194-3200.
10. GOG 218 as presented in the ASCO Meeting June 4-8, 2010.Bevacizumab prolongs
progression-free survival in women with advanced ovarian cancer.
ENDOMETRIAL CANCER
!
I. INCIDENCE
• Endometrial cancer is the 3rd most common genital tract malignancy in the
Philippines, next to cervical and ovarian cancer. According to the 2005 Philippine
Cancer Facts and Estimates, it ranks 15th among malignancies affecting both
sexes and 9th among females.1
• The median age of diagnosis is 61 years, with most women diagnosed between
the age of 50 and 60 years. Ninety percent of cases occur in women over 50
years of age. Approximately 20% will be diagnosed before menopause and
approximately 5% of women will develop disease before the age of 40 years.2
• Based on worldwide statistics, the most common type of endometrial cancer
generally presents at an early stage of the disease. Seventy-two percent are at
stage I, 12% are stage II, 13% are stage III and 3% are stage IV at the time of
diagnosis.2 However, according to the Annual Statistics of the Section of
Gynecologic Oncology of the Philippine General Hospital for the past 3 years,
only 47% would present in the stage I disease, 19% in stage II, 23% in stage III
and 11% in stage IV.3
References:
2. Soroski JI. Endometrial cancer. Obstet Gynecol 2008;111:436-47.
3. Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Philippine
General Hospital Annual Statistics 2007-2009.
II. RISK FACTORS
Statement 1: Unopposed estrogen therapy substantially increases the risk of

endometrial cancer 2- to 10-fold, and this increased risk persists for several years
after discontinuation of estrogen use. (Level I, Grade A)
A meta-analysis of 30 studies on the association of unopposed estrogen and risk of

developing endometrial cancer was conducted. The summary relative risk (RR) was 2.3
for estrogen users compared to nonusers (95% CI 2.1-2.5). RR goes up to 9.5 for
estrogen use ! 10 years. The summary RR of endometrial cancer remained elevated
even after 5 or more years of discontinuation of unopposed estrogen therapy (RR 2.3).1
Women with an intact uterus should avoid using pure estrogen replacement therapy.
Instead, the combined hormone replacement therapy should be used, after adequate
screening for breast cancer, to reduce their risk for endometrial hyperplasia and
endometrial cancer.2
References:
1. Grady D, Gebretsadik T, Kerlikowske K, et al. Hormone replacement therapy and

endometrial cancer risk: a meta-analysis. Obstet Gynecol 1995;85:304-313.
2. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong
life in postmenopausal women. Ann Intern Med 1992;117:1016-1037.
Statement 2: Women treated with Tamoxifen for > 2 years have a statistically
significant increased risk of endometrial cancer. (Level II-2, Grade B)
Women who received Tamoxifen had a RR 2.53 (95% CI 1.35-4.97) greater risk of
developing an invasive endometrial cancer compared to non-users, with an average
annual rate of 2.30 per 1000 among users and 0.91 in the non-users. The increased risk
was predominantly in women 50 years of age or older. The RR of women aged 49 years
or younger was 1.21 (95% CI 0.41- 3.60), whereas it was 4.01 (95% CI 1.70-10.90) in
women aged 50 years or older. Through 66 months of follow-up, the cumulative
incidence was 5.4 per 1000 women and 13.0 per 1000 women in the non-user and user
groups, respectively.1
Women treated with Tamoxifen had a greater risk of endometrial cancer than those who
did not take Tamoxifen (OR 1.52; 95% CI 1.07-2.17). Risk increased 18% per year of
use and was statistically significantly elevated among women who were treated with
Tamoxifen for more than 2 years. 2
Among women taking Tamoxifen, cumulative dose and duration of use were highly
correlated (Pearson r 4.99 for case patients and r 4.97 for control subjects). Therefore,
the risk estimates for cumulative dose are similar to those for duration of therapy.2
References:
1. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer:
report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl
Cancer Inst 1998; 90:1371-1388.
2. Bernstein L, Deapen D, Cerhan JR, et al. Tamoxifen therapy for breast cancer and
endometrial cancer risk. J Natl Cancer Inst 1999;91:1654-1662.
Statement 3: Obesity predisposes to 2- to 4-fold relative risk of endometrial

Body mass index (BMI) was associated with a risk of endometrial cancer. Compared
with having a low BMI, being overweight was associated with an odds ratio (OR) of 1.60
(95% CI 1.23-2.08), and obesity was associated with an almost 4-fold increase in risk
(OR 3.88; 95% CI 3.11-4.85).1
Control or prevention of obesity could play a role in the primary prevention of

endometrial cancer. However, there are no outcome studies or recommendations from
major medical organizations about the effectiveness of this approach.2
References:
1. Shoff SM, Newcomb PA. Diabetes, body size, and risk of endometrial cancer. Am J
Epidemiol 1998;148:234-240.
2. Buchanan EM, Weinstein LC, Hillson C. Endometrial cancer. Am Fam Physician 2009;
80(10):1075-80.
Statement 4: Nulliparity confers an approximately 2-fold risk of developing
endometrial cancer compared with parity of one or more. (Level II-2, Grade B)
Compared with nulliparous women, parous women had a 30% lower risk of endometrial
cancer.1
In comparison with nulliparas, the risk of endometrial cancer tended to be lower in

parous women, and the estimated multivariate OR were 0.9, 0.8 and 0.7, respectively,
for women reporting 1, 2 and 3 or more births.2
A major risk factor was the absence of a prior pregnancy (RR 2.8, 95% CI 1.7-4.6). The
protective effect of pregnancy appeared to reflect the influence of term births, because
spontaneous and induced abortions were unrelated to risk. A marked decrease in risk
was associated with a greater number of full term pregnancies. After adjustment for
other reproductive characteristics, age at first birth and duration of breastfeeding were
not related to risk.3
Nulliparity is an independent risk factor for endometrial hyperplasia and carcinoma with
an OR of 2.8 (95% CI 1.1-7.2).4
References:
1. Parazzini F, La Vecchia C, Negri E, et al. Reproductive factors and risk of endometrial

cancer. Am J Obstet Gynecol 1991;164: 522-527.
2. Parazzini F, Negri E, La Vecchia C, et al. Role of reproductive factors on the risk of
endometrial cancer. Int J Cancer 1998;76:784-786.
3. Brinton LA, Berman ML, Mortel R, et al. Reproductive, menstrual, and medical risk
factors for endometrial cancer: results from a case-control study. Am J Obstet Gynecol
1992;167:1317- 1325.
4. Farquhar CM, Lethaby A, Sowter M, et al. An evaluation of risk factors for endometrial
hyperplasia in premenopausal women with abnormal menstrual bleeding. Am J Obstet
Gynecol 1999;181: 525-529.
Statement 5: Diabetes is an independent risk factor for endometrial cancer and

confers about a 2-fold relative risk after adjusting for obesity. (Level II-2, Grade B)
After adjustment for weight and other factors, the effect of diabetes on the development
of endometrial cancer persisted (RR 2.0, 95% CI 1.1-3.6).1
Diabetes was associated with an almost 2-fold increase in risk of endometrial cancer
(OR 1.86, 95% CI 1.37-2.52). Duration of diabetes (compared with no diabetes) was
associated with an increased risk of endometrial cancer (p trend = 0.001).2
Control of diabetes could play a role in the primary prevention of endometrial cancer.
However, there are no outcome studies or recommendations from major medical
organizations about the effectiveness of this approach.3
References:
1992;167:1317- 1325.
2. Shoff SM, Newcomb PA. Diabetes, body size, and risk of endometrial cancer. Am J
Epidemiol 1998;148:234-240.
3. Buchanan EM, Weinstein LC, Hillson C. Endometrial cancer. Am Fam Physician 2009;
80(10):1075-80.
Statement 6: Infertility may elevate risk of endometrial cancer. (Level II-2, Grade
B)
Nulliparous infertile women are 8x at risk for endometrial cancer compared to those
without difficulty conceiving.1
History of infertility was independently associated with increased risk of endometrial

hyperplasia or the presence of carcinoma with an OR 3.6; 95% CI 1.3-9.9.2
References:
1992;167:1317- 1325.
2. Farquhar CM, Lethaby A, Sowter M, et al. An evaluation of risk factors for endometrial
hyperplasia in premenopausal women with abnormal menstrual bleeding. Am J Obstet
Gynecol 1999;181: 525-529.
Statement 7: Late menopause (age ! 55 years) increases risk of endometrial

cancer 2-fold. (Level II-2, Grade B)
Women who had natural menopause at the age of 55 years or older had a RR of
disease 1.87 times (95% CI 1.12-3.09) that of women who had undergone menopause
before age 45 years.1
Reference:
1. McPherson CP, Sellers TA, Potter JD, et al. Reproductive factors and risk of endometrial
cancer. The Iowa Women’s Health Study. Am J Epidemiol 1996;143:1195-1202.
Statement 8: There is an inverse association between age at menarche and

endometrial cancer incidence. (Level II-2, Grade B)
Women who started menstruating at age 15 years or older had about one-third the risk
of endometrial cancer compared with those starting at age 10 years or younger.1
Reference:
1. McPherson CP, Sellers TA, Potter JD, et al. Reproductive factors and risk of endometrial
cancer. The Iowa Women’s Health Study. Am J Epidemiol 1996;143:1195-1202.
Statement 9: Polycystic ovarian syndrome (PCOS) may be a risk factor for

endometrial cancer in younger women. (Level II-2, Grade B)
Case reports have suggested that PCOS, which affects approximately 5% of

reproductive aged women, may be a risk factor for endometrial cancer in younger
women. Coulam, et al observed a 3-fold RR of developing endometrial cancer after a
diagnosis of chronic anovulation.1-4
References:
1. Jafari K, Javaheri G, Ruiz G. Endometrial adenocarcinoma and the Stein-Leventhal

syndrome. Obstet Gynecol 1978;51:97-100.
2. Wood GP, Boronow RC. Endometrial adenocarcinoma and the polycystic ovary
syndrome. Am J Obstet Gynecol 1976;124:140-142.
3. Cirns JD, Noble AJ, Bryant ME. Carcinoma of endometrium and polycystic ovaries in a
22-year-old patient. Can Med Assoc J 1967;96:1473-1476.
4. Coulam CB,Annegers JF, Kranz JS. Chronic anovulation syndrome and associated
neoplasia. Obstet Gynecol 1983; 61:403-407.
Statement 10: Women with hereditary nonpolyposis colorectal cancer (HNPCC)

have a 22-50% lifetime risk of developing endometrial cancer and the disease
tends to occur at a younger age. (Level II-2, Grade B)
Cumulative incidence of endometrial cancer in women with HNPCC was 20% by age 70,
compared to 3% in the general population. In this group, during the highest risk years
(age 40 to 60), average annual risk exceeded 1%. 1
In women who are mutation carriers of DNA-mismatched-repair genes, the standardized

incidence ratios were significantly increased for endometrial cancer (62; 95% CI 44-86),
among other cancers. Interestingly, the incidence of endometrial cancer exceeded that
for colorectal cancer in women (54%).2
References:
1. Watson P,Vasen HF, Mecklin JP, Jarvinen H, Lynch HT. The risk of endometrial cancer
in hereditary nonpolyposis colorectal cancer. Am J Med 1994;96:516-520.
2. Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-
repair genes. Int J Cancer 1999;81:214-218.
Statement 1: Oral contraceptive pill (OCP) use reduced the risk of endometrial
cancer. (Level I, Grade A)
The Cancer and Steroid Hormone (CASH) Study which involved 433 cases and 3191
controls, women who had used combination OCPs for at least 1 year had an age-
adjusted OR of endometrial cancer of 0.6 (95% CI 0.3-0.9). The protective effect began
after 1 year of use and lasted up to 15 years after discontinuing the pills, but it was most
evident in nulliparous women.1
The Royal College of General Practitioners Oral Contraceptive (RCGPOC) Study from
the United Kingdom found more than 40% reduction in risk (RR 0.58; 95% CI 0.42-0.79)
of endometrial cancer among OCP users.2
References:
1. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong
life in postmenopausal women. Ann Intern Med 1992;117:1016–1037.
2. Hannaford PC, Selvarai S, Elliott AM, Angus V, Iversen L, Lee AJ. Cancer risk among
oral contraceptive users: a cohort data from the Royal College of General Practitioners’
Oral Contraceptive Study. BMJ 2007;335:651-8.
Statement 2: Raloxifene reduced the risk of developing endometrial cancer. (Level

I, Grade A)
Raloxifene users had a 50% reduction in the odds of developing endometrial cancer
compared with those who had not used a selective estrogen receptor modulator (SERM)
in an adjusted model (OR 0.50; 95% CI 0.29-0.85).1
In the Study of Tamoxifen and Raloxifene (STAR) Trial, the incidence of invasive breast
cancer with Tamoxifen vs. Raloxifene is 4.30 per 1000 and 4.41 per 1000 (RR 1.02; 95%
CI 0.82-1.28). There were 36 cases of uterine cancer with Tamoxifen and 23 with
raloxifene (RR 0.62; 95% CI 0.35-1.08). No differences were found for other invasive
cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events
occurred less often in the raloxifene group (RR 0.70; 95% CI 0.54-0.91). The number of
osteoporotic fractures in the groups was similar. There was no difference in the total
number of deaths (101 vs 96 for Tamoxifen vs Raloxifene) or in causes of death.2
References:
1. DeMichele A, Troxel AB, et al. Impact of raloxifene or tamoxifen use on endometrial

cancer risk: A population-based case-control study. J of Clin Oncol 2008 Sept
1;26(25):4151-9.
2. Vogel VG, Constatino JP, et al. Effects of tamoxifen vs raloxifene on the risk of
developing invasive breast cancer and other disease outcomes: the NSABP study of
Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006 Jun 21;295(23):2727-41.
Statement 1: For low risk patients, there is no routine screening warranted. (Level
II-2, Grade B)
At the time of menopause, women with no risk factors (i.e. low risk) should be informed
about risks and symptoms of endometrial cancer and strongly encouraged to report any
unexpected bleeding or spotting to physicians.1
Reference:
1. Kim YB, Ghosh K, Ainbinder S, Berek JS. Diagnostic and therapeutic advances in
gynecologic oncology: screening for gynecologic cancer. Cancer Treat Res 1998;95:253–
276.
!
!
Statement 2: For moderate risk patients, there is also no routine screening
warranted. (Level II-2, Grade B)
Women who are at moderate risk for endometrial cancer are those with history of any of
the following: unopposed estrogen therapy, late menopause, Tamoxifen therapy,
nulliparity, infertility, chronic anovulation, obesity and diabetes. Asymptomatic moderate
risk women should be informed about the potential benefits, risks and limitations of
testing early for endometrial caner detection to ensure informed decisions about testing.1
Reference:
1. Zanotti KM, Kennedy AW. Screening for gynecologic cancer. Med Clin North Am 1999
Nov; 83(6):1467-87.
!
!
Statement 3: For high risk patients, annual screening for endometrial cancer with
endometrial biopsy should be offered by age 35 for women with or at risk for
HNPCC. (Level III, Grade C)
Women who are at high risk for endometrial cancer are those known to carry HNPCC-
associated mutations, those who have a substantial likelihood of being a mutation carrier
(i.e. a mutation is known to be present in the family) or those whose families carry an
autosomal dominant predisposition to colon cancer. Women in this high-risk group
should be informed about the risks and symptoms of endometrial cancer, and should be
informed about potential benefits, risks, and limitations of testing for early endometrial
cancer detection.1
Reference:
1. Rumowicz C, Saslow D, et al. American Cancer Society guidelines for the early detection
of cancer: update of early detection guidelines for prostate, colorectal and endometrial
cancers. CA Cancer J Clin 2001;51:38-75.
Statement 4: There is no role for routine screening with endometrial biopsy or

transvaginal ultrasound in asymptomatic women on Tamoxifen. (Level I, Grade A)
One hundred eleven (111) breast cancer patients receiving Tamoxifen underwent a total
of 635 endometrial biopsies, with a mean number of endometrial samplings per patient
of 5.8. Median age was 50 years (range, 33 to 75 years). Five hundred forty-four
endometrial biopsy samples (86%) revealed benign endometrium. Eighty-two (12.9%) of
the samples were insufficient for diagnosis. Nine biopsy specimens were abnormal,
however, type of abnormality was not characterized. Fourteen patients (12.6%)
underwent a dilation and curettage (D&C), with or without a hysteroscopy. Only one
patient had complex hyperplasia detected by D&C, which led to a hysterectomy. There
was successful monitoring of the endometrium in the majority of patients, however, the
screening led to an increase in operative procedures in this asymptomatic group of
patients. This study confirmed the futility of routine endometrial screening biopsies in
asymptomatic patients receiving Tamoxifen.1
The study by Gerber, et al addressed the role of transvaginal ultrasound (TV-UTS) in

247 postmenopausal women with breast cancer and compared them with 98 women
with breast cancer who were not eligible for Tamoxifen. The mean age at first
ultrasonographic assessment was approximately 60 years in both groups. Fifty-two
asymptomatic patients with thickened (10 mm) or morphologically suspect endometrium
underwent hysteroscopy and D&C, which resulted in four uterine perforations. The
majority of the patients with abnormal endometrium displayed atrophic changes. Nine
patients had polyps, four patients had hyperplasia, and one patient had an endometrial
cancer. To detect only one asymptomatic cancer, 1,265 TV-UTS were performed. In
contrast to these asymptomatic patients, among patients with vaginal bleeding, only five
(25%) had atrophic changes while five had polyps, four had hyperplasia, and two had
endometrial cancer.2
Endometrial biopsy, with or without TV-UTS, should be reserved only for patients with
abnormal vaginal bleeding or discharge.
References:
1. Barakat RR, Gilewski TA, Almadrones L, et al. Effect of adjuvant tamoxifen on the
endometrium in women with breast cancer: A prospective study using office endometrial
biopsy. J Clin Oncol 2000;18:3459-3463.
2. Gerber B, Krause A, Mu¨ller H, et al. Effects of adjuvant tamoxifen on the endometrium in
postmenopausal women with breast cancer: A prospective long-term study using
transvaginal ultrasound. J Clin Oncol 2000;18:3464-3470.
V. FIGO 2009 SURGICAL STAGING FOR ENDOMETRIAL CANCER
I* Tu mo r con fin ed to the c orpu s u teri

IA No or le sss s tha n h alf m yo me trial in va sio n
IB In va sion eq ual tot o or mor e th an hal f o f th e myo
m yo me triu m
II* Tu mo r in va de s ce rvi cal str o ma, b ut do es n ot ex te nd be yo nd th e
uter us*
us***
III* Loc al and /or regi onal spre ad of the tu mor ***
Local * **
IIIA Tu mo r in va de s th e ser os a of th e cor pu s uteri a nd/or adn ex ae
IIIB Vagin al and /or par a me trial in vol ve me nt
III C Me ta st a se s to pel vi c and /or par a - ao rti c l y mp h n ode s
C1 Po si tive
tiv e pel vic n ode s
C2 Po si tive para - aor tic l y mph no de s wi th or wi tho ut p osi ti ve
pelvi c ly m ph no de s
IV * Tu mo r in va de s blad der an d/or b o wel mu m u co sa , a nd /or di stant
me ta st a se s
IVA Tu mo r in va si on of bla dder a nd /or bo wel muco sa
IVB Di st ant me ta st
staa se s, in cludi ng intra - a bdo minal m eta s ta se s and /or
inguin al l ymp h n ode s
*Either G1, G2, or G3. Architectural grading of endometrial carcinoma:
G1 no more than 5% of the tumor is composed of solid masses
G2 6-50% of the tumor is composed of solid masses
G3 more than 50% of the tumor is composed of solid masses
**Endocervical glandular involvement only should be considered as Stage I and no longer as

Stage II.
***Positive cytology is no longer included in the surgical staging but it still has to be reported
separately without changing the stage.
VI. WHO CLASSIFICATION OF ENDOMETRIAL CARCINOMA1
A. Adenocarcinoma
1. Endometrioid
a. Variant with squamous differentiation*
b. Villoglandular variant
c. Secretory variant
d. Ciliated cell variant
2. Mucinous
3. Serous
4. Clear cell
B. Mixed cell carcinoma
C. Squamous cell carcinoma
D. Transitional carcinoma
E. Small cell carcinoma
F. Undifferentiated carcinoma
G. Carcinosarcoma
*Zaino, et al recommended that the terms “adenoacanthoma” and “adenosquamous

carcinoma” be replaced by “adenocarcinoma with squamous differentiation”. The
biologic behavior of endometrial carcinoma with squamous elements was similar to that
of typical adenocarcinoma. Division of adenocarcinoma with squamous differentiation by
depth of myometrial invasion and by architectural grade of the glandular component
provided useful prognostic information that was superior to that resulting simply from
division into adenoacanthoma and adenosquamous carcinoma.2
References:
1. Ismael S, Ganesan R, Singh N, McCluggage G. Dataset for histological reporting of

endometrial cancer. The Royal College of Pathologists, January 2010. Document G090,
version 3, pp1-21 (www.rcpath.org)
2. Zaino RJ, Kurman R et al. The significance of squamous differentiation in endometrial
carcinoma. Data from a Gynecologic Oncology Group Study. Cancer 1991;
(68(10)::2293-302.
ENDOMETRIAL CANCER
1. Ninety percent of women with endometrial cancer presents with abnormal vaginal
bleeding or abnormal discharge.1
2. Endometrial biopsy is the gold standard to obtain endometrial tissue for histologic
evaluation.1
3. Further evaluation is warranted in the following circumstances: failure to obtain an
adequate specimen, inconsistencies between biopsy and imaging, and/or
persistence of symptoms despite a benign biopsy result.1
4. Using a 4 mm cut-off point for endometrial thickness, TV-UTS has 100% sensitivity
and 60% specificity as a predictor of endometrial cancer in women reporting
postmenopausal bleeding.2
5. Saline infusion sonography (SIS)/ sonohysterography is often used as a second step
in the evaluation of abnormal bleeding, when ultrasonography suggests a focal
lesion, when endometrial biopsy is nondiagnostic, or when abnormal bleeding
persists despite normal initial workup.3
6. Hysteroscopy is highly accurate in diagnosing endometrial cancer in women with
abnormal bleeding.4
7. Once the diagnosis of endometrial cancer is made, the patient should be referred to
a gynecologic oncologist.5
8. Endometrial cancer follows a surgico-pathologic staging in the form of peritoneal fluid
cytology (PFC), extrafascial hysterectomy (EH) with bilateral salpingooophorectomy
(BSO) and retroperitoneal lymph node dissection.5
9. In selected cases, where there is histopathologic evidence of tumor extension into
the cervical stroma, primary PFC, radical hysterectomy (RH), BSO, pelvic and
paraaortic lymphadenectomy may be performed by a gynecologic oncologist.5
10. Adjuvant treatment in the form of radiotherapy alone or chemotherapy followed by
radiotherapy is given depending on the disease stage, histologic type, tumor grade
and presence of lymphovascular invasion (LVSI).5
11. The treatment of endometrial cancer requires a multidisciplinary approach involving a
gynecologic oncologist and a radiation oncologist.5
References:
1. Walker JL, Nunez ER. Endometrial cancer, in Kramer BS, Gohagan JK, Prorok PC (eds):
Cancer Screening: Theory And Practice. New York, Marcel Dekker, Inc.,1999, pp 531-
566.
2. Gull B, Karlsson B, Milsom I, et al. Can ultrasound replace dilation and curettage? A
longitudinal evaluation of postmenopausal bleeding and transvaginal sonographic
measurement of the endometrium as predictors of endometrial cancer. Am J Obstet
Gynecol 2003;188(2):401-8.
3. Moschos E, Ashfaq R, McIntire DD, Liriano B, Twickler DM. Saline infusion sonography
endometrial sampling compared with endometrial biopsy in diagnosing endometrial
pathology. Obstet Gynecol 2009;113(4): 881-887.
4. Clark TJ, Voit D, Gupta JK, Hyde C, Song F, Khan KS. Accuracy of hysteroscopy in the
diagnosis of endometrial cancer and hyperplasia: a systematic quantitative review. JAMA
2002;288(13): 1610-1621.
5. Society of Gynecologic Oncologists of the Philippines 2008 Clinical Practice Guidelines.
August 2008.
VULVAR CANCER
I. INCIDENCE
• Vulvar cancer makes up 3% to 5% of all gynecologic cancers. The National

Cancer Institute identified vulvar cancer as 1 of the 12 cancers rising in
incidence. At the Philippine General Hospital, there were 7 new vulvar
malignancy cases seen in 2009. The most common histology was squamous
cell carcinoma.1
• The increasing incidence of vulvar carcinoma in situ in United States correlates
with the increase in the incidence of human papilloma virus (HPV) infection. The
increase of in situ vulvar carcinoma has occurred predominantly in women
younger than 65 years, with a peak incidence observed in the 40–49-year-old
age group and steadily decreases thereafter.2
• The increase of in situ vulvar carcinoma, in the Surveillance and Epidemiology
End Result (SEER) database, may be secondary to an increased incidence of
screening, detection and reporting both by the patient and the physician.2
• There is relatively little change in the incidence of invasive vulvar cancer,
particularly in women younger than 50 years there is a steady increase in
incidence of invasive vulvar cancer with age. The different age distributions
between invasive vulvar and cervical cancers (in combination with in situ
disease) suggest that other risk factors, aside from HPV, are related to the
development of invasive vulvar cancer.3
References:

General Hospital Annual Statistics 2009.
2. National Cancer Institute. SEER public use data, 1973-2001, 2004
3. Judson P, et al. Trends in the incidence of invasive and in situ vulvar carcinomas. ACOG
2006 May;107:1018-1022.
II. RISK FACTORS
Statement 1: HPV infection increases the risk of developing vulvar cancer. (Level
II-2, Grade B)
The relative risk (RR) of developing vulvar cancer in patients with HPV infection is 15
(95% CI 5.5-42.1). This was elevated even further among subjects reporting multiple
episodes of genital warts (RR 36.3, CI 4.6-286).1
Reference:
1. Brinton LA, Nasca PC, Mallin K, et al. Case-control study of cancer of the vulva. Obstet
Gynecol 1990;75:859-866.
Statement 2: Herpes simplex virus 2 (HSV 2) infection increases the risk of

developing vulvar cancer. (Level II-2, Grade B)
HSV 2 was associated with increased risk of vulvar cancer (Odds Ratio [OR] 1.9, 95%
CI 1.4-2.6) for vulvar cancer in situ, OR 1.5 (95% CI 0.9-2.6) for invasive vulvar cancer). 1
A case-control study with 466 patients seropositive to HSV-2 were at higher risk for
vulvar carcinoma (RR 2.0, 95% CI 0.9-1.3).2
Reference:
1. Madeleine M, et al. Cofactors with human papillomavirus in a population-based study of

vulvar cancer. J Natl Cancer Inst 1997;89(20):1516-23.
2. Sherman KJ, et al. Genital warts, other sexually transmitted diseases, and vulvar cancer.
Epidemiology 1991;2,257-262.
Statement 3: Smoking increases the risk of developing vulvar cancer. (Level II-2,
Grade B)
Current smokers have a higher risk of developing vulvar cancer as compare to former
smokers (RR 2.03; 95% CI 1.3-3.3 vs RR 1.34; 95% CI 0.9-2.0, respectively).1 There is
increased risk for vulvar cancer among women who are both current smokers and HPV
16 seropositive, with the association being strongest for women with in situ disease (OR
6.4 (95% CI 4.4-9.3) for in-situ and OR 3.0 (95% CI 1.7-5.3) for invasive cancer).2
HPV (with smoking as a cofactor) is thought to lead to transformation and expression of

a malignant phenotype, in a multistage process, that interferes with the ability of the host
genome to impede oncogenesis in proliferating cells. The combination of cigarette
smoking and HPV could be particularly important in abrogating control on two
components of cell kinetics: proliferation and programmed cell death.3
References:
Gynecol 1990;75:859-866.
2. Madeleine M, et al. Cofactors with human papillomavirus in a population-based study of
vulvar cancer. J Natl Cancer Inst 1997;89(20):1516-23.
3. Yang X, et al. A malignant transformation of HPV 16 – immortalized human endocervical
cells by cigarette smoke condensate and characterization of multistage carcinogenesis,
Int J Cancer 1996:65;338-344.
Statement 1: Sexual total abstinence and practice of lifetime mutual monogamy.

The risk of vulvar cancer was related to the number of lifetime partners. Although this
was not an entirely dose-response relationship, women who reported 5 or more partners
had 2- to 3-fold excess risks compared with subjects who reported 1 or no partners.1
Reference:
Gynecol 1990;75:859-866.
Statement 2: Prophylactic HPV vaccination can protect women from developing

vulvar intraepithelial neoplasia (VIN). (Level I, Grade A)
HPV is associated with approximately half of vulvar squamous cell cancers, the most
common type of vulvar cancer. HPV-associated vulvar cancer tends to occur in younger
women (46 years old and below) and might be preceded by VIN. In a recent study, HPV
types 16 or 18 were detected in 76% of the VIN 2/3 and 42% of vulvar carcinoma
samples.1
A randomized, placebo-controlled, double-blind phase III trial (FUTURE 1) involving

quadrivalent HPV vaccine and 5,455 women between the ages 16-24 years old
investigated the occurrence of VIN and vulvar cancer associated with HPV 6, 11, 16, 18.
The vaccine efficacy was 100% for the vulvar diseases (external anogenital and vaginal
lesions). An intention-to-treat analysis (regardless of the baseline HPV status) showed
an efficacy of 73% (95% CI 58-83) when all grades of external anogenital or vaginal
lesions were combined (28 cases in the vaccine group vs. 102 cases in the placebo
group) and 55% (95% CI 40 to 66) when all grades of cervical lesions were combined.2
References:
1. Hampl M, et al. Effect of human papillomavirus vaccines on vulvar, vaginal, and anal
intraepithelial lesions and vulvar cancer. ACOG 2006 Dec;108(6):1361-1368.
2. Garland S, et al. Quadrivalent vaccine against human papillomavirus to prevent
anogenital diseases. N Engl J Med 2007 May 10;356:1928-1943.
Statement 3: There should be prompt and appropriate diagnosis and treatment of

VIN. (Level III, GPP)
Clinical evidence shows that in 3-17% of patients with VIN 3 progress to invasive
squamous cancer of the vulva. In the absence of definitive information about the natural
history of VIN and its risk of progression, treatment should be undertaken not only to
control the symptoms, but also to prevent a potential malignant transformation.1
Reference:
1. Bosze P. European Academy of Gynecologic Cancer. Course on Colposcopy, Chapter

14, page 152.
Statement 4: Prompt diagnosis and treatment of lichenoid pattern vulvar

dermatotes may decrease the likelihood of type II vulvar cancer development.
(Level III, GPP)
The first etiologic type of vulvar cancer is seen mainly in younger patients, that is related
to HPV infection and smoking, and is commonly associated with basaloid or warty VIN.
The second etiologic type which is seen mainly in elderly patients is more common. It is
unrelated to smoking or HPV infection, and concurrent VIN. There is a high incidence of
lichenoid lesions, including lichen sclerosus, adjacent to the tumor.1
Reference:
1. Scurry J, Campion M, Scurry B, Kim SN, Hacker NF. Pathologic audit of 164 consecutive
cases of vulvar intraepithelial neoplasia. Int J Gynecol Path 2006;25:176-181.
Statement 5: Routine gynecologic examination should include thorough

inspection of the external genitalia. (Level III, GPP)
The physician may be the cause of delay in diagnosis due to insufficient knowledge of
vulvar diseases. Examination of the vulva is haphazardly done - or not done at all -
resulting in empirical therapy without the benefit of biopsy for a definitive diagnosis.
Such delays in diagnosis result in the high percentage of advanced lesions. This is
unfortunate because the vulva is very accessible and examination does not require
sophisticated equipment. A good light and simple magnifier are usually sufficient.1
Reference:
1. Sotto L, Manalo A, Limson G. Gynecologic Oncology for the Clinician. SGOP, 1994.
Statement 1: There is no routine screening recommended for vulvar cancer. (Level

III, GPP)
The ability of screening tests to detect preinvasive or invasive disease is highly

dependent on the individual characteristics of the cancer being screened. The
prevalence of the disease is perhaps the largest predictor of a given screening test’s
positive predictive value, making low cancers with low incidence practically impossible to
screen. Given the extremely low prevalence of squamous cell carcinoma of the vulva, in
addition to the incomplete association with HPV, it seems unlikely that any population
screening test will be feasible or effective.1
References:
1. Benedet J, et al. Staging classifications and clinical practice guidelines for gynecological
cancers: A collaboration between FIGO and IGCS. Int J Gynecol Oncol 2006;70:217-312.
2. Growdon W, Del Carmen M. Human papillomavirus–related gynecologic neoplasms:
Screening and prevention. Rev Obstet Gynecol 2008;4:154-161.
V. FIGO 2009 SURGICAL STAGING FOR VULVAR CANCER
I Tu mo r con fin ed to the vulva
vulv a or perin eu m,
m , No no dal meta sta si s
IA Lesi on s " 2 cm in size wi th s tro mal in v asi on < 1 m
mmm
IB Lesi on s > 2 c m in si ze or with stro mal in vasio n > 1 m m
II Tu mo r of an y si ze wi th e xte nsi on to adjac ent lo wer perin eal
str uctur
uc tur es (1 /3 lo we r ure thr a, 1/3 lo wer vagina , a nu s) with ne ga tiv e
node s
III T u mo r o f an y si ze wit
withh o r wi tho ut e xten sio n to adja ce nt peri neal
str uctur
uc tur es (1 /3 lo wer ur ethra , 1 /3 lo we r va gina , a nu s) wi th po si tiv e
inguin o - f e moral l ymph no de s
IIIA Wi th 1 l ymp y mp h n ode me ta stasi s ( ! 5 mm) or 1 - 2 lym ph nod e
me ta st a sis( es) ( < 5 mm)
sta m m)
IIIB Wi t h ! 2 l ymp h n ode metasta metas ta se s ( ! 5 mm) or ! 3 l ym ph node
y mph
me ta st a se s ( < 5 m
sta m)
mm)
III C Wi th po siti v e n ode s with e x tra cap sul ar spr ead
IV Tu mo r in va de s o th er re gion al (2 /3 up per urethra , 2 /3 upp er va gina)
or di stan t sstru
tru ct ure s
IVA Tu mo r in vad es an y o f the follo w in g: upp er ure thral and /or va ginal
mu co sa , bla dder mu co sa , rec tal mu co sa or fixe d to pel vi c bon e or
fix ed or ul cera ted in guin o - fe moral no de s
fixed
IVB Any di stan t m et asta
met as ta se s,
s , in clu ding p elvi c ly mp h n ode s
lymp
VI. WHO HISTOLOGICAL CLASSIFICATION OF VULVAR TUMORS
A. Epithelial neoplasms of skin and mucosa

1. Invasive Squamous cell carcinoma
a. Keratinizing
b. Non-keratinizing
c. Basaloid carcinoma(1)*
(i) Verrucous
(ii) Warty carcinoma [condylomatous](1)*
2. Basal cell carcinoma
3. Adenocarcinoma
B. Bartholin gland carcinomas
2. Adenocarcinoma
4. Adenosquamous carcinoma
5. Transitional cell carcinoma
6. Undifferentiated
C. Carcinoma and sarcoma of ectopic breast tissue
D. Carcinoma of sweat gland origin
E. Soft tissue sarcomas
1. Embryonal rhabdomyosarcoma (sarcoma botryoides)
2. Leiomyosarcoma
3. Malignant fibrous histiocytoma
4. Epithelioid sarcoma
5. Aggressive angiomyxoma
6. Dermatofibrosarcoma protuberans
7. Epithelioid sarcoma
8. Malignant rhabdoid tumor
9. Malignant nerve sheath tumor
10. Angiosarcoma
11. Kaposi sarcoma
12. Hemangiopericytoma
13. Liposarcoma
14. Alveolar soft part sarcoma
15. Other sarcomas (Enzinger & Weiss or WHO)
F. Other malignant tumors
1. Malignant melanoma
2. Endodermal sinus tumor (yolk sac tumor)
3. Neuroectodermal tumors (Merkel cell)
4. Lymphomas
5. Others
G. Secondary and metastatic tumors
H. Unclassified tumors
VII. GENERAL GUIDELINES IN THE DIAGNOSIS AND MANAGEMENT OF VULVAR

CANCER
1. Any suspicious vulvar discoloration, ulceration and lesion should be biopsied.1,2

2. Expert opinion recommends that any lesion increasing in size or with an unusual
warty appearance should be biopsied. Any typical condyloma that does not respond
to therapy should be biopsied. The clinician must be diligent in observing any vulvar
lesions and use biopsy aggressively on any lesion of concern to the clinician or
patient.
3. The biopsy should include surrounding skin with underlying dermis and connective
tissue so that the pathologist can evaluate the depth of stromal invasion.
4. Vulvar cancer is clinically staged.2
5. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done to rule
out bladder and bowel involvement.
6. Imaging studies like computer tomography (CT) scan and magnetic resonance
imaging (MRI) of the pelvic and groins is often helpful in detectling enlarged lymph
nodes in the groins and pelvis.3
7. Sentinel lymph node biopsy provides an accurate and safe alternative to
conventional groin node dissection with significantly less morbidity.
References:
th
1. Moore D, et al. Principle and Practice of Gynecologic Oncology, 5 edition, chapter 20,
2009.
2. Canavan T, Cohen D. Vulvar cancer. AFP 2001 October 1;66(7):1269-1274.
3. Javitt MC, Reuter K, Troiano R. Current status on imaging carcinoma of the vulva. J
Women’s Imaging 2002;4(3):122-125
4. Van der Zee AG, et al. Sentinel node dissection is safe in the treatment of early-stage
vulvar cancer. J Clin Oncol 2008;26(6): 884-
SGOP Clinical Practice Guidelines for the Obstetrician Gynecologist 2010
August 2010
VAGINAL CANCER
I. INCIDENCE
• Vaginal cancer is a rare malignancy accounting for about 0.3% of all invasive
cancers among women and for 1% to 2% of all gynecologic malignancies in the
United States annually.1
• In 2009, there were 4 new cases of vaginal cancer seen in Philippine General
Hospital.2
References:
1. Xiaocheng W, et al. Descriptive epidemiology of vaginal cancer incidence and survival by

race, ethnicity and age in the United States. American Cancer Society, November 2008.
General Hospital Annual Statistics 2009.
II. RISK FACTORS
Statement 1: Human papilloma virus (HPV) infection increases the risk of vaginal
Vaginal cancer have many of the same risk factors as cervical cancer, including a strong
relationship to HPV infection. A population-based case-control study was done to evaluate
risk factors for vaginal cancer and their potential relationship to prior exposure to HPV. Blood
samples were tested for antibodies to HPV. Antibodies to HPV 16 L1 were strongly related
to risk of vaginal cancer (Odds Ratio [OR] 4.3, 95% CI 3.0-6.2). HPV DNA was in tumor
blocks from over 80% of the patients with in situ and 60% of the patients with invasive
cancers.1
The connection between vaginal dysplasia and vagional squamous cell carcinoma is not well
established, but investigations have observed that oncogenic HPV affects 90% to 100%of
VAIN and 60% to 70% of vaginal squamous cell carcinoma.2
References:
1. Daling JR, Madeleine MM, Schwartz SM, et al. A population-based study of squamous cell
vaginal cancer: HPV and cofactors. Gynecol Oncol 2002;84:263–270.
2. Insinga RP, Liaw KL, Johnson LG, Madeleine MM. A systematic review of the prevalence and
attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and
cancers in the United States. Cancer Epidemiol Biomarkers Prev 2008;17:1611-1622.
Statement 2: A five or more lifetime sexual partner increases the risk of developing
vaginal cancer. (Level II-2, Grade B)
In the same study, women with vaginal cancer were more likely to have five or more lifetime
sexual partners (OR 3.1, 95% CI 1.9 -4.9).1
58
August 2010
Reference:
vaginal cancer: HPV and cofactors. Gynecol Oncol 2002;84:263–270
Statement 3: A history of cervical cancer increases the risk of developing vaginal

Approximately 30% of all vaginal cancer cases in the population-based control study had
been treated for a prior anogenital tumor, most often of the cervix.1
Patients with previous cervical cancer have a substantial risk of developing vaginal cancer,
because these sites share exposure and susceptibility to endogenous or exogenous
carcinogenic stimuli. 10-50% of patients with VAIN–carcinoma in situ (CIS) or invasive
carcinoma of the vagina have undergone prior hysterectomy or radiotherapy for CIS or
invasive carcinoma of the cervix.2
The interval from treatment for cervical cancer or preinvasive disease to the development of
carcinoma of the vagina averages nearly 14 years, but there have been cases with the
vaginal primary manifesting 50 years after therapy for cervical cancer.3
References:
vaginal cancer: HPV and cofactors. Gynecol Oncol 2002;84:263–270.
2. Andersen ES. Primary carcinoma of the vagina: a study of 29 cases. Gynecol Oncol
1989;33:317–320.
3. Gallup DG, Talledo OE, Shah KJ, et al. Invasive squamous cell carcinoma of the vagina. A
14-year study. Obstet Gynecol 1987;69:782–785.
Statement 4: In–utero diethylstilbestrol (DES) exposure increases the risk of

developing vaginal cancer. (Level II-3, Grade C)
In a retrospective study of women diagnosed with clear cell carcinoma done by Hanselaar,
et al, 41% of patients diagnosed with vaginal clear cell carcinoma were exposed to DES in
utero.1
Reference:
1. Hanselaar A, et al. Clear cell adenocarcinoma of the vagina and cervix, an update of the
central Netherlands registry showing twin age incidence peaks. Cancer 1997;79(11):2229-36.
Statement 1: Sexual total abstinence and practice of lifetime mutual monogamy.

59
August 2010
In a population-based study of 36,856 women, alcoholic women had an excess risk for
cancer of the vagina, probably related to higher incidence of HPV infection associated with
lifestyle factors such as promiscuity.1
Reference:
1. Weiderpass E, Ye W, Tamimi R, et al. Alcoholism and risk for cancer for the cervix uteri,
vagina, and vulva. Cancer Epidemiol Biomarkers Prev 2001;10(8):899-901.
Statement 2: Use of barrier methods decrease the risk of HPV infection, thus
decreasing the risk of developing vaginal cancer. (Level II-2, Grade B)
Winer, et al. reported that the rate of incident HPV infections was 25.3 per 100 years at risk
among sexually active women with no new partners and increased to 114.5 and 224.4 per
100 years at risk among those with one and more than one new partners, respectively.
Consistent condom use reduced the rate of incident infections by more than half.1
Reference:
1. Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human
papillomavirus infection in young women. N Engl J Med 2006;354:2645.
Statement 3: HPV vaccination can protect women from developing VAIN. (Level I,
Grade A)
The randomized, placebo-controlled, double-blind phase III trial (FUTURE I) included the
incidence of VAIN lesion as one of its coprimary composite end points. The efficacy of the
vaccine against VAIN is 100%.1
Reference:
1. Garland S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital

diseases. N Engl J Med 2007 May 10;356:1928-1943.
Statement 1: There is no routine screening recommended for vaginal cancer. (Level II-
2, Grade B)
Vaginal cancer as a primary is very rare and usually occurs from a metastasis from another
primary (cervical, vulvar, endometrial). In a descriptive study of the incidence of vaginal
cancer in the United States done from 1998-2003 using 39 population-based cancer
registries, the incidence rate of invasive vaginal cancer is 0.69 per 100,000 female
population and 0.18 per 100,000 female population for the in-situ.1
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August 2010
Reference:
th
1. Brian M. Slomovitz, Chapter 9, Clinical Gynaecologic Oncology, 7 Edition, 2007.
Statement 2: For patients who underwent total hysterectomy for benign gynecologic
disease, vaginal smear is not recommended. (Level II-2, Grade A)
A study by Pearce, et al reviewed 9,610 vaginal smears from women who underwent
hysterectomy for benign gynecologic disease. The prevalence of abnormal findings on
vaginal smears after hysterectomy for benign gynecologic disease is very low (1.1%).1
However, vaginal smear should be continued after hysterectomy for those who have any of
the following risk factors: history of multiple sexual partners, early initiation of intercourse,
sexual partners who had other partners with cervical cancer, current or prior HPV or
condyloma, herpes simplex virus, HIV, history of sexually transmitted diseases,
immunosuppressed state, substance abusers, low socioeconomic status and/or history of in-
utero DES exposure.2
References:
1. Pearce K, et al. Cytopathological findings on vaginal papanicolaou smears after hysterectomy

for benign gynecologic disease. Massacheusetts Medical Society, 1996
2. Fetters M, et al. Effectiveness of vaginal papanicolaou smear screening after total
hysterectomy for benign disease. JAMA 1996;275.
Statement 3: Patients who underwent total hysterectomy for cervical dysplasia or

cancer and those who had history of previous genital dysplasia or cancer should
undergo routine annual vaginal smear (for the next 20 years). (Level II-3, Grade B)
In a retrospective review involving 998 patients with multicentric dysplasias (cervical

intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), VAIN) from 1996 to
2003, 91% had cervicovaginal or cervicovulvar lesions, only 9% had three sites of genital
dysplasia. Approximately fifty-three percent (53.3%) of lesions were concomitant. 79.5% of
CIN were high grade, 62.5% of VAIN low grade and 62.5% of VIN high grade.1
Reference:
1. Menguellet, et al. Management of multricentric lesions of the lower genital tract, Eur J Obstet
Gynecol Reprod Bio 2007;132:116-120.
V. FIGO 2009 SURGICAL STAGING FOR VAGINAL CANCER
I The car cin o ma i s li mited

mit ed to the wall.
II The car cin o ma h as in vol v ed the sub s ub va ginal ti ssue but ha s no t
exten ded to
to the p elvi c wall.
III The car cin o ma ha s exte nded to th e pel vic wall .
IV The car cin o ma ha s e xte nde d be yon d th e true p elvi s or ha s in vol ved
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August 2010
the mu co sa o f t he bla dder or r ec tu m m;; bu llous e de ma a s su ch d oe s

not per mi t a c ase
as e to be allo tted to S ta ge IV.
IVA Sprea d o f th e gr o wth tto
o the adj ac en t or g ans an d/or dir ec t ex te nsi on
beyond tthe
he tr ue pel vi s
IVB Sprea d to di st an t or gan s
VI. WHO HISTOLOGICAL CLASSIFICATION OF VAGINAL TUMORS
I. Epithelial Tumors
A. Squamous cell carcinoma
1. Keratinizing
2. Nonkeratinizing
3. Verrucous
4. Warty (condylomatous)
B. Adenocarcinoma
1. Clear cell
2. Endocervical type
3. Endometrioid type
4. Intestinal type
5. Mesonephric
C. Other invasive tumors
1. Adenosquamous carcinoma
3. Carcinoid tumor
4. Small cell carcinoma
5. Undifferentiated carcinoma
II. Mesenchymal tumors

A. Leiomyosarcoma
B. Sarcoma botryoides (embryonal rhabdomyosarcoma)
C. Endometrioid stromal sarcoma
D. Other
III. Mixed epithelial and mesenchymal tumors

A. Mixed tumor
B. Adenosarcoma
C. Malignant mesodermal mixed tumor
D. Tumor resembling synovial sarcoma
IV. Other
A. Malignant melanoma
B. Yolk sac tumor (endodermal sinus tumor)
C. Lymphoma/leukemia
V. Metastatic tumor
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August 2010
VII. GENERAL GUIDELINES IN THE DIAGNOSIS AND MANAGEMENT OF VAGINAL

CANCER
1. A thorough physical examination with detailed speculum inspection, digital palpation,

colposcopic and cytologic evaluation, and biopsy should be done in order to diagnose
and clinically stage vulvar cancer 1.
2. Biopsy of the cervix, if present is recommended to rule out a primary cervical tumor1.
3. Complete systematic evaluation for patients with malignanct melanoma and advanced
stage vaginal cancer should be performed.
4. Radiation therapy is the treatment of choice for most patients with vaginal cancer, and
comprises of integration of teletherapy and intracavitary/interstitial therapy.
References:
1. Barakat R, et al. Principles and Practice of Gynecologic Oncology, 5th Edition, 2009
2. National Cancer Institute. National Institute of Health. www.cancer.gov
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August 2010
BREAST CANCER
I. INCIDENCE
• Breast cancer is the 2nd leading site for both sexes combined (13.1%) and ranks 1st
among women (25.6%). In 2005, an estimated 14,043 new cases were seen among
women, and 6,357 deaths were expected. In the Philippines, the median survival
among females is 60 months. Survival at the 5th year is 50.10%, and 32.38% at the
10th year. Incidence starts rising steeply at age 30.1
Reference:
1. Laudico AV, Esteban DB, Redaniel MT, Mapua CA, and Reyes LM. 2005 Philippine Cancer
Facts and Estimates, Philippine Cancer Society, Inc., 2004.
II. RISK FACTORS
Statement 1: Increased exposure to estrogen increases the risk of postmenopausal

breast cancer. (Level II-2, Grade B)
Supporting Table:1
!
Lifetime Reproductive and Effect on Risk of Postmenopausal
Anthropometric Risk Factors for Breast Cancer
Breast Cancer in Postmenopausal Increases Risk Decreases Risk
Women of Breast Cancer of Breast Cancer
Pregnancy Status
Preeclampsia +
Twins +
Increased birth weight +
Having been breast fed No effect
Childhood obesity +
Adult height +
Obesity +
Young age at menarche +
Parity
Age at first live birth > 30 years old +
Nulliparity +
Multiple births No effect
Abortion No effect
Lactation +/-
Oophorectomy (esp < 40 years old) +
Age at menopause (risk ~ 3% for +
each additional year)
Reference:
1. Vogel VG. Epidemiology, genetics, and risk evaluation of postmenopausal women at risk of
breast cancer. Menopause 2008;15(4): 782-789.
Statement 2: Increased alcohol consumption increases the risk of breast cancer.

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August 2010
The only well established individual diet-related risk factor for breast cancer other than
obesity is alcohol consumption. Moderate alcohol intake increases breast cancer risk by
approximately 7% per alcoholic drink per day, perhaps by increasing estrogen levels, and
moderate alcohol consumption had been thought to be mitigated by adequate folate intake.1
Reference:
Statement 3: Higher red meat intake in adolescence may increase the risk of
premenopausal breast cancer. (Level II-2, Grade B)
The Nurse’s Health Study II showed that compared with women in the lowest quintile of red
meat intake during high school, the multivariate-adjusted relative risk (RR) for the highest
quintile of intake was 1.34 (95% CI 0.94-1.89; p trend = 0.05). A significant linear association
was observed with every additional 100 g of red meat consumed per day (RR 1.20; 95% CI
1.00-1.43; p = 0.05). This association was more pronounced in hormone receptor-positive
tumors (RR 1.36; 95% CI 1.08-1.70; p = 0.008) and was not significant in hormone receptor-
negative tumors (RR 0.99; 95% CI 0.61-1.61, p = 0.97).1
Reference:
1. Linos E, et al. Red meat consumption during adolescence among premenopausal women
and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2008;17(8):2146–51.
Statement 4: High-fat diets, phytoestrogen consumption, high intake of diary

products, high concentrations of polychlorinated biphenyls (PCBs) and green tea
consumption show inconclusive evidence regarding risk of breast cancer. (Level I,
Grade A)
Populations with high fat intakes generally have higher rates of breast cancer, but studies of
individual women have not confirmed an association of high-fat diets with breast cancer risk.
Phytoestrogens can affect hormone metabolism, but data on phytoestrogen consumption
and breast cancer risk are inconsistent. Several cohort and case-control studies have
investigated the relationship between dairy product intake and breast cancer risk. Most of
these studies showed no consistent pattern of increased or decreased breast cancer risk
with a high consumption of dairy products as a whole or when broken down into high-fat and
low-fat dairy products, milk, cheese or butter. Some PCBs have shown estrogenic effects,
and this has raised concern that they may increase the risk of breast cancer. However, the
majority of prospective and retrospective studies do not show any association between total
PCB concentrations and breast cancer risk. The epidemiologic evidence does not support
an association of environmental exposure to PCBs in adulthood in the general population
and risk of breast cancer, although uncertainties remain for selected subgroups of women or
individual PCB congeners.1
Fifty-one studies with more than 1.6 million participants, mainly of observational nature were
included in this systematic review. Studies looked for an association between green tea
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August 2010
consumption and cancer of the digestive tract, gynecological cancer including breast cancer,
urological cancer including prostate cancer, lung cancer and cancer of the oral cavity. The
majority of included studies were of medium to high methodological quality. The evidence
that the consumption of green tea might reduce the risk of cancer was conflicting. This
means, that drinking green tea remains unproven in cancer prevention, but appears to be
safe at moderate, regular and habitual use.2
References:
2. Boehm K, Borrelli F, Ernst E, Habacher G, Hung SK, Milazzo S, Horneber M. Green tea
(Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Revs 2009, Issue
3. Art. No.: CD005004. DOI: 10.1002/14651858.CD005004.pub2.
Statement 5: The use of combined conjugated equine estrogen (CEE) and

medroxyprogesterone acetate (MPA) as hormone replacement therapy (HRT) for
women age 63.2 (± 7.1) increases the risk of breast cancer. (Level I, Grade A)
Women’s Health Initiative (WHI) analysis shows that using combined CEE and MPA HRT at
age 63.2 (± 7.1) increased breast cancer risk by 23%. Using an intent-to-treat analysis,
estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR] 1.24; weighted
p < .001) and invasive (199 vs. 150 cases; HR 1.24; weighted p =.003) breast cancers
compared with placebo. The invasive breast cancers diagnosed in the estrogen plus
progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1]
vs. 1.5 [0.9], respectively; p =.04) and were at more advanced stage (regional/metastatic
25.4% vs. 16.0%, respectively; p =.04) compared with those diagnosed in the placebo
group. After 1 year, the percentage of women with abnormal mammograms was
substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared
with placebo group 9398 [5.4%] of 7310; p <.001), a pattern which continued for the study
duration.1
Reference:
1. Chlebowski RT, et al. Influence of estrogen plus progestin on breast cancer and
mammography in healthy postmenopausal women – The Women’s Health Initiative
randomized trial. JAMA 2003; 289:3243-3253.
Statement 6: The use of conjugated equine estrogens (CEE) replacement therapy in

women age 63.6 (± 7.3) years does not increase the risk of breast cancer. (Level I,
Grade A)
WHI analysis showed that after a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast
cancer HR for women age 63.6 (± 7.3) years assigned to CEE vs placebo was 0.80 (95% CI
0.62-1.04; p = 0.09) with annualized rates of 0.28% (104 cases in the CEE group) and
0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR
0.71; 95% CI 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test
for interaction by tumor type was not significant (p = 0.054). At 1 year, 9.2% of women in the
CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo
group (p = 0.001), a pattern that continued through the trial to reach a cumulative
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August 2010
percentage of 36.2% vs 28.1%, respectively (p = 0.001); however, this difference was

primarily in assessments requiring short interval follow-up.1
Reference:
1. Marcia L, et al. Effects of Conjugated Equine Estrogens on Breast Cancer and

Mammography Screening in Postmenopausal Women With Hysterectomy. JAMA. 2006;
295(14): 1647-1657.
Statement 7: The use of oral contraceptive pills (OCP) does not increase the risk of
breast cancer. (Level II-2, Grade B)
Royal College of General Practitioners Oral Contraception (RCGPOC) Study did not show
that using OCP increases the risk of breast cancer (adjusted RR 0.98, 95% CI 0.87-1.10).1
Reference:
1. Hannaford PC, et al. Cancer risk among users of oral contraceptives: cohort data from the
Royal College of General Practitioner’s oral contraception study. BMJ 2007.
Statement 8: Mutations in the BRCA 1/2 genes (Hereditary Breast-Ovarian Cancer

Syndrome) increase the risk of breast cancer. (Level II-2, Grade B)
BRCA 1 and 2 gene mutations increase the risk for breast cancer by 60-85% and 26-85%,
respectively.1
Reference:
1. Barakat & Rubin, Contemporary OB/GYN, Feb 2002.
Statement 9: Benign breast lesions which show atypical proliferation increase breast
cancer risk. (Level II-2, Grade B)
Supporting Table:1
Risk Proliferation Histologic findings

No increase Minimal Fibrocystic changes (within the
normal range): cysts and ductal
ectasia (72%), mild hyperplasia
(40%), nonsclerosing adenosis
(22%), and periductal fibrosis
(16%); simple fibroadenoma
(15-23%); and miscellaneous
(lobular hyperplasia, juvenile
hypertrophy, and stromal
hyperplasia)
Benign tumors: hamartoma, lipoma,
phyllodes tumor, solitary
papilloma, neurofibroma, giant
adenoma, and
adenomyoepithelioma
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August 2010
Traumatic lesions: hematoma, fat

necrosis, and lesions caused by
penetration by a foreign body
Infections: granuloma and mastitis
Sarcoidosis
Metaplasia: squamous and apocrine
Diabetic mastopathy
Small increase Proliferative Usual ductal hyperplasia, complex
(RR = 1.5 – 2.0) without atypia fibroadenoma (containing cysts
93 mm in diameter, sclerosing
adenosis, epithelial calcifications,
or papillary apocrine changes),
papilloma or papillomatosis, radial
scar, and blunt duct adenosis
Moderate increase Proliferative with Atypical ductal hyperplasia and
(RR > 2.0) atypia atypical lobular hyperplasia
Reference:
Statement 11: The radiation of mammography does not increase the risk of breast
In mammography radiation of 0.1 rad (2-view), the risk in breast cancer development is
negligible compared with benefits of discovery of early and potentially curable breast cancer.
For women age 50-75 years, the benefit outweighs the risk by 100-fold while for women age
35-75 years, the benefit outweighs the risk by 25-fold.1
Reference:
1. American Cancer Society, 2003.
Statement 1: Weight loss after menopause reduces risk of postmenopausal breast

Excess weight and weight gain in adult life are related to higher risk of postmenopausal
breast cancer, and newer data support the contention that weight loss after menopause is
associated with substantially reduced risk. In addition, physical activity and the prevention of
weight gain can improve survival after a breast cancer diagnosis, and convincing
epidemiologic evidence exists that physical activity reduces breast cancer risk. The
association may differ by menopausal status because stronger evidence of a risk reduction
exists for postmenopausal than for premenopausal women.1
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August 2010
Reference:
Statement 2: Folic acid supplementation does not reduce risk of breast cancer. (Level
II-2, Grade B)
Epidemiologic studies generally suggest an inverse association between dietary intake and
blood measurements of folate and breast cancer risk. However, the Prostate, Lung,
Colorectal, and Ovarian Cancer Screening trial reported a potential harmful effect of high
folate intake on breast cancer risk. In this study, the risk of developing breast cancer was
significantly increased by 20% in women reporting supplemental folic acid intake of 400 kg/d
or more compared with those reporting no supplemental intake. Furthermore, although food
folate intake was not significantly related to breast cancer risk, total folate intake, mainly
from folic acid supplementation, significantly increased breast cancer risk by 32%. These
data support previous observations made in epidemiologic, clinical, and animal studies
suggesting that folate exerts dual effects on the development and progression of cancer
depending on the timing and dose of folate intervention. Based on the current lack of
compelling supportive evidence, routine folic acid supplementation should not be
recommended as a preventive measure against breast cancer.1
Reference:
breast cancer. Menopause 2008;15(4):782-789.
Statement 3: Nonsteroidal anti-inflammatory drugs (NSAID) use reduces the risk for
breast cancer. (Level I, Grade A)
A meta-analysis of 38 studies (16 case-control studies, 18 cohort studies, 3 case-control

studies nested in well-defined cohorts, and 1 clinical trial) that included 2,788,715 subjects
were identified. The results of these studies suggest that overall, NSAID use was associated
with reduced risk for breast cancer (RR 0.88, 95% CI 0.84-0.93). Specific analyses for
aspirin (RR 0.87, 95% CI 0.82-0.92) and ibuprofen (RR 0.79, 95% CI 0.64-0.97) yielded
similar results.1
Reference:
1. Takkouche B, et al. Breast cancer and use of nonsteroidal anti-inflammatory drugs: A Meta-
analysis. J Natl Cancer Inst 2008;100(20):1439-1447.
Statement 4: The use of selective estrogen receptor modulators (SERMs) decreases

the risk of breast cancer development. (Level I, Grade A)
The National Surgical Adjuvant Breast and Bowel Project (NSABP) study results after 7
years of follow-up showed that the cumulative rate of invasive breast cancer was reduced
from 42.5 per 1000 women in the placebo group vs 24.8 per 1000 women in the tamoxifen
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August 2010
group (RR 0.57, 95% CI 0.46-0.70). Also, the cumulative rate of noninvasive breast cancer
reduced from 15.8 per 1000 women in the placebo group vs 10.2 per 1000 women in the
tamoxifen group (RR 0.63, 95% CI 0.45-0.89).1
The Study of Tamoxifen and Raloxifene (STAR) trial revealed that raloxifene was as
effective as tamoxifen in reducing the risk of invasive breast cancer. There were 163 cases
of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to
raloxifene (incidence, 4.30 per 1000 vs 4.41 per 1000; RR 1.02; 95% CI 0.82-1.28). There
were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the
raloxifene group (80 cases) (incidence, 1.51 vs 2.11 per 1000; RR 1.40; 95% CI 0.98-2.00).2
References:
1. Fisher B, et al. Tamoxifen for the prevention of breast cancer: current status of the National
Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 study. J Natl Cancer Inst 2005;
97(22):1652-62.
2. Vogel VG, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast
cancer and other disease outcomes - The NSABP study of tamoxifen and raloxifene (STAR)
P-2 trial. JAMA 2006;205.
Statement 5: Propylactic oophorectomy for BRCA mutation carriers decreases the

risk of breast cancer. (Level II-2, Grade B)
Ten studies investigated breast or gynecologic cancer outcomes in BRCA1/2 mutation

carriers who had undergone risk reducing salpingo-oophorectomy (RRSO). Breast cancer
outcomes were investigated in three nonoverlapping studies of BRCA1/2 mutation carriers,
four of BRCA1 mutation carriers, and three of BRCA2 mutation carriers. Gynecologic cancer
outcomes were investigated in three nonoverlapping studies of BRCA1/2 mutation carriers
and one of BRCA1 mutation carriers. RRSO was associated with a statistically significant
reduction in risk of breast cancer in BRCA1/2 mutation carriers (HR 0.49; 95% CI 0.37-0.65).
Similar risk reductions were observed in BRCA1 mutation carriers (HR 0.47; 95% CI 0.35-
0.64) and in BRCA2 mutation carriers (HR 0.47; 95% CI 0.26-0.84). RRSO was also
associated with a statistically significant reduction in the risk of BRCA1/2-associated ovarian
or fallopian tube cancer (HR 0.21; 95% CI 0.12-0.39). Data were insufficient to obtain
separate estimates for ovarian or fallopian tube cancer risk reduction with RRSO in BRCA1
or BRCA2 mutation carriers.
Reference:
1. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated
with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl
Cancer Inst 2009;101(2):80-7.
Statement 6: In women who have had cancer in one breast (and thus are at higher risk
of developing a primary cancer in the other), prophylactic mastectomy may reduce
the incidence of cancer in that other breast. (Level I, Grade A)
Surgically removing both breasts to prevent breast cancer (bilateral prophylactic mastectomy
or BPM) may reduce the incidence of breast cancer and improve survival in women with
high breast cancer risk, but the studies have methodological limitations. After BPM, most are
satisfied with their decision, but less satisfied with cosmetic results and body image. Many
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August 2010
required additional surgeries. Most experience reduced cancer worry, but because women
may overestimate their breast cancer risk, they need to understand their true risk if
considering BPM. In women who have had cancer in one breast (and thus are at higher risk
of developing a primary cancer in the other) removing the other breast may reduce the
incidence of cancer in that other breast, but there is insufficient evidence that this improves
survival.1
Reference:
1. Lostumbo L, Carbine NE, Wallace J, Ezzo J, Dickersin K. Prophylactic mastectomy for the
prevention of breast cancer. Cochrane Database Syst Rev 2004, Issue 4. Art. No.:
CD002748. DOI: 10.1002/14651858.CD002748.pub2.
Statement 1: There is insufficient evidence to recommend for or against routine

Clinical Breast Examination (CBE) to screen for breast cancer in women 40 years and
older. (Level I, Grade A)
Humphrey, et al. has shown that CBE has a sensitivity of 40-69% and a specificity of 88-
99%.1 The lower specificity as compared to a mammography may result in further work-ups
subjecting women to additional imaging studies and biopsy. In a local study by Pisani, et al.,
of the 138,392 women examined, 3,479 had abnormal CBE and 1,220 completed additional
diagnostic work-ups. However, among these women, only 34 (3%) had cancer, 563 (46%)
had no detectable abnormalities, and 623 (51%) had biopsy results that were benign.2
In the Canadian National Breast Screening Study (CNBSS)-2 trial, Miller, et al. showed no
difference in mortality between mammography with CBE vs CBE alone.3
Nonetheless, despite the evidence, the American Medical Association (AMA), the American
College of Radiology (ACR) and the American Cancer Society (ACS) still support CBE
beginning at age 40. The American College of Obstetrics and Gynecology (ACOG) on the
other hand recommends an earlier initiation of CBE beginning at age 19.
References:
1. Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the
evidence for the US Preventive Services Task Force. Ann Intern Med 2002;137:347-360.
2. Pisani P, Parkin DM, Ngelangel C, Esteban D, Gibson L, Munson M, et al. Outcome of
screening by clinical examination of the breast in a trial in the Philippines. Int J Cancer
2006;118:149-54.
3. Miller AB, To T, Baines CJ, Wall C. Canadian National Breast Screening Study-2: 13-year
results of a randomized trial in women aged 50-59 years. J Natl Cancer Inst 2000;92:1490-9.
Statement 2: Teaching Breast Self Examination (BSE) is not recommended to screen

for breast cancer. (Level I, Grade A)
In the study by Humphrey, et al., BSE has a sensitivity of 12-41% and has been shown to
be age dependent.1 In a Russian trial, although BSE instruction resulted in a significant
increase in the number of breast cancer cases detected, there was no reduction in mortality
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August 2010
(RR 1.07, 95% CI 0.88-1.29).2-3 A randomized controlled trial (RCT) in Shanghai showed no
significant difference in detection rate of breast cancer between those instructed in BSE and
the control (6.5 per 1000 women vs. 6.7 per 1000 women).4 In addition, mortality rate was
similar in both groups (135 of 132,979 and 131 of 133,085, RR 1.03, 95% CI 0.81-1.31).4
The United States Preventive Services Task Force (USPSTF) found adequate evidence that
teaching breast examination is not associated with a decrease in breast cancer mortality
rates.2 In addition, the Canadian Task Force on Preventive Health Care (CTFPHC) also
recommends against teaching BSE to women aged 40 to 69 years. However, the AMA,
ACS, ACOG and American Academy of Family Physicians (AAFP) still support teaching
BSE.
References:
2. Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast
cancer: an update for the US Preventive Services Task Force. Ann Intern Med 2009;151:727-
737.
3. Semiglazov VF, Manikhas AG, Moiseenko VM, Protsenko SA, Kharikova RS, Seleznev IK, et
al. [Results of a prospective randomized investigation [Russia (St.Petersburg)/WHO] to
evaluate the significance of self-examination for the early detection of breast cancer]. Vopr
Onkol 2003;49: 434-41.
4. Thomas DB, Gao DL, Ray RM, Wang WW, Allison CJ, Chen FL, et al. Randomized trial of
breast self-examination in Shanghai: final results. J Natl Cancer Inst 2002;94:1445-57.
Statement 3: Screening mammography is recommended for average-risk women aged

50 to 74 years. (Level I, Grade B)
Mammography is the primary breast cancer screening modality. Mammography screening

has a sensitivity of 77-95%, specificity of 94-97%, and is generally acceptable to women.1
In the meta-analysis by Nelson, et al. (8 RCTs included), it was shown that the rate of
reduction in breast cancer mortality was similar between women who underwent
mammography screening at age 39 to 49 years and women screened at age 50 to 59 years
(15% vs 14%).2 Mandelblatt, et al. showed that mammography screening between the ages
of 50 and 69 years old produced a 17% reduction in mortality (compared to no screening),
whereas extending the age range produced only minor improvements (additional 3%
reduction from starting at age 40 years and 7% from extending to age 79 years).3 Humphrey,
et al., on the other hand, showed that mammography screening at aged 50 to 69 years was
associated with a larger percentage reduction in mortality, as compared to mammography
screening at aged 40 to 49 years (22% vs. 15-17%).1
The following groups support the recommendation to screen using mammography average-
risk women aged 50 to 74 years: USPSTF, CTFPHC, AAFP, American College of Preventive
Medicine (ACPM).
References:
737.
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August 2010
3. Mandelblatt JS, Cronin KA, Bailey S, et al. Effects of mammography screening under
different screening schedules: model estimates of potential benefits and harms. Ann Intern
Med 2009; 151:738-747.
Statement 4: Recommended interval for screening mammography is biennial. (Level I,

Grade B)
A systematic review of RCTs showed that screening every 18 to 33 months versus annually
resulted in the same 23% reduction in breast cancer mortality.1 Mandelblatt, et al. reported
that biennial screening of women aged 50 to 69 years averted 70 to 90% of breast cancer
deaths, with only 2 additional breast cancer deaths averted per 1000 women when
screening was done annually.2 A population-based screening program reported similar 10-
year breast cancer-specific survival rates for women who had annual and biennial screening
mammography.3 A community-based study found that the likelihood of late stage disease at
diagnosis was the same for 2 and 1 year screening intervals.4
The following groups support the recommendation to the biennial mammography: USPSTF,
CTFPHC, AAFP, ACPM. On the other hand, annual mammography is still recommended by
AMA, ACR and ACS.
References:
1. Kerlikowske K, Grady D, Rubin SM, Sandrock C, Ernster VL. Efficacy of screening

mammography. A meta-analysis. JAMA 1995;273:149-54.
Med 2009; 151:738-747.
3. Wai ES, D’yachkova Y, Olivotto IA, Tyldesley S, Phillips N, Warren LJ, et al. Comparison of 1-
and 2-year screening intervals for women undergoing screening mammography. Br J Cancer
2005;92:961-6.
4. White E, Miglioretti DL, Yankaskas BC, Geller BM, Rosenberg RD, Kerlikowske K, et al.
Biennial versus annual mammography and the risk of late-stage breast cancer. J Natl Cancer
Inst 2004; 96:1832-9.
Statement 5: The decision to start regular, biennial screening mammography before

the age of 50 years should be an individual one and take patient context into account,
including the patient’s values regarding specific benefits and harms. (Level II-2, Grade
C)
When screening is started at age 40 years, models estimate that about 60% more false-
positive results occur per 1000 screening examinations than if screening is started at age 50
years.1 Elmore, et al. reported that the cumulative risk for false positive mammography
results reaches 56% for women aged 40 to 49 years.2-3 The Breast Cancer Sceening
Consortium (BCSC) data indicate that although false positive mammography results are
common in all age groups, the rates are highest among women aged 40 to 49 years (97.8
per 1000 women screened). In addition, rates of additional imaging are highest among
women aged 40 to 49 years (84.3 per 1000 women screened) and a lower rate of invasive
cancer is diagnosed per biopsy in women aged 40 to 49 years as compared to women aged
50 to 69 years (19 vs. 38 per 100 biopsies).2
73
August 2010
The CTFPHC concluded that there is insufficient evidence to recommend for or against
mammography in women 40 to 49 years old. However, the ACOG still recommends
mammography every 1-2 years for women aged 40 to 49 years and annually for women
aged 50 and older.
References:
Med 2009; 151:738-747.
737.
3. Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk of false
positive screening mammograms and clinical breast examinations. N Engl J Med
1998;338:1089-96.
Statement 6: For women less than 50 years old, digital mammography is superior to
film mammography. (Level II-2, Grade C)
The Digital Mammography Imaging Screening Trial (DMIST) demonstrated that digital
mammography is more accurate when used in women under age 50 and those with dense
breasts.1 Tosteson, et al. further showed that age-targeted digital screening (for women < 50
years old) appears to be cost-effective. It increases the number of screen-detected cancers
and lead to fewer cancer deaths when compared with film screening.2
References:
1. Pisano ED, Gatsonis C, Hendrick E, et al. Digital mammographic imaging screening trial
(DMIST) investigators group. Diagnostic performance of digital versus film mammography for
breast cancer screening. N Engl J Med 2005;353:1773-1783.
2. Torteson ANA, Stout NK, Fryback DG, Acharyya S, Herman B, Hannah L, et al. Cost
effectiveness of digital mammography breast cancer screening: results from ACRIN DMIST.
Ann Intern Med 2008;148(1):1-10.
Statement 7: Screening mammography should be stopped at age 74. (Level II-2, Grade
C)
A case-control study of women receiving mammography showed decreased mortality in

women younger than 75 years, but no survival benefit in women older than 74 years.1
In addition, although studies show that screening decreased mortality, the beneficial effect
appeared with a lag time of 4 to 5 years after screening.2
A cost analysis study by the USPSTF showed that mammography was cost effective for
women up to 80 years of age, but only in healthy patients with the greatest life expectancy.3
References:
1. Van Dijck JA, Verbeek AL, Beex LV, et. al. Mammographic screening after the age of 65
years, evidence for a reduction in breast cancer mortality. Int J Cancer 1996;66(6):727-31.
74
August 2010
2. Nystrom L, Andersson L, Bjurstam B, Frisell J, Nordenskjold B, Rutqvist LT. Long term effects
of mammography screening: updated overview of the Swedish randomized trials. Lancet
2002; 359: 909-919.
3. Mandelblatt JS, Cronin KA, Bailey S, et. al. Effects of mammography screening under
Med 2009; 151: 738-747.
Statement 8: Screening for breast cancer using breast magnetic resonance imaging
(MRI) is not recommended in the general population of asymptomatic, average-risk
women. (Level III, Grade C)
Literature shows a wide range of specificity for breast MRI. The additional abnormalities
detected on MRI may result in a follow-up examination or recommendation for biopsy.1
Reference:
1. Woodard PK, Bluemke DA, Cascade PN, Finn JP, Stilman AE, et al. ACR practice guideline
for the performance of contrast-enhanced magnetic resonance imaging (MRI) of the breast. J
Am Coll Radiol 2006;3(9):665-76.
Statement 9: High risk women should start annual screening mammography

beginning at age 30. (Level II-2, Grade B)
De Bock, et al. identified family history risk factors that are highly associated with a younger
age of breast cancer diagnosis: (1) at least 2 female first degree relatives with breast cancer,
(2) at least 2 female 1st or 2nd degree relatives with breast cancer under the age of 50, (3) at
least 1 female 1st or 2nd degree relative with breast cancer under the age of 40, and (4) any
relative with bilateral breast cancer.
In the presence of at least 2 of these characteristics, the HR for developing breast cancer at
the age of 30 was 10.62. This study provided a strict criteria of individuals who would truly
benefit from annual breast cancer surveillance at an early age.1
The AAFP and ACPM also recommend the initiation of annual screening mammography
beginning at age 30 for high risk women.
Reference:
1. De Bock GH, Jacobi CE, Seynaeve C, Krol-Warmerdam EMM, Blom J, Aseren CJV, et al. A
family history of breast cancer will not predict female early onset breast cancer in a
population-based setting. BMC Cancer 2008;8:203.
Statement 10: Women at high risk for developing breast cancer should receive annual
MRI as an adjunct to mammography. (Level III, Grade C)
Kriege, et al. have found that MRI, when used for screening of high risk women, has a
sensitivity of 71-100% (vs. 16-40% for mammography alone) and a specificity of 81-97%.1
75
August 2010
The ACR recommends MRI screening for the following:

! Women with a BRCA mutation
! Women with a first-degree relative who has a BRCA mutation
! Women with a 20-25% or greater lifetime risk for breast cancer, based on BRCAPRO or
other risk models that depend largely on family history
! Women exposed to chest radiation between the ages of 10 and 30 years
! Women with Li-Fraumeni syndrome, and first degree relatives of women with this
syndrome
! Women with Cowden and Bannayan-Riley-Ruvalcaba syndromes, and first degree
relatives of women with these syndromes
Reference:
1. Kriege M, Brekelmans CT, Boetes C, et al. Magnetic resonance imaging screening study
group. Efficacy of MRI and mammography for breast cancer screening in women with a
familial or genetic predisposition. N Engl J Med 2004; 351:427-437.
Statements 11-12: Recommendations for women with a history of chest irradiation

between ages 10 and 30 years include the following:
11: For women previously treated with irradiation of at least 20 Gy to the mantle,
minimantle, mediastina, chest or axillary fields, early CBE from the age of puberty
until age 25 years, and then every 6 months is recommended. (Level III, Grade C)
12: For the same group of women, an annual mammography and an adjunct breast
MRI starting at age 25 or 8 years after radiation, whichever is last, should be done.
(Level III, Grade C)
The effectiveness of the standard mammogram in detecting preinvasive and invasive breast
cancer is known to be relatively poor in young women due to the density of breast tissue in
this age group, increasing the importance of MRI in the detection and diagnosis of breast
cancer in the younger women.1
The Childhood Oncology Group (COG) supports the above recommendations.
Reference:
1. Taylor AJ, Taylore RE. Surveillance for breast cancer after childhood cancer. JAMA
2009;301(4): 435-436.
Statement 13: For women with a personal history of breast cancer, annual
mammography is recommended after the date of diagnosis but annual MRI can also
be considered. (Level III, Grade C)
Posttreatment follow-up of breast cancer patients continues to be controversial despite

almost 2 decades of research. The research dose not show that more frequent surveillance
mammograms are beneficial and guidelines recommend routine surveillance mammograms
annually.1
76
August 2010
MRI can detect occult malignancy in the contralateral breast in at least 3-5% of breast
cancer patients.2
Reference:
1. Grunfeld E. Optimizing follow-up after breast cancer treatment. Curr Opin Obstet Gynecol
2009;21(1):92-6.
Am Coll Radiol 2006;3(9):665-76.
Statement 14: MRI should routinely be used for the contralateral breast at the time of
diagnosis of breast cancer in all women. (Level III, Grade C)
MRI can detect occult malignancy in the contralateral breast in at least 3 to 5% of breast
cancer patients.1
Reference:
Am Coll Radiol 2006;3(9):665-76.
Statement 15: Sonomammography can be considered as a complementary tool to

mammography. (Level II-2, Grade B)
Sonomammography is used a complementary tool for mammography in the following

manner: (1) to characterize lesions initially seen on mammography, (2) to identify palpable
masses than cannot be seen on mammograms, (3) to serve as an imaging tool for the young
and the pregnant who are unable to undergo mammography, and (4) to scan dense
breasts.1
By adding sonomammography to mammogram, overall cancer detection rate is increased by

17% and a 37% increase in overall tumor detection. The sonomammography has the added
benefit of aiding in the differentiation between benign and malignant masses based on the
shape of the mass’s image. Simple cysts are diagnosed with 98% to 100% accuracy, yet
more complex cysts yield a lower sensitivity.1
Reference:
1. Nover AB, Jagtap S, Anjum W, Yegingil H, Shih WY, et al. Modern breast cancer detection:
A technological review. Int J Biomed Imaging 2009;2009:902326. Epub 2009.
Statement 16: Scintimammography (SMM) can be considered as a complementary

tool in the evaluation of patients with breast lesions. (Level II-2, Grade B)
A total of 283 consecutive women (mean age 53+/-8 years) with microcalcifications (MC)
identified on X-ray mammograms (MRx) underwent (99m) Tc-sestamibi SMM. Scintigraphic
77
August 2010
images were acquired 10 minutes after the IV injection of (99m) Tc-sestamibi (740 MBq).
Planar images of both breasts were simultaneously obtained in the lateral prone position and
in the anterior and oblique projections using a dual head camera. Sixty-nine women
underwent surgery, whereas the remaining 214 patients had completely negative follow-up
for 5 years (a 5-year follow-up period is considered the "gold standard" for diagnosing
benign lesions). Histology demonstrated 32/69 primary breast carcinomas (prevalence of
disease: 11% of all the 283 patients) and 37/69 benign lesions. The receiver operating
characteristic (ROC) statistical technique was employed to compare the diagnostic value of
MRx alone to that of combined MRx and SMM. The detected difference between the areas
under the MRx ROC curve (area=0.72, standard error 0.052) and the MRX and SMM ROC
curve (area=0.86, standard error 0.039) was statistically significant (p<0.01). Moreover, the
combination of MRx and SMM provided a significant improvement of the negative predictive
value (NPV=98%) for MC with low-suspicion of malignancy at MRx.1
Reference:
1. Grosso M, et al. Comparison between 99mTc-sestamibi scintimammography and X-ray

mammography in the characterization of clusters of microcalcifications: a prospective long-
term study. Anticancer Res 2009;29(10):4251-7.
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August 2010
APPENDIX
LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION
LEVEL DEFINITION
I Evidence obtained from at least one properly randomized controlled trial
Evidence obtained from well-designed controlled trials without
II-1
randomization
Evidence obtained from well-designed cohort or case-control analytic
II-2
studies, preferably from more than one center or research group
Evidence obtained from multiple time series with or without the
II-3
intervention.
Opinions of respected authorities, based on clinical experience;
III
descriptive studies and case reports or reports of expert committees.
GRADE DEFINITION
A There is good evidence to support the recommendation of the practice.
B There is fair evidence to support the recommendation of the practice.
There is insufficient evidence to recommend for or against the inclusion of
C
the practice.
There is fair evidence to support the recommendation that the practice be
D
excluded.
There is good evidence to support the recommendation that the practice
E
be excluded.
A good practice point (GPP) is a recommendation for best practice based
GPP
on the experience of the Working Group.
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"#$%&!'()%!

Society of Gynecologic Oncologists

Medicine is a dynamic field, it is continuously evolving. This is especially

Rey H. delos Reyes, MD, MHSA

This publication of the Society of Gynecologic Oncologists of the

Efren J. Domingo, MD, PhD

REY H. DELOS REYES, MD, MHSA

MA. CYNTHIA F. TAN, MD

MA. LILIBETH L. SIA SU, MD

MARY CHRISTINE F. PALMA, MD

EFREN J. DOMINGO, MD, PhD

PHILIPPINE BOARD OF GYNECOLOGIC ONCOLOGY

NATIONAL CAPITAL REGION REGION I

1. Jacques F, et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence

II. RISK FACTORS

Statement 1: Human papilloma virus (HPV) infection is the necessary cause of

A meta-analysis by the International Agency for Research on Cancer (IARC) included a

1. Franceschi S. The IARC commitment to cancer prevention: The example of

1. Muñoz N, Franceschi S, Bosetti C, et al. Role of parity and human papillomavirus in

Statement 4: The risk of squamous cell carcinoma increases in current smokers

Malignant transformation of HPV 16 immortalized human endocervical cells by cigarette

1. International Collaboration of Epidemiological Studies of Cervical Cancer. Carcinoma of

1. Smith JS, Munoz N, Herrero R, Eluf-Neto J, Ngelangel C, Franceschi S, et al. Evidence

1. International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical

Statement 8: The risk of invasive cervical carcinoma increased with lifetime

1. International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical

1. International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical

1. Dos Santos IS, Beral V. Socio-economic differences in reproductive behaviour. IARC

III. PRIMARY PREVENTION

Statement 1: Total abstinence prevents HPV infection. (Level II-2, Grade A)

Statement 4: Vaccination against HPV 16/18 is efficacious against persistent HPV

1. Muñoz N, Manalastas R Jr, Pitisuttithum P. Safety, immunogenicity, and efficacy of

Statement 5: Oral supplementation with folic acid, beta carotene, or vitamin C

IV. SECONDARY PREVENTION

Statement 1: Screening via regular gynecologic examinations and cytologic test

1. Sigurdsson K. Effect of organized screening on the risk of cervical cancer. Evaluation of

A meta-analysis of 8 studies identified by the authors to be methodologically sound

An RCT of 6555 nonpregnant women, aged 35 to 65 years, recruited through community

1. Sankaranarayanan R, Esmy PO, Rajkumar R, et al. Effect of visual screening on cervical

Statement 4: Screening should begin approximately 3 years after the onset of

The 2005 World Health Organization-Western Pacific Regional Office (WHO-WPRO)

1. Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population

1. Stokes-Lampard H,Wilson S,Waddell C, Ryan A, Holder R, Kehoe S. Vaginal vault

Statement 9: Discontinue cervical cancer screening between 65 years and 70

The likelihood of testing HPV-positive in conjunction with co-testing is population specific

Statement 12: Annual gynecologic examination is recommended regardless of the

Regardless of the frequency of cervical cytology screening, physicians also should

1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number

1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number

1. 2006 CDC Guidelines on Sexually transmitted infections (MMWR Recommendations and

V. FIGO 2009 CLINICAL STAGING FOR CERVICAL CANCER

I The car cin o ma i s s tri ctl y c on fine d to th e c ervi x

B. MESENCHYMAL TUMORS & MIXED EPITHELIAL-MESENCHYMAL TUMORS

VII. GENERAL GUIDELINES IN THE DIAGNOSIS AND MANAGEMENT OF

1. Cervical cancer is diagnosed by biopsy1.

! The overall incidence of epithelial ovarian cancer varies from 9 to 17/100,000.

II. RISK FACTORS

Approximately 10 to 15% of all epithelial ovarian cancers have a hereditary

In a pooled analysis of 8 case-control studies, among nulliparous, subfertile women,

Statement 4: Long-term use of unopposed estrogen or of estrogen plus progestin

The National Institute of Health (NIH)-American Association of Retired Persons (AARP)

Statement 5: Endometriosis is linked to an increased risk of epithelial ovarian

Several studies have linked endometriosis to an increased risk of epithelial ovarian