Case 16 – Intraepithelial and Neoplastic Lesions of the Cervix
Discussion with Dr. Gil Gonzalez
40 year old G3P3 (3003) consulted because of
postcoital bleeding of 8 months duration. First delivery at age
18; FPM: OCP – 2008 up to present. She had regular menses.
Pap smear in 2011 showed ASCUS. Pelvic exam: cervix –
pink, with erosions between 9 and 12 o’clock, which easily
bleeds to touch. IE: vaginal wall- smooth; cervix – firm, long
and closed; uterus – normal-sized, anteverted, mobile; adnexa
(-) for mass nor tenderness.
Student’s Recitation (Ask 3 Questions):
• Does the patient have past HPV vaccination?
o Decreases the risk of cervical malignancy if given
at 10-14 years old since we would prefer to give
the vaccine prior to exposure.
o Age range of 10-14 years old have the highest
immune response towards the vaccination.
• What is the significance of first delivery at 18 years
old?
o The patient will be at higher risk of cervical
malignancy
o Early age of coitus would have a higher risk of
malignancy since there is earlier exposure to
possible STDs
o Generally, the more pregnancies, the more at risk
for cervical cancer.
• Post-coital bleeding: when was her LMP?
o To differentiate it from other causes of bleeding
• First Pap’s Smear should be:
o Within 2-3 years after initiating sexual activity
 3-5 years after the initiation of sexual activity,
cervical dysplasia might have already taken
place.
o Public health view: Don’t screen below age 21
since there is a lower incidence and it wouldn’t be
“cost-effective”. However, we are looking at the
patient individually and we would think of an
individual protection.
• Sexual partner: How many partners and if the partner
is also monogamous.
o She may be at risk for STDs
• Smoking
o Indirect risk for cervical cancer
o Chemical smoke contains over 3,000 chemicals
in tobacco smoke
 About 50-60 of them are known carcinogens
and these have been found in endocervical
mucus as well.
 Thus, smoking is a risk factor for cervical
cancer
• What causes cervical cancer?
o Human Papilloma Virus: may be contracted via
sexual contact
 Vaginal contact is not a requirement.
 The virus is passed via skin-to-skin (direct)
contact
 A microabrasion on the skin of the vaginal or
cervical mucosa is enough to pass the virus.
• PE was normal except for the erosions at 9-12
o’clock. Seeing this kind of cervix, what would be the
next step for her?
o Pap’s Smear would be done. If it shows ASCUS
(Atypical Squamous Cell of Undetermined
Significance) again, do a colposcopy
 Biopsy is practical but colposcopy is ideal
o Do a colposcopy first to identify the most
abnormal area since it is magnified. It is a
directed biopsy and it would allow a higher yield.
M 1
• Sexual activity:
o Areas of trauma: Introitus (Fourchette – most)
• HPV is in the center of things, whatever form of
neoplasia it may be. Without this, it cannot happen.
o Other factors that might have facilitated cancer:
 Teenage sexual activity
 Multiparity
 Sexual promiscuity
 OCP
 Smoking
 Male partner who had a partner who died of
cervical cancer
 STDs
o Again, microtrauma is the only one needed to
have the disease. A simple break in the layers of
the epithelium.
• Layers and the Pathogenesis of HPV in these layers
o Parabasal
 Stays in the basal cell after trauma and stays
there
o Intermediate
 Contains the virus that has inserted its DNA
to the cells, making it a factory
o Superficial
 The cell dies and releases the virions that
may infect the same area or another partner.
• Prevention:
o Primary Prevention
 Mutually monogamous within the bonds of
marriage
 Vaccination
• Get it before they are exposed!
• But the antibodies are only at the
basement membrane and it won’t be at
the layers but it would be present in the
transudates from the serum that would
penetrate the layers.
• HPV Vaccination Principles:
o Younger age is better:
 They develop the highest level of antibodies
as compared to others.
 Natural protection  not enough to produce
protection
• Because an HPV infection is a purely
intraepithelial infection and does not
become systemic. Thus, it would not be
acted upon by the antibodies of natural
protection.
• Development of antibodies in
immunocompetent individual may have
cleared the virus in the current infection
but they will not produce adequate have
protection against reinfection. That said,
they may still get infected by the same
virus type.
• Immunization works because they
produce a significantly higher levels of
antibodies that would be present in the
transudates from the basal layer.
 Basically, it is dependent on the immune
system of the person who will be vaccinated
and their capability to produce high levels of
antibodies.
Cervical Cancer Lecture from Dr. Gonzalez
• Local Data:
o Cervical cancer is no. 2 cause of cancer, second
only to breast cancer.
o About half of the new cases would be the number
of deaths in the same year.
 • Established and Potential Co-factors involved in HPV
carcinogenesis
o HPV
o Other risks:
 High parity
 OCP
• Everts the endocervical epithelium and
exposes it to infection
 Smoking
• As a promoter or a fertilizer
 HIV
 Co-infection with other STIs
• Inflammation to the vagina and cervix
which predisposes it to easier trauma.
 Diet
 Endogenous Hormones
 Genetic Factors
• Human Papillomavirus
o Relatively small virus circular dsDNA
o Relatively small virus containing circular double
stranded DNA within a spherical shell.
o Infect cutaneous epithelium and mucosal
epithelium (cervical and other anogenital
mucosa)
• HPV  most prevalent STD (nearly 300 million
people have HPV infection and may be undetected 
asymptomatic carriers)
• Cervical cancer is a relatively rare outcome for a very
common disease.
• HPV  a necessary cause of cervical cancer
o HPV 18 and cervical adenocarcinoma in the
Philippines, Oncogenic HPV DNA and cervical
cancer in Costa Rica, HPV DNA and cervical
cancer in Bangkok. (RR/OR > 500)
• Worldwide: every 2 minutes a woman dies of cervical
cancer.
• Cervical cancer in the Phi
o ASR: 11/100,000
o 7200 new cases yearly
o 2700 deaths yearly
o 56% of Filipino women with cervical cancer will
die within 5 years
o About 2/3 of cervical cancer is diagnosed in the
advanced stage, where mortality is high
 There is no organized widespread campaign
addressing the disease.
• HPV types:
o 16 and 18  most common
o 45 and 31 with 16 and 18  top 4.
• Vaccination would offer cross protection to other
strains
• HPV Life Cycle in the Cervix (Check above)
o Microabrasion is important
• HPV escapes the immune system:
o Local infection, no viremia
o HPV does not kill keratinocytes, no inflammation
o Free virus particles are shed from mucosal
surfaces with poor exposure to antigen
presenting cells (APC)
• Primary and secondary prevention
o Primary prevention
 Measures used in people with no clinical
evidence of disease
 Avoidance of risk factors
 HPV vaccination
o Secondary prevention
 Screening, early detection (Pap smear, VIA)
 Actions to slow or stop the progress of a
disease during its early stages.
• 27 vaccine preventable diseases
M 2
o Anthrax
o Cervical cancer
o Diphtheria
o Hep A
o Hep B
o Etcetera
• HPV L1 Virus-like particle (VLP) Vaccine Synthesis
o L1 gene of HPV DNA  inside HPV  L1 gene
inserted into a plasmid  transcription mRNA 
translation  capsid proteins  empty viral
capsid (VLP)  elicits immune response in host
• HPV prevalence bar graph
o 16-21
• How long will the protection last?
o So far, 9.4 years (start of the vaccine)
o Cervicovaginal secretions
 High antibody levels
o Projections:
 HPV 16/18 antibody levels predicted to
remain well above the natural infection level
for at least 20 years.
• Quadrivalent vaccine
o Australia  part of the national vaccination policy
and they targeted the 12-14 year old age group.
 Less cases of cervical cancers and genital
warts
o Vaccination in 12 years old may have results
seen in 15 years time.
o 12-26 years old  5 years time.
o 12-55 years old  3 years time assuming 80%
coverage
• Guidelines on HPV Vaccine
o Age 9-45 years old (MS); age 10 onwards (GSK)
o Females
o Prophylaxis
o Dose: MSD – 0, 2, 6 months; GSK – 0, 1, 6
months
o Screening should continue
o Pap, HPV DNA testing not necessary prior to
vaccination
o Males – prevention of genital warts only, not in
context of cervical cancer prevention.
• Increased screening has greatly reduced the
incidence of cervical cancer in England:
o As the number of women screened went up, the
incidence of cervical cancer went down due to
good coverage.
• Summary:
o Current knowledge
 24-48 hours Latent period may be as short
as 24-48 hours  active growth  cell-
mediated immune response
• No viremia
• No inflammatory response
• No cytokine
• No host cell damage
 6-12
 12-18:
o Progression of cervical carcinogenesis
 15-20 years from normal then trouble.
There’s a lot of time for secondary
prevention/screening.
o Brachytherapy
UST wins GAME 1! Go USTe! Go USTe! Go USTe! Go! Go! Go! Go!
These are just notes taken down by a nocturnal medical student at 7 AM in the
morning. Study at your own risk.