Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Cervical Smears.
Sammy .K.
Facilitator: Patricia Muthaura
Objectives
Review HPV and its effects on
cervical epithelium.
Management of abnormal cervical
smears.
Value Addition in Pathological
Assessments.
Nonenveloped ds DNA
virus1
HPV
>100 types identified2
~3040 anogenital2,3
1520 oncogenic*,2,3
HPV 16 and HPV 18 types
account for the majority of
worldwide cervical
cancers.4
Nononcogenic** types
HPV 6 and 11 are most
often associated with
external anogenital warts.3
1. Howley PM, Lowy DR. In: Knipe DM, Howley PM,
eds.risk;
Philadelphia,
Pa: Lippincott-Raven; 2001:21972229.
*High
**
Low risk
2. Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930934. 3. Wiley DJ, Douglas J, Beutner K, et al.
Clin Infect Dis. 2002;35(suppl 2):S210S224. 4. Muoz N, Bosch FX, Castellsagu X, et al. Int J Cancer.
2004;111:278285.
Reprinted from J Virol. 1994;68:45034505 with permission from the American Society for Microbiology
Journals Department.
Pathogenesis
HPV is epitheliotropic.
Episomal state
Integrated state
An important factor in
the early stages
following infection is
the individual's
susceptibility to
oncogenic HPV types,
which is determined by
the host's immune
system.
Cervical Surface
Mature
Squamous
Layer
Squamous
Layer
Parabasal
Cells
Viral Assembly
(L1 and L2)
Viral DNA Replication
(E6 and E7)
Episomal Viral DNA
in Cell Nucleus
(E1 and E2, E6 and E7)
Infection of Basal
Cells (E1 and E2)
Basal (Stem)
Cells
Basement Membrane
Normal
Epithelium
Infected
Epithelium
1. Frazer IH. Nature Rev Immunol. 2004;4:4654. Adapted with permission from Nature Reviews
Immunology 2004 Macmillan Magazines Ltd.
Cervical Anatomy
Location Of SCJ
.Abnormal Screen
Result.
Classification
Management Strategies.
Bethesd
a
CIN
Dysplasi
a
ASCUS
Cellular
Atypia
Unspecifi
ed
cellular
changes
LGSIL
CIN 1
Mild
dysplasia
HGSIL
CIN 2,
CIN3
Moderate
/Severe
dysplasia
Availability of
resources
Treatment resources
Age
Fertility desires
Grade and extent of
lesion
Motivation for follow up
Expertise
AIMS of Colposcopy
1.To determine the precise geographical
anatomical position of the TZ
2.To confirm or refute the cytological
suspicion of cervical intraepithelial
neoplasia (CIN)
3.To recognize or rule out invasive cancer
4.To recognize or rule out glandular disease
5. To facilitate treatment of and monitor
progression or regression of CIN
Satisfactory Colposcopy
Satisfactory colposcopy-indicates that
the entire SCJ and the margin of any
visible lesion can be visualized with
the colposcope
ECC-Endocervical evaluation by
cytology or curettage is sometimes
used when colposcopy is
unsatisfactory or when an
endocervical lesion is suspected
Colposcopy in Post
Menopause
Cervical and vaginal epithelium very
thin, allowing visualization of the
subepithelial capillaries, which may
appear red and atypical
Use of acetic acid is not as effective
in detecting premalignant disease
short course (34 weeks) of
intravaginal oestrogen cream
Colposcopy in Pregnancy
cervix is larger, oedematous and more
vascular
Cervix usually covered by mucus,
which is difficult to remove
Decidual changes of the cervical
epithelium can mimic cancerous
epithelium
vascular changes associated with
abnormality may be more pronounced
What is ASCUS?....
Atypical Squamous cells of
Undetermined Significance.
Lowest risk of developing into
cervical cancer(0.1 to 0.2%.)
Initial Approach:-3 pronged.
Repeat Cytology
HPV testing
Colposcopy
ASCUS
Reflex testing- Testing for HPV at initial screen
Prevalence of HPV DNA changes with age
among those with ASCUS
21 yrs and over
Effective in older women as less women will be
referred for colposcopy
Initial evaluation
2 repeat cytology exams six months apart
HPV testing
Colposcopy
Management Algorithm
ASCUS in Special
populations
Pregnancy
Postmenopausal
Pregnancy-Defer
Colposcopy to 6 weeks post
partum, ECC is
unacceptable
Postmenopausal Managed
as general population
Women 21-24yr- Cytology
is preferred, Reflex testing
acceptable , if HPV neg
,cytology in 12 months.
ASCUS -H
Special (Where HSIL
cannot be ruled out)
Colposcopy advised
When CIN 2,3 not seen
at colposcopy HPV
testing at 12 months or
repeat cytology at 6
and 12 months
On repeat cytological
testing refer to
colposcopy if
HPV +
ASCUS and greater
LGSIL
Follow up
Cytological diagnosis
LGSIL (2%) of women
LGSIL is highly
predictive of HPV
infection
85% of patients with
LGSIL will have HPV
positve screen
LGSIL
ASCUS/LGSIL Triage
Study (ALTS)
ALTS TRIAL
Result
Stoler, M.H. and Schiffman, M., Interobserver Reproducibility of Cervical Cytologic and Histologic
Interpretations: Realistic Estimates From the ASCUS-LSIL Triage Study, Journal of the American Medical
Association, 285(11), Mar. 21, 2001.
HGSIL
0.45% of cytology
reports
75% will have biopsy
confirming CIN 2/3
1-2% invasive cancer
An immediate
LEEP/Colposcopy /or
ECC is acceptable
except in pregnancy
HGSIL
Categories
AGC NOS
AGC-favour neoplasia
AIS -Adenocarcinoma
in Situ
Part 1
A 21 year old girl has
HGSIL on cytology
Colposcopy satisfactory and
biopsy taken at 11 oclock
Result CIN2
Mgt:
a)LEEP
b)Pap Smear rpt at 6 and 12
months
c)Pap + Colpo in 6 and 12
months
d)HPVDNA in 12 months
Part 2
If her biopsy showed
CIN3 what would be
the next step
a)LEEP
b)Follow with Pap in 6
-12 months
c)Pap and colposcopy
in 6 -12 months
d)HPV DNA in 12
months
Commercial Break..
A= Accurate , Little
Precision
B= Precise but not
accurate
C=No accuracy ,No
precision
D=Accurate and
Precise
LAST(Lower Anogenital
Squamous Terminology)
Basis of final Consensus
Limiting tiers
2 tier:- Higher Kappa
Statistic of 0.3 to 0.71
3 tier :-Kappa statistic
of 0.12 to 0.58.
.Basis Of Consensus.
Biomarkers
P16
Ki 67
Pro Exc
L1
HPV 16,18 m-RNA
Telomerase
HPV genotyping
Biomarkers
A lesion that was
problematic due to
somewhat tangential
sectioning was variably
called CIN1 as well as
CIN 2 on H&E (A).
Typical p16 positivity in
a continuous from the
bottom up pattern
indicative of high-risk
HPV E7 induction of p16
expression.
Clinical Application
New tier system
LGSIL=CIN1 AND
CIN2(P16 Negative)
Thanx!