6. Production of estrogens by ovary stimulates
maturation of the cervical and vaginal squamous
mucosa and formation of intracellular glycogen
vacuoles in the cells
Glycogen provides a substrate for various
endogenous vaginal aerobes and anaerobes, but
particularly lactobacilli, which are the dominant
microbial species in the normal vagina
Lactobacilli produce lactic acid, which maintains
the vaginal pH below 4.5, suppressing the growth
of other saprophytic and pathogenic organisms
10. Cervicitis
Marked cervical inflammation
produces reparative and reactive
changes of the epithelium and
shedding of atypical-appearing
squamous cells, and therefore may
cause an abnormal Pap test result
12. Endocervical polyps:
2 to 5 % of adult women
Common benign exophytic growths that arise
within the endocervical canal
CLINICAL FEATURES: Irregular vaginal ‘
spotting’
GROSS: small, sessile “bumps” to large
polypoid masses
MICRO: dense fibrous stroma covered with
endocervical epithelium
Simple curettage OR excision.
14. Worldwide, cervical carcinoma is the third
most common cancer in women
remarkable benefits of effective screening,
early diagnosis, and curative therapy
15. Risk factors
The risk factors for cervical cancer are related
to both host and viral characteristics such as
HPV exposure, viral oncogenicity, inefficiency
of immune response, and presence of co-
carcinogens
16. Major risk factors:
1. Early age at first sexual
intercourse,
2. Multiple sexual partners
3. Male partner with previous
multiple sexual partners
Sexually
transmitted
agent ---
HPV
Risk factors
17. Other risk factors:
Oral contraceptives,
Cigarette smoking,
Parity,
Family history,
Genital infections,
Lack of circumcision of male
partner - smegma
20. HPV
Infect immature basal cells of the squamous
epithelium
Mature cells are arrested in the G1 phase of
the cell cycle, but they continue to actively
progress through the cell cycle when infected
with HPV, which uses the host cell DNA
synthesis machinery to replicate its own
genome
21.
22. SQUAMOUS
DIFFERENTIATION
Infection
basal cells
Early (Non-structural)
protein synthesis
LATENTLATENT
INFECTIONINFECTION
Condyloma
or CIN-1
[koilocytosis]
Integration[ISH]
+ Oncogenes
- Tumour suppressor genes
INVASIVE
CARCINOMA
Productive
DNA synthesis
Late [capsid]Late [capsid]
protein synthesisprotein synthesis
[IH][IH]
Viral
particles [EM]
DesquamationDesquamation
transmissiontransmission
HPV life cycle
Episomal DNA
replication (ISH)
23.
24. Pathogenesis
E6 protein promotes
upregulates telomerase and bind to p53
promote its degradation
E7 protein binds the hypophosphorylated
(active) form of RB and promotes its
degradation via the
proteasome pathway,
28. Cytopathic effects of HPV
Nuclear enlargement, nuclear
pyknosis or
hyperchromaticity,
anisocytosis, multinucleation,
and
perinuclear cytoplasmic
vacuolization
(a) Histological features of a
lesion is classified as LSIL
(b) Cytological features of
LSIL
29. Electron microscopy
(a) intranuclear
aggregates of HPV
in a koilocytotic,
superficial cell of an
HSIL. The
marginated nuclear
chromatin is
agglutinated,
cytoplasmic
substance displays
vacuolar
degeneration (vd)-
koilocytotic
ballooning on light
microscopy
(b) Higher
magnification
30. Koilocytes – perinuclear halo caused by E5 that localizes to the membranes of the
endoplasmic reticulum.
34. Pathogenesis
of cervical
neoplasia
Sexual activity
HPV exposure
Cervical transformation zone
Ectocervix Squamous epithelium
Low grade
Low-risk HPVs
6,11,42-44,
High grade
High-risk HPVs
16,18,31,33,35
Smoking , oral contraceptives, high parity, altered
immune status, host gene alterations, time
Endocervical columnar epithelium
Glandular intraepithelial lesion
(adenocarcinoma-in-situ)
High-risk HPVs
INVASIVE SQUAMOUS CARCINOMA ADENOCARCINOMA
rare
35. The diagnosis of SIL is based on
identification of nuclear atypia
characterized by nuclear
enlargement, hyperchromasia (dark
staining), coarse chromatin granules,
and variation in nuclear size and
shape
36.
37.
38. The grading of SIL into low or high grade is
based on expansion of the immature cell layer
from its normal, basal location
LSIL does not progress directly to invasive
carcinoma and in fact most cases regress
spontaneously; only a small percentage
progress to HSIL
50. The pap test
The Pap test is considered by many to be the
most cost effective cancer reduction program
ever devised
1928- George N. Papanicolaou
1940s- screening
programmes started
54. Approximate lifetime risks of acquiring
HPV & Death by cervical cancer:
HPV
HPV
75%
Population
50%
High-risk
HPV 10%
Persistent
High-grade
CIN
1. 3%
Invasive
Carcinoma
0. 4%
DEATH
55. Prognosis:
5 - year survival rate:
Stage - I = 80 to 90 %,
Stage - II = 75%,
Stage - III = 35% ,
Stage - IV = 10 to 15%.
56. Gardasil (Merck & Co., Inc.)-
quadrivalent- HPV 6, 11, 16,18
Cervarix (GlaxoSmithKline)-
bivalent - HPV 16 and 18
They have shown extraordinary
efficacy in preventing type-specific
histologic CIN 2,3 lesions
Administered in three doses to
females ages 9 to 26 years before
the initiation of sexual activity
58. WHO comprehensive cancer
prevention and control
Primary prevention- Education to reduce high-risk sexual
behavior to limit HPV transmission/acquisition
Delay age of first sexual intercourse
Condom use, limit number of partners, change in sexual
behavior
HPV vaccination
Early detection (secondary prevention)
Scre e ning : Identify and treat precancerous lesions before
they progress to cervical cancer
Early diag no sis : Identify and treat early cancer while the
chance of cure is still good (reduces cervical cancer mortality)
Tertiary prevention:
Tre atm e nt o f invasive cance r
Palliative care
Health Systemstrengthening
