Cervical cancer is caused by HPV infection and is the leading cause of cancer deaths in many developing countries. HPV is present in over 99% of cervical cancers. Risk factors include young age of first sexual activity, multiple partners, early pregnancy, and smoking. Precancerous lesions usually develop over 10-15 years. Cervical cancer spreads locally through the cervix and vagina, and can metastasize to nearby lymph nodes and distant sites like the lungs and liver. Diagnosis involves identifying dysplastic cervical cells, and treatment depends on the cancer stage.

1. Cervix--cancer

2. • high in Latin America, southern and eastern Africa,
India, and Polynesia; in many of these developing
countries, cervical cancer is the leading cause of cancer
deaths among women.
• Molecular and human epidemiologic studies have
demonstrated a strong relationship between HPV,
cervical intraepithelial neoplasia (CIN), and invasive
carcinoma of the cervix;
• HPV can be identified in more than 99% of cervical
cancers, and infection with HPV is now accepted as a
necessary cause of most cervical cancers

3. Aetiology,predisposing risk factors
• Average age 35-45years. Precancerous lesions occur 10-
15years earlier.
• Women who have coitus before the age of 18
• multiple sexual partners
• Delivery of first baby before the age of 20years
• Multiparity with poor birth spacing
• Poor personal hygiene
• Poor socio economic status

4. • Smoking,drug abuse,alcohol are immunosuppressive
• circumcised males have a lower incidence of HPV infection than
uncircumcised males and a correspondingly lower incidence of
cervical cancer in their female partners.
• STD,HSV-2,HPV(16.18,31,33),condylomata,HIV-infected women
have an increased incidence and are more likely to have persistence
of cervical HPV infection, also tend to have a faster rate of
progression to high-grade CIN.1
• immunosuppressed individuals
• Having preinvasive lesion
• Who don’t come for regular health check up and pap test
• COC and progesterone use for >8years
• women exposed to in utero to diethylstilboestrol

5. Pathophysiology
• HPV infection must be present for cervical cancer to occur.
• approximately 90% of HPV infections clear on their own
within months to a few years and with no sequelae,
although cytology reports in the 2 years following infection
may show a low-grade squamous intraepithelial lesion.
• 5% of HPV infections will result in the development of CIN
grade 2 or 3 lesions (the recognized cervical cancer
precursor) within 3 years of infection. Only 20% of CIN 3
lesions progress to invasive cervical cancer within 5 years,
and only 40% of CIN 3 lesions progress to invasive cervical
cancer with 30 years.

6. • The following factors have been postulated to
influence the development of CIN 3 lesions:
• The type and duration of viral infection, with high-risk
HPV type and persistent infection predicting a higher
risk for progression; low-risk HPV types do not cause
cervical cancer
• Host conditions that compromise immunity (eg, poor
nutritional status, immunocompromise, and HIV
infection)
• Environmental factors (eg, smoking and vitamin
deficiencies)
• Lack of access to routine cytology screening

7. • Genetic susceptibility-Women who have an
affected first-degree biologic relative have a 2-
fold relative risk of developing a cervical tumor
compared with women who have a nonbiologic
first-degree relative with a cervical tumor.
• Genetic changes in several classes of genes have
been linked to cervical cancer. Tumor necrosis
factor (TNF) is involved in initiating the cell
commitment to apoptosis.

8. • HPV & HIV
• HPV-more than 90% of all cervical cancers worldwide are caused by
8 HPV types: 16, 18, 31, 33, 35, 45, 52, and 58. Three types—16, 18,
and 45—cause 94% of cervical adenocarcinomas.
• low-risk types (eg, HPV 6 and 11) are associated with condylomata
and a very small number of low-grade squamous epithelial lesions
(SILs) but are never found in invasive cancer. The high-risk types (eg,
HPV 16) vary in prevalence according to the cervical disease state.
• HIV-HIV infection is known to suppress the already low level of
immune recognition of HPV infection, allowing HPV to cause more
damage than it would in immunocompetent women.
• Cervical cancer is at least 5 times more common in HIV-infected
women, and this increased prevalence has remained essentially
unchanged with the use of highly active antiretroviral therapy.

9. Natural History and Pattern of Spread
• Most cervical carcinomas arise at the junction between the
primarily columnar epithelium of the endocervix and the
squamous epithelium of the ectocervix.
• This junction is a site of continuous metaplastic change, which
is greatest in utero, at puberty, and during first pregnancy, and
declines after menopause.
• The approximately 15-year difference in the mean ages of
women with CIN and women with invasive cervical cancer
indicates a generally slow progression of CIN to invasive
carcinoma.

10. • Once tumor has broken through the basement membrane, it
may penetrate the cervical stroma directly or through vascular
channels
• exophytic growths protruding from the cervix into the vagina
or as endocervical lesions that can cause massive expansion
of the cervix despite a relatively normal-appearing ectocervix.
• tumor may extend superiorly to the lower uterine segment
• inferiorly to the vagina
• laterally to the broad ligaments (where it may cause ureteral
obstruction),
• posterolaterally to the uterosacral ligaments.

11. • extensive bladder involvement is uncommon, occurring in
fewer than 5% of cases.
• Tumor may also extend posteriorly to the rectum, although
rectal mucosal involvement is a rare finding at initial
presentation

12. Histology of cervix
• The endocervical mucosa is about 3 mm thick, lined with a
single layer of columnar mucous cells, and contains
numerous tubular mucous glands which empty viscous
alkaline mucus into the lumen.
• In contrast, the exocervix is covered with nonkeratinized
stratified squamous epithelium,which resembles the
squamous epithelium lining the vaginal.The junction
between these two types of epithlia is called the
squamocolumnar junction.Underlying both types of
epithelium is a tough layer of collagen.
• prepubertal girls, the functional squamocolumnar junction
is present just within the endocervical canal.

13. • Upon entering puberty, due to hormonal influence, and during
pregnancy, the columnar epithelium extends outwards over the
ectocervix as the cervix everts. Hence, this also causes the
squamocolumnar junction to move outwards onto the vaginal
portion of the cervix, where it is exposed to the acidic vaginal
environment.
• The exposed columnar epithelium can undergo physiological
metaplasia and change to tougher metaplastic squamous
epithelium in days or weeks,which when mature is very similar to
the original squamous epithelium.[The new squamocolumnar
junction is therefore internal to the original squamocolumnar
junction, and the zone of unstable epithelium between the two
junctions is called the transformation zone of the cervix. After
menopause, the uterine structures involute and the functional
squamocolumnar junction moves into the endocervical canal

14. Lymphatic Drainage
• The cervix has a rich supply of lymphatics that drain the
mucosal, muscularis, and serosal layers.
• The most important lymphatic collecting trunks exit laterally
from the uterine isthmus in three groups
• The upper branches, which originate in the anterior and
lateral cervix, follow the uterine artery, are sometimes
interrupted by a node as they cross the ureter, and terminate
in the uppermost hypogastric nodes.
• The middle branches drain to deeper hypogastric (obturator)
nodes.

16. • The lowest branches follow a posterior course to the inferior
and superior gluteal, common iliac, presacral, and subaortic
nodes
• Anterior collecting trunks pass between the cervix and
bladder along the superior vesical artery and terminate in the
internal iliac node
• Cervical cancer usually follows a relatively orderly pattern of
metastatic progression.. initially to nodes in the pelvis and
then to para-aortic nodes and distant sites.
• The most frequent sites of distant recurrence are lung,
extrapelvic nodes, liver, and bone.

17. pathology
• Cervical Intraepithelial Neoplasia
• The term cervical intra epithelial neoplasia denotes a
continuum of disorder from mild through moderate to severe
dysplasia and carcinoma in situ.
• the important features of CIN are cellular immaturity, cellular
disorganization, nuclear abnormalities, and increased mitotic
activity.
• CIN 1--mitoses and immature cells are present only in the
lower third of the epithelium
• CIN 2 - - Lesions involving only the lower and middle thirds
• CIN 3-- also involving the upper third

18.  the Bethesda system
• This system defines squamous intraepithelial lesions (SILs) as
including all squamous alterations in the cervical transformation
zone that are induced by HPV…
• Low-grade SILs (LSILs) --these lesions are usually associated with
low-risk HPV types and have a low likelihood of progressing to
invasive cancers
• HSILs are usually associated with high-risk HPV types and have a
higher likelihood of progressing to invasive cancer.
• Tadpol cells are seen in invasive cancer
• Koilocytes are seen in young women suffering from HPV
infection,are cells with perinuclear haloin the cytoplasm.they
disapper as dysplasia advances.

19. • Adenocarcinoma In situ
• Adenocarcinoma in situ is diagnosed when normal
endocervical gland cells are replaced by tall, irregular
columnar cells with stratified, hyperchromatic nuclei and
increased mitotic activity but the normal branching pattern of
the endocervical glands is maintained and there is no obvious
stromal invasion.
• About 20% to 50% of women with cervical adenocarcinoma in
situ also have squamous CIN .
• Because adenocarcinoma in situ is frequently multifocal, cone
biopsy margins are unreliable.

20. • Microinvasive Carcinoma
• is defined by International Federation of Gynecology and
Obstetrics (FIGO) as “invasive carcinoma which can be
diagnosed only by microscopy, with deepest invasion ≤5 mm
and largest extension <7 mm”
• Thus, this diagnosis can be made only after examination of a
specimen that includes the entire neoplastic lesion and
cervical transformation zone. This requires a cervical cone
biopsy

21. • Lesions that have invaded less than 3 mm (FIGO stage IA1) are
rarely associated with metastases..
• 5% to 10% of tumors that have invaded 3 to 5 mm (FIGO stage
IA2) are associated with positive pelvic lymph nodes..
• importance of LVSI remains somewhat controversial; the risk
of metastatic regional disease appears to be exceedingly low
for any tumor that invades less than 3 mm, even in the
presence of LVSI.

22. • Invasive Squamous Cell Carcinoma
• Between 80% and 90% of cervical carcinomas are squamous cell
carcinomas
• large cell keratinizing, large cell nonkeratinizing, or small cell
carcinomas, these designations do not correlate well with prognosis
• Papillary variants of squamous carcinoma may be well
differentiated or very poorly differentiated
• Verrucous carcinoma is a very rare warty-appearing variant of
squamous carcinoma
• Sarcomatoid squamous carcinoma is another very rare variant,
demonstrating areas of spindle-cell carcinomatous tumor confluent
with poorly differentiated squamous cell carcinoma;
immunohistochemistry demonstrates expression of cytokeratin as
well as vimentin.

23. • Adenocarcinoma
• Invasive adenocarcinoma may be pure or mixed with squamous cell
carcinoma (adenosquamous carcinoma).
• 80% of cervical adenocarcinomas are endocervical-type
adenocarcinomas --are frequently referred to as mucinous
• Minimal-deviation adenocarcinoma (adenoma malignum) –
extremely well-differentiated adenocarcinoma that is sometimes
associated with Peutz-Jeghers syndrome
• Glassy cell carcinoma37 is a variant of poorly differentiated
adenosquamous carcinoma
• Adenoid basal carcinoma is a well-differentiated tumor that
histologically resembles basal cell carcinoma of the skin and tends
to have a favorable prognosis.

24. • Adenoid cystic carcinoma consists of basaloid cells in a
cribriform or cylindromatous pattern; metastases are frequent
• Rarely, primary carcinomas of the cervix are composed of
endometrioid, serous, or clear cells; mixtures of these cell
types may be seen, and histologically, some of these tumors
are indistinguishable from those arising elsewhere in the
endometrium or ovary.

25. • Anaplastic Small Cell/Neuroendocrine Carcinoma
• Anaplastic small cell carcinomas resemble oat cell carcinomas
of the lung
• they frequently display neuroendocrine features
• Anaplastic small cell carcinomas behave more aggressively
than poorly differentiated small cell squamous carcinomas
• survival rates of less than 50% even for patients with early
stage I disease..

26. • Other Rare Neoplasms
• endometrioid histology suggests endometrial origin and
mucinous tumors in young patients are most often of
endocervical origin, both histologic types can arise in either
site
• Metastatic tumors from the colon, breast, or other sites may
involve the cervix secondarily
• Malignant mixed müllerian tumors, adenosarcomas, and
leiomyosarcomas occasionally arise in the cervix but more
often involve it secondarily
• Primary lymphomas and melanomas of the cervix are
extremely rare.

27. • The indian council of medical research reports
an incidence of dysplasia to be
15:1000women cytologicaly
screened.incidence of severe dysplasia
5:1000.
• Risk of dysplasia progressing to frank invasive
carcinoma was 0.5%in mild dysplasia as
compaired to 9.6% of severe dysplasia.

28. Clinical Manifestations
• Preinvasive disease usually detected during routine cervical
cytologic screening
• Early invasive disease may not be associated with any
symptoms and is also usually detected during screening
examinations
• invasive cervical cancer is usually presented with abnormal
vaginal bleeding, often following coitus or vaginal douching.
• associated with a clear or foul-smelling vaginal discharge
• Pelvic pain may result from locoregionally invasive disease or
from coexistent pelvic inflammatory disease.
• Flank pain may be a symptom of hydronephrosis, often
complicated by pyelonephritis.

29. • very advanced tumors may have hematuria or incontinence
from a vesicovaginal fistula caused by direct extension of
tumor to the bladder.

30. Diagnosis
• The long preinvasive stage of cervical cancer, the relatively
high prevalence of the disease in unscreened populations,
and the sensitivity of cytologic screening make cervical
carcinoma an ideal target for cancer screening.
• American College of Obstetrics and Gynecology --guidelines
for cervical cancer screening
 screening is recommended every 2 years to begin at age 21
years
 After age 30 years, the screening interval can be extended to
3 years for women who have no history of CIN 2 or CIN 3, who
are not HIV-infected or otherwise immunocompromised, and
who were not exposed to diethylstilbestrol (DES) in utero.

31.  Women who have had a total hysterectomy for benign
conditions may discontinue routine screening
 It is also reasonable to discontinue screening for women older
than 65 to 70 years who have three or more consecutive
negative studies and have had no abnormal test results in the
past 10 years
 Women previously treated for high-grade CIN or for cancer
should continue to have annual screening for at least 20 years
and periodic screening indefinitely
 Annual gynecologic examination might still be appropriate
even if cytologic screening is not performed.

32. Pap smear[Papanicolaou Testing]
• For many years, the Pap test has been the standard method
for cervical cancer screening.
• Screening programme has proved successful in reducing the
incidence of invasive cancer by 80% and mortality by 60% in
developed countries.
• Accurate calculation of false-negative rates for the Pap test is
difficult; estimates range from less than 5% to 20% or more
• False-negative tests mostly result from sampling error, which
can be reduced by ensuring that adequate material is taken
from both the endocervical canal and the ectocervix. Smears
without endocervical or metaplastic cells should be repeated

35. • Most United States gynecologists currently prefer newer liquid-
based screening methods to conventional Pap tests.
• Here the plastic spatula is placed in liquid fixative witch removes
blood,mucus,inflammatory cells.
• Suspended cells gently sucked onto filter membraneand filtre is
pressed onto glass slideto form a thin monolayer,then it is stained
for cytology and liquid is used to test HPV infection.
• a recent meta-analysis of available data concluded that “liquid-
based cervical cytology is neither more sensitive nor more specific
for detection of high-grade CIN compared with the conventional
Pap.
• Liquid-based tests are more costly but have the potential advantage
that additional studies, such as HPV typing, can be performed on
the fluid remaining after cytologic examination.

36. • Human Papillomavirus Testing
• approved by the FDA in 2003 as a new approach for cervical
cancer.
• This test is useful for interpreting equivocal results from a Pap
test.
• If a woman has a Pap test result showing ASCUS but a
subsequent HPV test is negative, she can be rescreened with
Pap testing in 3 years;
• if the HPV test is positive, then additional workup with a
colposcopy is indicated.
• Combined HPV screening and pap smear yields 96%sensitivity
as compared to only 60-70%with pap smear alone.

37. VIA(Visual inspection of acetowhite
area)
• Where no facilities available for pap screening
• VIA is able to select abnormal area on cervix by applying 5%
of acetic acid which dehydrates abnormal area containing
increased nuclear material and protein which turn
acetowhite.normal cell containing glycogen remain normal.

38. VILI(visual inspection of Lugol’s iodine)
• Normal cell contain glycogen take up iodine
and turn mahogany brown,abnormal area
remain unstained.
• The dull white plaques with faint borders are
considered LSIL and those with sharp borders
and thick plaques contain HSIL.

40. Colposcopy
• Colposcopy is done
• when abnormal findings on cytologic examination
• who do not have a gross cervical lesion must be evaluated
with colposcopy and directed biopsies.
• To study extend of abnormal lesion
• Conservative surgery under colposcopic guidence
• Following application of a 3% acetic-acid solution, the cervix is
examined under 10- to 15-fold magnification with a bright,
filtered light that enhances the acetowhitening and vascular
patterns characteristic of dysplasia or carcinoma.

41. • Abnormal area are acetowhite area,mosaics,punctuation and
abnormal vessels.
• Colposcopic study is challanging in post menapausal because
of narrow vagina,senile vaginitis,squamocolumnar junction
not visible,atropic cervix flushed with vagina.
• Oestrogen cream for 7-10days and 400mcg of misoprostol 3-
4hours before colposcopy.
• In patients with a high-grade Pap smear finding, if no
abnormalities are found on colposcopic examination or if the
entire squamocolumnar junction cannot be visualized, an
additional endocervical sample should be collected.

43. Cervical cone biopsy
• Cervical cone biopsy is used to diagnose occult endocervical
lesions and is an essential step in the diagnosis and
management of microinvasive carcinoma of the cervix
• Cervical cone biopsy yields an accurate diagnosis and
decreases the incidence of inappropriate therapy when
 the squamocolumnar junction is poorly visualized on
colposcopy and a high-grade lesion is suspected,
 high-grade dysplastic epithelium extends into the
endocervical canal,

45.  the cytologic findings suggest high-grade dysplasia or
carcinoma in situ,
 a microinvasive carcinoma is found on directed biopsy,
 endocervical curettage specimens show high-grade CIN
 the cytologic findings are suggestive of adenocarcinoma in
situ.

46. • Descending pyelography,Cystoscopy &
proctoscopy
• PET-detects tissue biochemical changes and
para-aortic node involvement.

47. staging
• Staging of cervical carcinoma is done clinically using
International Federation of Obstetrics and Gynecology (FIGO)
guidelines. It is based on physical examination findings and
also includes results of biopsy, endoscopy and conventional
radiological tests like chest radiograph, intravenous urography
and barium enema.
• FIGO staging system does not consider CT and MRI
mandatory; however, use of these modalities are encouraged
• Stage 0-cervical intraepithelial neoplasia or preinvasive
cervical cancer

48. Stage 1 disease
• Stage 1A,microinvasive
• Stage 1A1 = <3mm
depth of invasion and
<7mm wide
• Stage 1A2 = 3-5mm
depth of invasion and
<7mm wide

49. Stage 1 disease
• Stage 1B = any tumour
which is visible
• Stage 1B1 = <4cm
• Stage 1B2 = >4cm
• Confined to cervix

50. Stage 2 disease
• Stage 2 = invades
beyond uterus, but not
to pelvic sidewall or
lower 1/3 of vagina
• Stage 2A – spread into
the top of the vagina
without parametrial
involvement
• 2A1 = <4cm
• 2A2 = >4cm

51. Stage 2 disease
• Stage 2B – spread into
parametrium

52. Stage 3 disease
• Tumour extends to
pelvic sidewall and/or
involves lower 1/3 of
vagina and/or causes
hydronephrosis
• Stage 3A – Cancer has
spread to lower 1/3 of
vagina, but not to pelvic
sidewall

53. Stage 3 disease
• Stage 3B disease
• Spread to pelvic
sidewall and / or
hydronephrosis

54. Stage 4
• Carcinoma has
extended beyond true
pelvis or has involved
mucosa of bladder or
rectum
• Stage 4a – spread of
growth to adjacent
organ

55. Stage 4 disease
• Stage 4B – spread to
distant organs