CERVICAL INTRAEPITHELIAL
NEOPLASIA
and
CERVICAL CANCER
OUTLINE
Introduction
Transformation zone of the cervix
Etiology
HPV
Pathogenesis
Risk factors
Cervical intraepithelial neoplasia
Cervical cancer
2
Introduction
• The 2nd most common cause of cancer-
related morbidity and mortality among
women in developing countries
• The average age at diagnosis is 51 years
• It has a long preinvasive state, cervical
cytology screening programs are currently
available & the treatment of preinvasive
lesions is effective
• More than 95% of patients with early
cancer of the cervix can be cured
Transformation zone of the cervix
• Histology of Cervix:
– Endocervix: columnar epithelium
– Ectocervix: stratified squamous epithelium
• The point at which they meet is called
squamocolumnar junction (SCJ)
• SCJ is a dynamic point that it changes In
response to puberty, pregnancy,
menopause and hormonal stimulation.
• Transformation zone is the area from the
original SCJ to physiologically active SCJ. 4
Etiology
• Human papillomavirus (HPV) infection-
80% of all CIN lesions and in 99.7% of all
invasive cervical cancers
HPV
• More than 100 HPV types, half of which
infect the anogenital epithelium.
• Low-risk HPV types (eg, types 6, 11, 42,
43, and 44) => condylomata and low-
grade lesions (CIN I)
• High-risk HPV (such as types 16, 18, 31,
33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and
82) => high-grade lesions (CIN II and CIN
III) and invasive cancer
Pathogenesis
• HPV is epitheliotropic
a) Asymptomatic latent infection
b) Active infection in which HPV undergoes
vegetative replication but not integration into
the genome (eg, leading to condyloma or
CIN I)
c) Neoplastic transformation following
integration of oncogenic HPV DNA into the
human genome
• upregulation of the viral oncogenes E6
and E7
• These oncoproteins interfere with cell-
cycle control in the human host cell.
• E6 and E7 have the ability to complex with
the tumor suppressor genes p53 and Rb,
respectively.
• The disabling of these two major tumor
suppressor genes is thought to be central
to host cell immortalization and
transformation induced by HPV.
• More than 90% of immunocompetent
women will have a spontaneous resolution
of their HPV infection over a 2-year period
• only approximately 5% will have
cytologically detectable CIN..
• The vast majority of women infected with
HPV do not develop CIN or cervical cancer.
This suggests that infection with HPV
alone is insufficient for the development of
CIN or cervical cancer and underscores the
importance of other cofactors, such as
Risk factors
• Multiple sexual partners
• Early onset of sexual activity
• High-risk sexual partner
• Multiparity
• History of STDs
• Cigarette smoking
• Human immunodeficiency virus (HIV)
• Acquired immune deficiency syndrome (AIDS)
• Other forms of immunosuppression
• Long-term oral contraceptive pill
Cervical Intraepithelial Neoplasia
• Cervical intraepithelial neoplasia (CIN)
means disordered growth and
development of the epithelial lining of the
cervix.
• Mild dysplasia or CIN I=> lower 1/3 of the
epithelial lining.
• Moderate dysplasia or CIN II=> lower 2/3
of the epithelial lining.
• Severe dysplasia or CIN III => more than
2/3 of the epithelial thickness with
Symptoms and Signs
• There are usually no symptoms or signs of
CIN
Diagnosis
o Pap smears
o Visual inspection of the cervix
o Colposcopy
o HPV testing
o Staining with Lugol's solution (Schiller
test)
o Colposcopy directed biopsy
o Endocervical curettage
o Diagnostic conization
Bethesda system
• Atypical Squamous cells of Undetermined
Significance (ASCUS)
• Atypical Squamous cells where high-
grade lesions must be excluded (ASC-H).
• Low-grade Squamous Intraepithelial
Lesions (LSIL) include
- CIN 1 (mild dysplasia)
- Changes of HPV, termed Koilocytotic
atypia
• High-grade Squamous Intraepithelial
Lesion (HSIL) include
- CIN 2 and CIN 3 (moderate dysplasia,
screening
Screening should be initiated within 3 years
of the onset of sexual activity or by age 21
years.
Women over the age of 30 with low-risk
factors and three consecutive negative
annual Pap tests can be screened every 2 to
3 years.
Women over the age of 70 with three or
more normal Pap tests in a row in the
previous decade may consider
discontinuation of Pap testing.
Women who have had a total abdominal
hysterectomy (with removal of the cervix) 16
Treatment
• Two ablative techniques cryotherapy and
laser ablation
• Three excisional procedures cold knife
conization, laser cone excision, and LEEP.
• Evidence from controlled trials show that
these techniques are of equal efficacy,
averaging 80–90% success rates in the
treatment of CIN.
Cancer of the Cervix
• The major epidemiologic risk factors for
cervical cancer are the same as those for
CIN
TYPES
squamous cell carcinoma - 70–75%
Adenocarcinomas - (20-25%)
Adenosquamous carcinomas (3–5%)
Sarcomas, neuroendocrine tumors,
melanoma, and primary cervical
lymphoma also occur, but rarely
Direct extension from endometrium,
rectum, and bladder.
Lymphatic or vascular metastases
endometrial, ovarian, gastric, breast,
Clinical Manifestation
• Abnormal vaginal bleeding is the most
common symptom and may take the form
of a blood-stained leukorrheal discharge,
scant spotting, or frank bleeding.
• A history of postcoital bleeding
• Pelvic pain, often unilateral and radiating
to the hip or thigh, is a manifestation of
advanced disease, as is the involuntary
loss of urine or feces through the vagina, a
sign of fistula formation.
• Weakness, weight loss, and anemia are
Investigations
• Biopsy
• Conization
• Radiologic Findings
Clinical Staging
• The classification adopted by FIGO is the most
widely used staging system.
• Cervical cancer is staged by clinical examination,
and evaluation of the bladder, ureters, and rectum.
• If the lesion is clearly confined to the cervix by
office examination, only chest radiography and
evaluation of the ureters by IVP or CT scan with
intravenous contrast is necessary to assign the
stage. If it is not possible to evaluate the extent of
local disease in the office, examination under
anesthesia with cystoscopy and proctoscopy may
be necessary.
• Although CT scan, MRI, lymphangiography, and
PET scan may offer information helpful for
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Treatment
• Radical hysterectomy and pelvic
lymphadenectomy
• Radiation with concomitant chemotherapy
• combination
24
Five-year survival rates
• with radiotherapy alone are comparable
for survival with surgery alone for stages
IA and IIA disease= 75-100%
• For advanced-stage disease localized to
the pelvis= 50% to 80%.
• For metastatic disease out of the pelvis,
survival is less than 15%.
25
prevention
• HPV vaccines
• Screening
• Avoid multiple sexual partner
• Stop smoking
• ART drugs
26
References
• Current Diagnosis & Treatment Obstetrics &
Gynecology
• Williams' Gynecology
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Thank you
