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GYNECOLOGY
2.4C PREMALIGNANT & MALIGNANT DISEASES OF THE CERVIX

HISTORY, EPIDEMIOLOGY & INFECTION


Human Papilloma virus infection (HPV) discovered as the true
cause of cervical cancern(worldwide prevalence of HPV in
cervical cancer is 99.7%)
HPV double stranded DNA viruses that replicate within
epithelial cells
More than 120 types affect humans (40 were known to infect the
genital tract/ 13 which were associated with cancer)
Transmitted through sexual activity
Not all women infected with HPV develop cancer

SCREENING
Pap smear reduced incidence of cervical cancer by 50-70%
Pap testing for all women beginning at age 21 annually
HPV DNA test with pap smear (co test) every -5 years
Pap after hysterectomy not necessary except if with history of
HSIL and DES exposure, immunocompromised
Can stop at 65-70 years old
The Bethesda System for Reporting Cervical Cytology
Adequacy of Sample
- Satisfactory
- Unsatisfactory
Squamous cell abnormalities
- Atypical squamous cells (ASCUS, ASC-H)
- Low grade squamous intraepithelial lesion (LSIL)
- High grade squamous intraepithelial lesion (HSIL)
Glandular cell abnormalities
- Atypical glandular cells
- Atypical glandular cells, favor neoplastic
- Adenocarcinoma in situ
- Adenocarcinoma
Others
- Lymphoma, metastatic sarcoma
Squamous cell abnormalities are found in 5-6% of all cytology
samples
- LSIL CIN 1
- HSIL CIN 2 or 3

Cofactors in the development of cervical cancer:


- Smoking
- Immunocompromised state
- OCP use
- early coitus, early age at first delivery, multiparity
HPV causes neoplastic cellular changes when its DNA becomes
integrated into the host cell genome
Inactivation of the tumor suppressor genes p53 and Rb leading
to cell immortalization and rapid cell proliferation
MECHANISM OF ACTION OF HPV

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Gynecology

2.4C PREMALIGNANT & MALIGNANT DISEASES OF THE CERVIX

Evaluation after pap smear


- ASCUS HPV DNA testing, repeat pap or colposcopy
- ASC-H colposcopy
- LSIL colposcopy or HPV DNA testing
- HSIL colposcopy
- Glandular lesions - colposcopy

LEEP

COLPOSCOPY

Cold knife conization

Hysterectomy not recommended


95% success rates
Repeat pap smear after 6-12 months

CERVICAL CANCER
EPIDEMIOLOGY IN THE PI
5th leading cancer for both sexes
1st of the genital tract cancers
2nd cancer among women

Low power binocular microscope magnification 3 -15x


Dilute acetic acid is applied to the cervix
Evaluation of the transformation zone- area of rapid cell turnover
where squamous metaplasia occurs
Punch biopsy done on the lesions

TREATMENT
CIN 1 follow up; treatment is no longer the preferred method;
treatment done if persisted more than 12 months (for <21 yrs old
24 months)
CIN 2 follow up, then treatment as necessary
CIN 3 should be treated
Ablation
- Cryotherapy
- Thermoblation
- Co2 laser ablation
Excision
- LEEP/LLETZ
- Cold knife conization
Cryotherapy

HISTOLOGIC TYPES
Squamous Cell Carcinoma - 80 -85% of the tumors
- Large cell keratinizing or non-keratinizing
- Small cell
- Verrucous
Adenocarcinoma 15 20%
- Typical (endocervical)
- Endometrioid
- Clear Cell
- Adenoid cystic
- Adenoma malignum
Mixed carcinoma
- Adenosquamous
- Glassy cell Carcinoma

SQCC

Adenocarcinoma

CLINICAL FEATURES
Mean age 40-60 years old, median age of 52
Increasing incidence in less than 40 years old
Abnormal bleeding or brownish discharge following intercourse
or between periods
Absence of screening
Late symptoms
- Back pain
- Loss of appetite
- Weight loss
- Bone pain
- Urinary and bowel disturbances
- edema

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Gynecology

2.4C PREMALIGNANT & MALIGNANT DISEASES OF THE CERVIX

RISK FACTORS
Smoking
Multiple sexual partners
Early coitus
Early age at first delivery
Multiparity
OCP use
Absence of screening
Immunocompromised state
DIAGNOSTICS
Diagnosis is made by biopsy
Imaging studies
- Chest X ray
- Transvaginal ultrasound
- Abdominopelvic CT scan/ ultrasound
- KUB - IVP
- Cystoscopy, proctosigmoidoscopy if needed
STAGING
I - Carcinoma is confined to the cervix
- IA microscopic; deepest invasion 5 mm and largest
extension 7 mm
- IB clinically visible lesions greater than IA
IB1 size 4 cm
IB2 size > 4 cm
II Carcinoma invades beyond the uterus but not to the pelvic
wall or to the lower 1/3 of the vagina
- IIA No obvious parametrial involvement
IIA1 size 4 cm
IIA2 - size > 4 cm
- IIB obvious parametrial involvement
III tumor extends to the pelvic wall and/or involves the lower
third of the vagina and/or causes hydronephrosis or nonfunctioning kidney
- IIIA Tumor involves the lower third of the vagina without
involvement of the pelvic wall
- IIIB Extension to the pelvic wall and/or hydronephrosis or a
nonfunctioning kidney
IV carcinoma has etended beyong the pelvis or has involved the
mucosa of the bladder or rectum
- IVA adjacent pelvic organs
- IVB distant organs

NATURAL HISTORY & SPREAD


Tumor may be ulcerated
Exophytic cauliflower like appearance
Endophytic start from endocervical location (barrel shaped)

Spread
- Direct extension
- Lymphatic regional pelvic nodes, paraaortic, supraclavicular
- Hematogenous - lung, liver, less frequently in bone

PROGNOSTIC FACTORS
FIGO stage most important determinant of prognosis
Others:
- Tumor size
- Lymph node involvement
- Adenocarcinoma histology in some studies demonstrated to
have higher relapse rate than squamous cancers
TREATMENT
Stage IA (microinvasive cancers)
- IA1 - Cone biopsy, simple trachelectomy or simple
hysterectomy
- IA2 modified radical hysterectomy or trachelectomy and
pelvic lymphadenectomy
Stage IB and early stage IIA Radical hysterectomy with lymph
node disssection with or without adjuvant concurrent
chemoradiation
In younger patients, surgery can preserve ovarian function
Stage IIB IV Concurrent Cisplatin chemotherapy and pelvic
external beam/ EFRT followed by brachytherapy
Other options: neoadjuvant chemotherapy when access to
radiotherapy is poor or there are delays in delivering
radiotherapy
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