Epidemiology and Risk Factors Invasive cancer of the cervix is considered a preventable disease because It has a long preinvasive state, cervical cytology screening programs are currently available, and the treatment of preinvasive lesions is effectiveIncidence © cervical cancer - second most common and the fifth most deadly cancer in women © affects about 16 per 100,000 women per year and kills about 9 per 100,000 per year © approximately 80% of cervical cancers occur in developing countries0 Philippine Cancer Facts and Estimates © Incidence of cervical CA remained stable from 1980-2005 o Annual age-standardized incidence rate of 22.5 cases per 100,000 women 0 2005 - 7,277 new cases of cervical CA, with 3807 reported deaths o Overall 5-year survival rate - 44% o Mortality rate - 1/10,000 women0 2/3 of cervical CA in the Philippines are diagnosed in an advance stage, and mortality is high o advance clinical stage at presentation o Significant proportion of patients do not receive or complete prescribed courses of treatmentRisk Factors co HPV Infection - HPV 16 and 18 ° The presence of HPV-DNA in cervical neoplasia is the first necessary cause of a human CA identified e High Grade ( invasive cancer) Co HPV type 16, 18, 45, 56 o Intermediate Grade (CIN II / Ill) HPV type 31, 33, 35, 51, 52 Low Grade (Condyloma a. / CIN!) HPV type 6, 11. 40, 41, 42 So 8o Parity of > 7 - 4x increase © High parity may increase the risk of cervical CA because it maintains the transformation zone on the ectocervix for many years facilitating the direct exposure to HPV © Hormonal changes induced by pregnancy may also modulate the immune responseo Longterm use of OCP - 4x increase with HPV Infection © Increased significantly with a use of 5-9 years and with a use of 210 years o Hormone related mechanisms may influence the progression from premalignant to malignant cervical lesions by promoting integration of HPV DNA into the host genome, which results in the deregulation of E6 and E7 expression o Associated with Adenocarcinomao Smoking - the risk of SCCA increases in current smokers with the number of cigarettes smoked per day and with younger age at starting smoking © Nicotine and tobacco-specific carcinogens have been detected in the cervical mucus of smokers o Chemical tobacco-related carcinogens may exert a direct mitogenic effect causing DNA damage o No association between smoking and adenocarcinoma9S CO- infection with HPV and C. trachomatis or HSC-2 Women with HIV (+) infection Increased lifetime number of sexual partners o Risk of invasive cell CA increased Early age at first intercourse - < 14 y/o Early age at first full term pregnancy (< 17 y/0) 0 Risk of both invasive and CIN 3/CISo Male circumcision - reduced risk of penile HPV infection o Risk of developing invasive cervical CA is 3- 10x greater in women who have not been screened © Low socio economic statusCERVICAL CYTOLOGY TESTING o The technique requires that the cervix be visualized after placement of a speculuminto the vagina. o The portio of the cervix is then scraped using a “broom” or the combination of a plastic spatula and endocervical brusho ACOG Pap testing o Pap testing for all women beginning at age 21o Pap test and HPV DNA testing o most effective testing after age 30 © If both tests are negative, the risk of HSIL during the next 3 to 5 years is extremely low. © if one test is positive and one negative, the Clinician should repeat both tests in 6 to 12 months o Annual testing with cytology alone is acceptable although not necessary for most women.o Testing after TAH - history of an HSIL, are immunocompromised, or were exposed in utero to diethylstilbestrol o Pap testing - can be stopped 65-70 years oldCERVICAL CYTOLOGY REPORTING: THE BETHESDA SYSTEM o Adequacy of sample* © Satisfactory © Unsatisfactory o Squamous cell abnormalities © Atypical squamous cells (ASC) o ASC of undetermined significance o ASC cannot exclude high-grade lesion o Low-grade squamous intraepithelial lesion o High-grade squamous intraepithelial lesion o Squamous cell carcinomao Glandular cell abnormalities o Atypical glandular cells, specify site of origin, if possible o Atypical glandular cells, favor neoplastic o Adenocarcinoma in situ o Adenocarcinoma o Other cancers (e.g., lymphoma, metastatic, sarcoma)First Step in Evaluation of a Woman with an Abnormal Cervical Cytology Report o Squamous lesions o ASC-US: HPV DNA testing for HR types; repeat Pap test in 6 months; colposcopy (all three options acceptable) o ASC-H: Colposcopy © LSIL: Colposcopy or HPV DNA testing o HSIL: Colposcopy o Glandular lesions: All reports require colposcopy and further evaluation if negativeNATURAL HISTORY OF CERVICAL INTRAEPITHELIAL NEOPLASIA o CIN is graded as 1, 2, or 3 depending on the percentage of the thickness of the epithelium that demonstrates cells with nuclear atypiao CIN1-mild dysplasia, result from an infection with HPV © In most cases, these lesions disappear spontaneously, often within weeks to monthso CIN 2- When the process of cell transformation involves one half to two thirds of the thickness of the epithelium © process still remains reversible at this stage, with approximately 40% disappearing spontaneously without treatment,o CIN 3- When the neoplastic process involves the full or almost full thickness of the epithelium o encompasses what was once called severe dysplasia and carcinoma in situ o Requires TxTZ - is the area that lies between normal columnar epithelium and mature squamous epithelium. o TZis important because most cases of squamous neoplasia of the cervix begin in this anatomic area, Probably because it is an area of rapid cell turnoverEVALUATION OF ABNORMAL CYTOLOGY: COLPOSCOPY 0 microinvasive carcinoma of the anterior lip of the cervix 0 (+) abnormal vessels ~ (+) bleeding0 squamous metaplasia - When the vagina becomes acidic at the time of menarche, this single columnar cell layer is gradually replaced by squamous epithelium o Squamous epithelium is much more resistant to the low pH of the mature vagina~0 Colposcopy during pregnancy is difficult.* o Invasive cancer must bee ruled out o Colposcopy plays a key role in a pregnant woman with an abnormal Pap test result. o If there is no evidence of invasion, further evaluation can be postponed until 6 to 12 weeks after delivery o **o The only indication for an excisional procedure in pregnancy @ possible presence of invasive disease © aconization procedure under anesthesia is recommended o If CIN was identified during pregnancy, a follow- up colposcopic examination should be scheduled postpartum o However, it should not be attempted until at least 6 weeks have passed. Often, the lesion will have disappeared, even if it was CIN 3.TREATMENT o CIN 1- Treatment ofCIN1 inwomen younger than 21 years is not recommended, unless the lesion persists for more than 24 months © require follow- up to ensure that the lesion regresseso CIN 2 - Approximately 40% of CIN 2 lesions also regress spontaneously o If a lesion progresses to CIN 3, it should be treated.Treatment Methods © The goal of treatment of CIN is to remove the lesion © 1. Ablation (e.g., cryotherapy,thermoablation, CO2 laser ablation) 0 2. excision (e.g., LEEP [also known as large loop excision of the transformation zone, LLETZ] © 3.cold knife conization, © 4.CO2 laser conizationAblative Methods CRYOTHERAPY © outpatient method was the most commonty used treatment After colposcopy and sampling have shown that the lesion is confined to the exocervix. a probe is selected that will cover the entire lesion . The probe ts applied to the a emer cervix and the system (s activated The cervix will freeze quickly. but the probe must remain in place until the ice ball that forms extends to at least 5 mm beyond the edge of the instrument. In most cases. this takes 3 to 4 minutes The refngerant is then tumed off and the probe Is allowed to thaw and separate from the cervixo CO2 LASER ABLATION o When a focused CO2 laser beam is directed at the cervical epithelium, the laser energy is absorbed by the water in the cells. o The water turns to steam and the cell wall disrupts, killing the cell. © The cell protein is largely exploded in a plume of smoke that is drawn out of the vagina by suctiono EXCISIONAL METHODS o LOOP ELECTROSURGICAL EXCISION © LEEP is currently the most common method for the treatmenof CIN 2 and 3. ¢ It involves the of the TZ of the cervix under local anesthesia and can be performed safely and without discomfort in the officeo COLD KNIFE CONIZATION o Under general anesthesia, the cervix would be stained with an iodine-containing solution and all the epithelium that did not stain would be removed. 0 The knife would be angled toward the endocervical canal, thus removing a cone- shaped piece of tissue