Harvard-MIT Division of Health Sciences and Technology HST.071: Human Reproductive Biology Course Director: Professor Henry Klapholz HST 071IN SUMMARY CERVICAL NEOPLASIA AND PAP SMEAR CERVICAL NEOPLASIA Appearance of Cervix • The normal appearance of the cervix -central cervical os and the smooth, glistening epithelial surface • The normal appearance of the cervical epithelium -orderly maturation of the basal cells along the basement membrane • demarcation between the normal cervical mucosa -dysplastic epithelium • koilocytotic change -human papillomavirus infection -vacuolization of epithelial cells. • Cytologic features of dysplasia • Increased nuclear/cytoplasmic ratio • Darker and more irregular nuclei • Large amount of cytoplasm and small pyknotic nuclei • Fungating, exophytic tumor -typical for invasive squamous cell carcinoma. • Nests of tumor cells have broken through the basement membrane -invade underlying stroma What is a Pap Smear ? • Exfoliated cells can be obtained from various body sites • Many cells and tissues -constant process of maturation/death/regeneration • Cells that die slough off or exfoliate • Proliferation and maturation leads ultimately to exfoliation of cells • Collect exfoliated cells - primarily from epithelial surfaces • Mechanically enhance the exfoliation process - spatulas or brushes • Single cells or small tissue fragments Infections Detected by Pap Smear • Chlamydia • Gardnerella vaginalis • Trichomonas vaginalis • Neisseria gonorrhea • Group B Streptococcus • Candida albicans • Herpes simplex • Treponema pallidum (syphilis) • Human papillomavirus Cervical Intraepithelial Neoplasia (CIN) – Risk factors • Sexual intercourse at a young age • Multiple sexual partners • Intercourse with a high risk male • History of HPV infection INTERPRETATION •ASC-US (undetermined significance) •ASC-H (cannot exclude HSIL) •ALL ASC is suggestive of SIL •Some cases of ASC-US may represent CIN-2 or 3 PURPOSE OF THE PAP SMEAR •Detection of occult pathologic abnormalities of the uterine cervix in asymptomatic women •Detection of recurrence of known pathologic abnormalities of the uterine cervix •Evaluation of a suspected hormonal abnormalityIN SUMMARY HST 071 CERVICAL NEOPLASIA AND PAP SMEAR •Monitoring of hormonal therapy Role of HPV • World-wide, genital warts (condylomata acuminata) is one of the most common sexually transmitted diseases • Genital warts is one of the most common new diagnoses made at genito-urinary clinics • Highest rates occur in men and women aged 18-28 years • The highest rates of genital HPV infection are consistently found in sexually active women <25 years of age • In developed countries, genital HPV infection has increased steadily since the 1950s • About 1% of all sexually active adults (15-49 years of age) either have had or have genital warts • Only a very small percentage of those infected with the HPV virus actually develop genital warts. • An overall estimate is that 15% of this population (at least 20 million adults) is infected • The prevalence of genital warts is higher in certain populations, especially those attending STD clinics. • Global prevalence of condylomata is between 1-2% of the sexually active population 15-49 years of age. Risk Factors Associated with Acquiring HPV Infection • The risk of acquiring HPV infection increases with increasing numbers of partners, increasing frequency of intercourse, and having sex with infected partners • Studies looking at the use of condoms have been inconclusive • Similar rates of HPV infection are found in pregnant and non-pregnant women • Highest rates of genital HPV infection are consistently found in sexually active women <25 years of age • Initiation of sexual intercourse at an early age • Infection with other STDs • Increased frequency of sexual intercourse per week • Oral contraceptives may slow disease progression in women already infected with HPV • Correlation between smoking and malignant manifestations of HPV disease • Deficiency of cell-mediated immunity will create a risk factor transplant patients • diabetes mellitus • drugs such as steroids and chemotherapy • cancer • More than 150 HPV types have been identified • More than 90% of genital wart lesions examined are associated with HPV types 6 and 11 • The risk of genital tract cancer from HPV types 6, 11 or 42 -44 is considered low or negligible • HPV types 16 and 18 have been strongly implicated in cervical and other anogenital cancers • 99.8% of patients who develop CIN are infected with the HPV virus What are the signs of cervical cancer? • Early stages of cervical cancer usually do not have any symptoms. • Abnormal bleeding • Bleeding after sexual intercourse -in between periods • Heavier/longer lasting menstrual bleeding • Bleeding after menopause • Abnormal vaginal discharge (may be foul smelling) • Pelvic or back pain • Pain on urination • Blood in the stool or urine • Non-specific, and could represent a variety of different conditionsIN SUMMARY HST 071 CERVICAL NEOPLASIA AND PAP SMEAR Staging of Cervical Cancer • Stage IA -microscopic cancer confined to the uterus • Stage IB -cancer visible by the naked eye confined to the uterus • Stage II -cervical cancer invading beyond the uterus but not to the pelvic wall or lower 1/3 of the vagina • Stage III -cervical cancer invading to the pelvic wall and/or lower 1/3 of the vagina and/or causing a non-functioning kidney • Stage IVA -cervical cancer that invades the bladder or rectum, or extends beyond the pelvis • Stage IVB -distant metastases Type of Cancers • Cervical intraepithelial neoplasia (CIN). This is a term used to describe abnormal changes on the surface of the cervix after biopsy. CIN — along with a number (1, 2 or 3) — describes how much of the lining of the cervix contains an abnormal growth of cells. Another term for this condition is dysplasia. • Carcinoma in situ (CIS). This cancer involves cells on the surface of the cervix that haven't spread into deeper tissues. Treatment to remove the cancer is necessary and highly successful. • Cervical cancer. Abnormal cells will eventually invade deeper tissues and may spread into blood vessels and the lymphatic system, where they can be carried to distant
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