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  1. What is the burden of disease?

    1. About 12,900 new cases of cervical cancer and 4100 cervical cancer–related deaths estimated in the United States in 2015

    2. Incidence rates vary by race/ethnicity: 11.1 per 100,000 in Hispanic women; 10 per 100,000 in black women; 7.4/100,000 in white women; 7.3/100,000 in Asian women

    3. Rates are considerably higher in countries where cytologic screening is not widely available; worldwide, cervical cancer is the second most common cancer in women and the most common cause of mortality from gynecologic malignancy.

    4. Women with preinvasive lesions have a 5-year survival of nearly 100%, with a 92% 5-year survival for early-stage invasive cancer; only 13% survive distant disease.

  2. Is it possible to identify a high-risk group that might especially benefit from screening?

    1. 93–100% of squamous cell cervical cancers contain DNA from high-risk human papillomavirus (HPV) strains.

      1. Low- and high-risk subtypes

      2. Cervix especially vulnerable to infection during adolescence when squamous metaplasia is most active.

      3. Most infections cleared by the immune system in 1–2 years without producing neoplastic changes.

        1. 90% of low-risk subtypes resolve over 5 years

        2. 70% of high-risk subtypes resolve

      4. Women older than 30 years with HPV are more likely to have high-grade lesions or cancer than women younger than 30 with HPV.

    2. Early-onset of intercourse (before age 17) and a greater number of lifetime sexual partners (> 2) are risk factors for acquiring HPV.

    3. Cigarette smoking increases risk by 2- to 4-fold.

    4. Immunocompromise and other sexually transmitted infections, such as herpes and HIV, also increase risk.

    5. In utero exposure to diethylstilbestrol and previous treatment for high-grade lesions are also risk factors for cervical cancer.

  3. What is the quality of the screening test?

    1. Interpretation of Pap smears: the Bethesda Classification of Cervical Cytology

      1. Negative for intraepithelial lesion or malignancy

      2. Epithelial cell abnormalities: squamous cells

        1. Atypical squamous cells (ASC)

          1. ASC-US: of undetermined significance

          2. ASC-H: cannot exclude high-grade squamous intraepithelial lesion

        2. Low-grade squamous intraepithelial lesion

          1. Cellular changes consistent with HPV

          2. Same as mild dysplasia, histologic diagnosis of cervical intraepithelial neoplasia (CIN) 1

        3. High-grade squamous intraepithelial lesion

          1. Same as moderate/severe dysplasia, histologic diagnosis of CIN 2, CIN 3, CIS (carcinoma in situ)

          2. Should indicate if invasion suspected

        4. Squamous cell carcinoma

      3. Epithelial cell abnormalities: glandular cells

        1. Atypical (endocervical, endometrial, or glandular)

        2. Atypical, favors neoplastic

        3. Endocervical adenocarcinoma in situ

        4. Adenocarcinoma

    2. Pap smear techniques

      1. Conventional Pap smear: cervical cells are spread on a glass slide and treated with a fixative by the examiner

      2. Liquid-based cytology: cervical cells are suspended in a vial of liquid preservative by the examiner, followed by debris removal and placement onto a slide in the laboratory

    3. HPV testing

      1. A cervical specimen is placed into a transport medium or into the liquid preservative used for the liquid-based cytology Pap smear method.

      2. Specific RNA probes are added that combine with oncogenic DNA, and the DNA-RNA hybrids are detected by antibodies.

    4. Test characteristics of conventional and liquid-based cytology are the same.

      1. Sensitivity for high-grade squamous intraepithelial lesion is ~56%; for low-grade squamous intraepithelial lesion, ~77%.

      2. Specificity for high-grade squamous intraepithelial lesion is ...

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