What Is the Incidence, Morbidity, and Mortality of HPV-Associated Anal Dysplasia?

Cervical cancer serves as a biologic and an epidemiologic model for anal carcinoma and its precursors. The current incidence of cervical cancer in the United States is approximately 8 cases per 100,000 people. The incidence of anal cancer in men who had sex with men (MSM) prior to the HIV epidemic was 35 per 100,000—an incidence rate similar to that of cervical cancer before routine Pap testing was implemented for the latter (Daling et al, N Engl J Med, 1987). The rate of anal cancer in HIVinfected MSM is approximately twice that in HIV-seronegative MSM (Goedert et al, Lancet, 1998). Cervical and anal cancers have similar histologies, with both frequently arising in the squamocolumnar junction (transformation zone) and both being strongly associated with oncogenic strains of HPV. High-grade squamous intraepithelial lesions (HSIL) are a proven precursor to cervical cancer and are strongly suspected to be a precursor to anal cancer. HPV types include lowrisk types (6 and 11) associated with low-grade squamous intraepithelial lesions (LSIL) and condyloma, intermediate-risk types (31, 33, 35, 45, 51, 52, and 56), and the high-risk types (16 and 18) that are found in approximately two-thirds of cases of invasive cervical cancer. The newly revised Bethesda System of cervical cytologic classification (Solomon et al, JAMA, 2002) also applies to anal intraepithelial neoplasia. In this system, atypical squamous cells (ASC) are classified as “of undertermined significance” (ASCUS) or as “cannot exclude HSIL” (ASC-H). Squamous intraepithelial lesions are graded as LSIL, HSIL, or squamous cell carcinoma. LSIL indicates mild dysplasia (HPV cellular changes) and is equivalent to the cervical intraepithelial neoplasia (CIN) 1 category in the World Health Organization (WHO) histopathologic classification system. HSIL is categorized as either moderate dysplasia, equivalent to CIN 2 in the WHO system, or severe dysplasia, equivalent to CIN 3. The distinction between severe dysplasia and carcinoma in situ, also CIN 3, is very narrow, and the same lesion might be judged as severe dysplasia by one pathologist and carcinoma in situ by another. Cytologically, ASCUS is characterized by features of both LSIL and HSIL with the features being diagnostic of neither. LSIL is characterized by relatively little basal cell proliferation and atypia; the effects of HPV are observed as “koilocytes,” featuring an irregular enlarged nucleus with a clear halo. Most LSILs spontaneously regress. HSIL is characterized by increasingly severe atypia, abnormal mitotic activity in the superficial layers, and immature basaloid cells. Under the Bethesda System, it is recommended that patients with ASCUS findings on Pap testing undergo HPV testing. HPV-positive patients should undergo colposcopy or repeat Pap testing at 6 and 12 months, and HPV-negative patients should have Perspective Screening for Anal Dysplasia Associated with Human Papillomavirus