Anal squamous intraepithelial lesions: relation to HIV and human papillomavirus infection

Studies from the era prior to the introduction of highly active antiretroviral therapy (HAART) have shown that the prevalence of anal infection with human papillomavirus (HPV) and anal squamous intraepithelial lesions (ASIL) were high among HIV-positive homosexual men, and to a lesser extent, among HIV-negative homosexual men. The data also show that the incidence of high-grade ASIL (HSIL), the putative invasive cancer precursor lesion, was high in these groups. Early data suggest that at least 75% of those with HSIL lesions do not regress while receiving HAART. Given that progression of HSIL to invasive cancer may require several years, lengthened survival associated with HAART may paradoxically lead to an increased risk of anal cancer. The potential to prevent anal cancer through detection and treatment of anal HSIL suggests a need to screen high-risk individuals with anal cytology, similar to cervical cytology screening to prevent cervical cancer. Cost-effectiveness analyses suggest that anal screening programs may be cost-effective in HIV-positive men. However, barriers to implementation of screening include inadequate numbers of clinicians skilled in diagnosis and treatment of HSIL and lack of medical alternatives to surgical excision. Recent progress in understanding the pathogenesis of ASIL in HIV-positive men points to a role for decreased cell-mediated immunity to HPV antigens as well as the effects of the HIV-1 tat protein in modulating the biology of HPV-infected keratinocytes.