Studies from the era prior to the introduction of highly active antiretrovi
ral therapy (HAART) have shown that the prevalence of anal infection with h
uman 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 le
sions do not regress while receiving HAART. Given that progression of HSIL
to invasive cancer may require several years, lengthened survival associate
d with HAART may paradoxically lead to an increased risk of anal cancer. Th
e potential to prevent anal cancer through detection and treatment of anal
HSIL suggests a need to screen high-risk individuals with anal cytology, si
milar to cervical cytology screening to prevent cervical cancer. Cost-effec
tiveness analyses suggest that anal screening programs may be cost-effectiv
e in HIV-positive men. However, barriers to implementation of screening inc
lude inadequate numbers of clinicians skilled in diagnosis and treatment of
HSIL and lack of medical alternatives to surgical excision. Recent progres
s 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 e
ffects of the HIV-1 tat protein in modulating the biology of HPV-infected k
eratinocytes.