PROGRESSION OF ANAL SQUAMOUS INTRAEPITHELIAL LESIONS IN HIV-POSITIVE AND HIV-NEGATIVE HOMOSEXUAL/BISEXUAL MEN

Abstract

Background: Men with a history of receptive anal intercourse have been shown to be at increased risk of anal cancer compared to the general population, and HIV+ men may be at particularly high risk. Like cervical cancer, anal cancer may be preceded by precancerous disease known as high-grade squamous intraepithelial lesion(HSIL). Little is known about incidence of anal HSIL and associated risk factors. This study was designed to characterize progression of anal disease and incidence of HSIL in a prospective cohort study of HIV+ and HIV− homosexual/bisexual men. Methods: 346 HIV+ and 262 HIV− men were enrolled at baseline in this study, which included an extensive interview, anal cytology, anoscopy with biopsy of visible disease, anal HPV testing and CD4 measurement. Subjects with no anal disease were followed every 6 to 12 months. Subjects with anal disease defined as atypical squamous cells of undetermined significance or low-grade squamous intracpithelial lesion (LSIL) were assessed every 3 months, with development of HSIL as the endpoint. HPV was sought using the polymerase chain reaction with the HPV L1 consensus primers and probes in a dot-blot format, followed by specific typing for 39 different HPV types. Results: Compared to HIV− subjects, HIV+ subjects had a higher incidence of HSIL within 2 years of followup (RR-2.2, Cl 1.6-3.1). Of the 87 HIV+ men who were normal at baseline, 28 (32%) progressed to LSIL and 17 (20%) progressed to HSIL within 2 years. Of the 137 HIV− men who were normal at baseline, 12 (9%) progressed to LSIL and 11 (8%) progressed to HSIL within 2 years. Of the 55 HIV+ men with LSIL at baseline, 34 (62%) progressed to HSIL and of the 14 HIV− men with LSIL, 5 (36%) progressed to HSIL within 2 years. Defining disease progression as movement from one anal disease state to a higher grade within 2 years, lower CD4 counts among HIV+ subjects were associated with disease progression (p for trend<0.001). Among HIV+ subjects, the RR for anal progression was 1.6 for presence of a single HPV type and 2.0 for multiple types when compared to HIV+ men without HPV infection (p for trend 0.002). Among the HIV− subjects, the RR for anal disease progression was 3.7 for presence of a single HPV type and 5.1 for multiple types when compared to HIV− men without HPV infection(p for trend < 0.0005). Lifestyle risk factors such as smoking, alcohol and recreational drug use, and amount of receptive anal intercourse were not associated with anal disease progression in HIV+ or HIV− men. Conclusions: HIV+ homosexual/bisexual men had a high estimated two-year incidence of HSIL. HIV− men had a lower, but still appreciable incidence of HSIL. The primary risk factors for anal discase progression among HIV+ men included lower CD4 counts and infection with multiple HPV types. Among HIV− men, the primary risk factor was infection with multiple HPV types. Although the progression rate from HSIL to invasive cancer is not known, both HIV+ and HIV− homosexual/bisexual men with HSIL should be considered at risk for developing anal cancer. Supported by grant number R01 CA54053.