Background:  The incidence of anal cancer and its precursor squamous intraepithelial lesions (SIL) are increasing in men who have sex with men (MSM). Incidence of SIL and risk factors for its development in HIV-infected individuals, including heterosexual men and women, as well as MSM, have not been extensively investigated. 

Methods:  The SUN Study is an ongoing prospective cohort study of HIV-infected outpatients seen at clinics in Denver, Minneapolis, Providence, and St. Louis. At baseline, and annually thereafter, all patients complete a behavioral risk questionnaire and providers collect, among other specimens, separate Dacron® anorectal swabs for cytologic examination as well as human papilloma virus (HPV) detection and genotyping using the Roche Linear Assay.

Results:  Complete data at both the baseline and 1-year follow-up visits were available for 371 participants. At baseline, 100 patients were diagnosed with anal low-SIL and 28 with high-SIL; these patients were excluded from this analysis. Of the remaining 243 patients with negative anal cytology or atypical squamous cells, 76% were male and 86% had HPV detected. At 1 year, the median age was 42 years, 94% were receiving HAART, 57% had CD4 cells counts (CD4) ≥500 cells/mm³ (median 529.5 cells/mm³) and 79% had undetectable viral loads. Anal cytologic results at 1 year were: negative for 190 (78%), atypical squamous cells for 23 (9%), low-SIL for 25 (10%), and high-SIL for 5 (2%). Univariate analysis indicated that the following factors were associated with incident SIL (p <0.05):  at least 1 high-risk HPV type detected at each visit, a detectable HIV viral load at each visit, current cigarette smoking, non-adherence (defined as missing ≥1 ART dose in a 3-day period) and use of >1 illicit drug (other than marijuana) in the last 30 days. In multivariate analysis, detection of a high-risk HPV type at each visit (OR 10.4, 95%CI 1.3 to 81, p = 0.026), detectable viral load at each visit (OR 3.8, 95%CI 1.3 to 11, p = 0.015) and illicit drug use (OR 6.4, 95%CI 1.0 to 40, p = 0.047) remained associated.

Conclusions:  In this large cohort of generally healthy, HIV-infected men and women, the incidence of anal SIL at 1 year was 12%. Notably, CD4 level and high-risk sexual behaviors (e.g., unprotected anal sex, multiple partners) in the previous year were not associated with incident SIL. Clinicians may wish to consider anal cytology and HPV screening in HIV-infected patients, particularly if they are found repeatedly to have detectable HIV viral loads.