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Objective: To evaluate the prevalence of anal cytology (ACyt) abnormalities among HIV-infected and HIV-uninfected men who have sex with men (MSM)., Design: Multicenter cohort study of 723 HIV-infected and 788 HIV-uninfected MSM with ACyt, with a second ACyt collected 2 years later. A referral for high-resolution anoscopy was suggested for abnormal ACyt., Methods: ACyt samples were collected using a polyester swab and liquid cytology media and read in a central laboratory., Results: Prevalence of any abnormal ACyt was 25% in HIV-uninfected MSM and increased to 38%, 41%, and 47% among HIV-infected MSM with current CD4 T-cell counts ≥500, 350-499, and <350 cells/mm (P < 0.001), respectively. Anal HPV16 DNA was also more common in HIV-infected than HIV-uninfected MSM (25% versus 16%, P < 0.001). Abnormal baseline ACyt together with prevalent HPV16 DNA detection was present in only 7% of HIV-uninfected MSM compared to 18% of HIV-infected MSM with current CD4 < 350, P < 0.001. Among HIV-infected men, 56% of the men with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions ASCs-US/LSILs and 81% of men with atypical squamous cells cannot exclude high-grade (ASC-H/)/high-grade squamous intraepithelial lesions (HSIL) had lower grade ACyt findings 18-30 months later ("regressed"). However, 19% of untreated HIV-infected men with ASC-H/HSIL cytology maintained that same grade of cytology in their second test approximately 2 years later, and 15% with ASC-US/LSIL "progressed" to ASC-H/HSIL. Abnormal ACyt had high sensitivity (96%) but low specificity (17%) for biopsy-proven HSIL., Conclusions: Prevalence of abnormal ACyt remains elevated in HIV-infected men during the current antiretroviral therapy era.

Objective: Human papillomavirus (HPV) vaccination is routinely recommended in HIV-positive men who have sex with men (MSM) aged ≤ 26 years. Levels of previous HPV exposure in older HIV-positive MSM are assumed to be too high to warrant routine HPV vaccination. However, little is known about the prevalence of and risk factors for neutralizing antibody seropositivity to HPV-16 or HPV-18, a key measure of previous exposure to these types., Methods: Cross-sectional analysis of baseline visit for 296 HIV-positive MSM participating in a prospective cohort study of anal squamous intraepithelial lesions at a university-based research clinic. Participants completed a questionnaire detailing behaviors and medical history. Phlebotomy, anal cytology, HPV DNA testing with quantitation, and high-resolution anoscopy with biopsy were performed. A pseudovirion-based neutralizing antibody assay was used to measure HPV-16 and HPV-18 neutralizing antibodies., Results: One hundred thirty-two of 296 (45%) men were HPV-16 seropositive and 141 of 296 (48%) were HPV-18 seropositive. One hundred seventy-five of 296 (59%) of the men were positive for HPV-16 antibodies or DNA and 167 of 296 (56%) were positive for HPV-18 antibodies or DNA. In multivariable analysis, HPV-16 seropositivity did not correlate with age, years of HIV positivity, CD4 level, or HIV viral load. Significant risk factors included HPV-16 DNA positivity with higher DNA levels (ptrend < 0.001) and higher number of receptive sexual partners in the last year (ptrend = 0.012)., Conclusions: A high proportion of HIV-positive MSM aged >26 years are DNA negative and seronegative to HPV-16 and HPV-18 even when using a sensitive pseudovirion-based neutralizing antibody assay. Prospective studies are needed to determine the clinical- and cost-effectiveness of HPV vaccination in HIV-positive MSM aged >26 years.

Background: Anal intraepithelial neoplasia (AIN) is common in men who have sex with men (MSM) and may be diagnosed by anal cytology screening., Methods: One hundred two MSM with clinician-collected anal cytology and histopathology specimens were assessed from a cohort study of AIN at the University of California at San Francisco. The men were given a cytology self-collection kit with written instructions for use and requested to collect the sample 1 month after the clinic visit., Results: Ninety-one percent of self-collected and 99% of clinician-collected anal cytology samples were adequate for interpretation. The sensitivity of abnormal anal cytology to detect AIN by histology was 68% in self-collected samples and 70% in clinician-collected samples, and the sensitivity to detect AIN 2 or AIN 3 was 71% and 74%, respectively. Cytologic results did not differ by grade between self-collected and clinician-collected samples. Among MSM diagnosed with AIN 2 or 3 by biopsy, 33% of self-collected and 39% of clinician-collected cytology samples were high-grade. The sensitivity of both self-collected and clinician-collected samples to detect AIN 2 or 3 was higher among HIV-positive MSM than among HIV-negative MSM., Conclusions: MSM with biopsy-proven AIN can self-collect anal cytology samples with sensitivity comparable with that of experienced clinicians. This may facilitate screening for AIN.

The effect of highly active antiretroviral therapy (HAART) on the natural history of anal squamous intraepithelial lesions (ASIL)-the likely anal cancer precursor-and anal human papillomavirus (HPV) infection is unknown. ASIL severity and level of anal HPV DNA were evaluated among HIV-positive men who have sex with men (MSM) for at least 6 months before initiation of HAART. The results were compared with those from a 6-month period after initiation of HAART. Anal swabs for cytology and HPV studies were obtained, followed by high-resolution anoscopy and biopsy. Among men whose most severe pre-HAART diagnosis was atypical squamous cells of undetermined significance or low-grade ASIL, 18% (confidence interval [CI], 6-31%, 7 of 38) progressed and 21% (CI, 8-34%, 8 of 38) regressed 6 months after starting HAART. Seventeen percent (CI, 0-38%, 2 of 12) of study subjects who began with a normal diagnosis developed ASIL. Only 4% (CI, 0-10%, 1 of 28) of study subjects with high-grade ASIL regressed to normal. There was no reduction in the proportion of study subjects who tested positive for HPV DNA or HPV DNA levels after HAART initiation. The ASIL and HPV data were similar to those of the pre-HAART comparison period. These results indicate that HAART has little effect on either ASIL or HPV in the first 6 months after HAART initiation.