Abnormal Anal Cytology Found in Half of HIV-Positive Gay Men

Daniel M. Keller, PhD

November 01, 2013

BRUSSELS— Anal dysplasia is frequent in HIV-positive men who have sex with men. Longer sustained control of HIV is associated with less high-grade anal intraepithelial neoplasia, according to a recent study.

"Among patients with abnormal cytology, 83% had abnormal biopsy, including half with high-grade anal intraepithelial neoplasia," said Agnès Libois, MD, from the infectious disease service at the Saint-Pierre University Hospital in Brussels.

She explained that anal cancer is caused by infection with high-risk types of the human papillomavirus (HPV) and is preceded by high-grade dysplasia. Anal cancer occurs at a younger age in people who are HIV-positive than in those who are not (about 40 vs 60 years). In HIV-positive men, the prevalence of anal HPV might be as high as 95%, whereas in heterosexual men, it is 60%.

Dr. Libois presented the study results here at the 14th European AIDS Conference.

The prospective study evaluated 425 HIV-positive men who have sex with men who underwent anal cytology screening. If the results were abnormal, patients were referred for high-resolution anoscopy and biopsy. Biopsy histologies were classified as normal or as anal neoplasia grades 1, 2, or 3, with 3 being a cancer precursor.

The screened population was 90% white, mean age was 44.5 years (range, 22 - 71 years), 85% were on antiretroviral therapy, 73% had a viral load below 50 copies/mL, and median CD4 count was 632 cells/μL. The median duration of HIV was 7.5 years, and the median time on antiretroviral drugs was 7.0 years.

Of the 382 smears of sufficient quality for analysis, 48% were abnormal, according to the modified Bethesda System — 19% were atypical squamous cells of undetermined significance, 4% were atypical squamous cells where a high-grade lesion could not be ruled out, 22% were low-grade squamous intraepithelial lesions, and 3% were high-grade squamous intraepithelial lesions.

Patients with normal cytology were more likely to have undetectable viral loads than those with abnormal cytology (82% vs 62%; P < .001), and were taking combination antiretroviral therapy for a longer period of time (111 vs 49 months; P = .002). There was no correlation between cytology and age or current or nadir CD4 count.

Of the 118 high-resolution anoscopy with biopsies performed on the 183 patients with abnormal cytology, 17% of the biopsies were normal, 33% were neoplasia 1, and 39% were neoplasia 2/3. Interestingly, the high-grade specimens fell into all 4 Bethesda System abnormal cytology categories. Neoplasia 2/3 did not correlate with age, current CD4 count, or HIV viral load.

Table. Risk Factors for High-Grade Anal Neoplasia on Multivariate Analysis

Risk Factor Odds Ratio 95% Confidence Interval P Value
Nadir CD4 <100/μL 2.80 1.20–6.30 .014
Shorter duration with median HIV viral load <50/mL 0.96 0.94–0.98 .040
Age 0.97 0.94–1.00 .160


Dr. Libois concluded that anal dysplasia and high-grade neoplasia are frequent in HIV-positive men who have sex with men, and cytology with or without biopsy is the only way to detect lesions. Normal cytology "was associated with an undetectable viral load and a longer duration of combination antiretroviral therapy," whereas the risk for neoplasia 2/3 was increased with a nadir CD4 count below 100 cells/μL and a shorter time with an undetectable viral load.

"Longer sustained HIV control was associated with less anal neoplasia 2/3," Dr. Libois said, but it is an open question whether early initiation of antiretroviral therapy decreases the incidence and prevalence of anal cancer in this population.

She noted that most studies have shown that combination antiretroviral therapy has no effect on anal dysplasia, but the duration of therapy was often 2 years or less. Some recent studies with a longer duration of therapy have shown a beneficial effect, and one showed that a longer time with an undetectable viral load and a higher nadir CD4 count were associated with a lower incidence of anal squamous cell cancer.

These researchers "are essentially reporting the exact same prevalence and the high level of HPV anal intraepithelial neoplasia" as seen in the Chelsea and Westminster cohort study from London (Curr Opin HIV AIDS. 2009;4:64-67), said session chair Fiona Mulcahy, MD, from St. James's Hospital of Trinity College in Dublin, Ireland.

"You could spend your whole life in a clinic doing anoscopy and doing high-resolution anoscopy and biopsy, but actually there are no clear patterns of management for advanced disease. Our problem is that with anal intraepithelial neoplasia, there's no specific intervention that seems to be curative because of the recurrence rates," she told Medscape Medical News.

She said that many studies, but not all, have shown that CD4 cell nadir seems to have an impact. In addition, as Dr. Libois's team showed, the longer patients are on treatment, the less likely they are to have high-grade lesions. However, there are conflicting results on this point. Anal neoplasia "seems to be advancing irrespective of our control, which is also a bit of a worry," Dr. Mulcahy said.

As the data stand, she said, they do not push her to start treating everyone early with antiretroviral therapy.

There was no commercial funding for the study. Dr. Libois reports no relevant financial relationships. Dr. Mulcahy reports work with AbbVie, BMS, Merck, and GSK, and Gilead.

European AIDS Clinical Society: 14th European AIDS Conference: Abstract PS6/3. Presented October 17, 2013.


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