Anal Cytology Has High False-Negative Rate in MSM With or Without HIV

More than one-third of anoscopically detected grade 2 or worse anal intraepithelial neoplasia (AIN) lesions in men who have sex with men (MSM) came from men with negative cytologic results in a study of 284 UK MSM who had receptive anal intercourse. Biopsies from anoscopy confirmed AIN3 or worse in 7% of MSM with HIV and 4% of HIV-negative men.

Meta-analysis confirms a high prevalence of high-grade AIN in MSM, driven by anal sex and infection with human papillomavirus type 16 (HPV-16). Liquid-based cytology, HPV testing and high-resolution anoscopy can detect anal neoplasia, particularly in MSM with HIV. But the value of detecting and treating AIN as a way to prevent anal cancer remains undetermined. A British group conducted this prospective study to assess the feasibility and acceptability of anal screening in MSM with or without HIV. The results were published in the June 1 issue of AIDS.

Researchers recruited MSM at sexual health clinics from March 2013 through March 2015. No men had previous anal screening. All participants had anal swabs to collect samples for cytology, followed by a digital rectal exam and anoscopy. Lesions detected by anoscopy were biopsied and classified as AIN1, AIN2 or AIN3. AIN1 approximates low-grade squamous intraepithelial lesions (LSIL) and AIN2/3 high-grade SIL (HSIL). Men with AIN3 or worse (AIN3+) were referred for management, usually excision. The investigators tested anal swab samples for HPV-16 and HPV-18 and genotyped positive samples for HPV-16 and eight low-risk HPV types.

The study involved 284 MSM, 203 (71%) with HIV and a median age of 42 years, and 81 men without HIV and a median age of 38 years. Large majorities of men with and without HIV (almost 90% and 70%) had receptive anal intercourse for more than 10 years. High-risk HPV could be detected in 88% of men with HIV and 78% of men without HIV.

Among men with and without HIV, 46.2% and 35% had abnormal cytologic results. Anoscopy detected HSIL in 10.56% of all MSM and LSIL in 31.34%. More than one-third of AIN2 or worse (AIN2+) cases had negative cytology, including five of 17 cases of AIN3+ (29%). Cytology had a sensitivity of only 62.9% to detect AIN2+ and 76.5% to detect AIN3+. Specificity was 60.0% for AIN2+ and 54.6% for AIN3+. Detection of high-risk HPV had 94% sensitivity to detect both AIN2+ and AIN3+, but specificity was only 16.9% for AIN2+ and 13.9% for AIN3+.

On the basis of these findings, the researchers rated the clinical utility of cytology and high-risk HPV "relatively poor," even when they combined the tests. Still, an analysis adjusted for age, smoking, alcohol, HIV status and HPV status determined that a borderline or greater cytologic result independently doubled the odds of AIN2+ (adjusted odds ratio [aOR] 2.37, 95% confidence interval [CI] 1.24 to 4.52, P = .009). HPV positivity also doubled the odds of AIN2+, but this association lacked statistical significance (aOR 2.35, 95% CI 0.73 to 7.61, P = .153).

Among the 284 study participants, 204 (72%) had a biopsy because of anoscopic abnormalities. Prevalence of AIN3+ was 6.9% in HIV-positive men and 3.7% in HIV-negative men. Respective rates of AIN2+ were 26.6% and 20.99%. Three men with HIV had microinvasive cancer.

On a scale of 0 to 10 indicating no pain to worst pain ever, study participants gave the procedures an average score of 3.7 at the time of the test and 3.8 following the test. Pain lasted an average of three days. Men reported little or no psychological distress awaiting the results of their screenings (average 2.5 on a scale of 0 to 10). And 92% of men said they would undergo anal screening again.

The authors believe their results show that "anal screening is both feasible and acceptable amongst MSM who have anoreceptive sex." But the low sensitivity of cytology in predicting AIN2+ suggests that it has little value as a "stand-alone screening test." Because HIV-positive MSM make up only 5% of MSM and have a high prevalence of anal disease, the researchers suggest they "represent the most cost-effective group to screen." But even if screening were limited to MSM with HIV, "the extent to which cancer could be prevented and lives saved remains uncertain."

A randomized trial is currently recruiting participants to determine whether detecting and treating biopsy-proved HSIL in men and women with HIV prevents anal cancer.