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HPV-16 Tied to Development and Clearance of Anal Cancer Precursor in Gay HIV+/HIV- Men
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7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
Testing positive for human papillomavirus type 16 (HPV-16), a high-risk HPV type, raised chances that anal high-grade squamous intraepithelial lesions (HSIL) would develop in gay men with or without HIV and lowered chances of clearing HSIL [1]. The findings suggest that HPV testing could help identify men at high risk for HSIL, an anal cancer precursor.
Anal cancer rates have been climbing among HIV-positive men and now exceed rates of cervical cancer (also caused by HPV) before organized cervical cancer screening programs. Anal cancer screening advice remains controversial. Sydney and Melbourne researchers who conducted this HSIL study observed that some experts recommend an approach analogous to cervical cancer screening--anal cytology followed by high-resolution anoscopy guided by biopsy to detect and treat precancerous HSIL. But scanty evidence on the natural history of HSIL prevents wide endorsement of this approach.
The Australian team planned this study to assess prevalence, incidence, and clearance of anal HSIL--in relation to HPV type--in a cohort of HIV-positive and negative men in Sydney. SPANC, the Study of the Prevention of Anal Cancer, is a 3-year community-recruited prospective study of the natural history of anal HPV infection and anal cellular abnormalities in gay men at least 35 years old.
Study participants undergo liquid-based anal cytology followed by high-resolution anoscopy at a baseline visit and at months 6, 12, 24, and 36. Visible abnormalities prompt biopsy for histologic assessment. The investigators defined HSIL as either anal intraepithelial neoplasia grade 2 or 3 (AIN 2/3) on histology or HSIL on cytology. They also genotyped cytologic samples for high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68; they considered HPV-16 and HPV-18 as risk factors for HSIL incidence and clearance.
Between September 2010 and March 2013, the SPANC team recruited 342 men with a median age of 49 (range 35 to 79). Ninety-eight men (29%) were HIV-positive, of whom 87 (89%) were on antiretroviral therapy and 82 (84%) had an undetectable viral load. Most HIV-positive men (83%) had a recent CD4 count above 350.
At the baseline visit, 128 men (37.4%) had anal HSIL. Prevalence was nonsignificantly higher in men with HIV than in HIV-negative men (44.9% versus 34.4%, P = 0.072). Among the 149 men without HSIL at their initial visit, anal HSIL developed in 32 (21.5%) after an average 1.0 person-years of follow-up. Seven of these cases progressed from a normal baseline status and 25 from low-grade AIN. Overall anal HSIL incidence was 21.5 per 100 person-years (95% confidence interval [CI] 15.2 to 30.4), meaning HSIL developed in 21 or 22 of every 100 men every year.
Among 80 men who had anal HSIL at their baseline visit and had at least one follow-up visit, HSIL regressed to normal in 14 and to low-grade lesions in 21 after an average 1.0 person-year of follow-up. Overall HSIL clearance stood at 43.5 per 100 person-years (95% CI 31.3 to 60.6). Thirty of 35 HSIL that regressed affected only one quadrant. HSIL affecting multiple quadrants was almost 75% less likely to regress (hazard ratio 0.27, 95% CI 0.10 to 0.70).
Neither age nor HIV status predicted incident HSIL or HSIL clearance. But baseline positivity for high-risk HPV, HPV-16, or HPV-18 raised the risk of incident HSIL, and high-risk HPV or HPV-16 positivity lowered chances of HSIL clearance, at the following hazard ratios (and 95% CIs):
Hazard ratio for incident HSIL:
High-risk HPV-positive at baseline: 4.35 (1.67 to 11.35), P = 0.003
HPV-16-positive at baseline: 3.00 (1.46 to 6.16), P= 0.003
HPV-18-positive at baseline: 5.00 (1.73 to 14.44), P = 0.003
Hazard ratio for HSIL clearance:
High-risk HPV-positive at baseline: 0.36 (0.17 to 0.75), P = 0.006
HPV-16-positive at baseline: 0.20 (0.08 to 0.49), P < 0.001
The researchers concluded that "both incidence and clearance of HSIL were common and were closely associated with high-risk HPV and HPV-16 status." They proposed that high anal HSIL clearance rates "are consistent with the observation that anal HSIL progresses to cancer less commonly than high-grade cervical lesions."
The significant association between HSIL persistence and HPV-16 positivity suggested to the Australian team that HPV testing should be studied as a way to identify men with HSIL who run a high risk of anal cancer.
Two HPV vaccines, Cervarix and Gardasil, protect against HPV-16 and 18. The CDC recommends HPV vaccination for gay and bisexual men and for men and women with HIV through age 26 [2].
References
1. Jin F, Poynten IM, Machalek D, et al. High prevalence, incidence and clearance of anal high-grade squamous intraepithelial lesion (HSIL): early evidence from a natural history study in homosexual men. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract WEPDB0104. http://pag.ias2013.org/EPosterHandler.axd?aid=1224
2. Centers for Disease Control and Prevention. Human papillomavirus (HPV). HPV vaccines. http://www.cdc.gov/hpv/vaccine.html
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