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Anal Cancer Precursor More Common in HIV+
Than HIV- MSM; Clearance Rate High
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20th International AIDS Conference, July 20-25, 2014, Melbourne
Mark Mascolini
High-grade squamous intraepithelial lesions (HSIL), an anal cancer precursor, proved more common in HIV-positive than HIV-negative men who have sex with men (MSM) in an interim analysis of a prospective Australian cohort [1]. Testing positive for human papillomavirus (HPV) type 16 tripled the risk of new HSIL. And HSIL clearance rates were high in men with and without HIV.
Anal cancer remains common in HIV-positive men and women in the current antiretroviral era. Researchers from the University of New South Wales noted that 30% to 50% of HIV-positive MSM have HSIL, an anal cancer precursor. Whether people with HSIL should undergo ablative therapy versus close monitoring remains controversial because treatment carries some risk, recurrence rates are high, and HSIL does not invariably result in anal cancer.
To shed more light on this question, Andrew Grulich and colleagues are determining the incidence, clearance, and risk factors for anal HSIL in HIV-positive and negative MSM enrolled in the Sydney-based Study of the Prevention of Anal Cancer (SPANC), a prospective cohort study of the natural history of anal HPV and its precursors. All study participants are at least 35 years old. At 5 study visits over 3 years, men have an anal swab for cytology and HPV genotyping, followed by high-resolution anoscopy-directed biopsy for histologic assessment and biopsy of visualized abnormalities. The investigators aim to recruit 600 men by July 2015. They define HSIL as anal intraepithelial neoplasia grade 2 or 3 on histology and/or HSIL on cytology.
This interim analysis involved 450 men recruited through June 2014. Median age stood at 49 years, and 139 (31%) had HIV infection. At the baseline study visit, HSIL prevalence measured 46% in men with HIV and 34% in men without HIV, a significant difference (P = 0.014).
Among 197 men without HSIL at the baseline visit, HSIL developed in 45 men for an incidence of 16 per 100 person-years. (Incidence of 16 per 100 person-years means HSIL developed in 16 of every 100 men every year.) HSIL incidence was almost twice higher in men with HIV (22.5 versus 13.1 per 100 person-years), a nearly significant difference (P = 0.061). Compared with men who had normal anal cytology at the baseline visit, those with low-grade squamous intraepithelial lesions had a tripled risk of HSIL (hazard ratio [HR] 3.00, 95% confidence interval [CI] 1.41 to 6.38) and those with ASC-H (atypical squamous cells and inability to rule out HSIL) ran more than a 6 times higher risk (HR 6.61, 95% CI 2.93 to 14.9).
Research shows that, among HPV genotypes, HPV-16 carries the highest risk of anal cancer. HSIL incidence was 37.1 per 100 person-years in men positive for HPV-16 at baseline and 11.6 per 100 person-years in men negative for HPV-16 at baseline. Those numbers translated into a tripled risk of HSIL in men positive for HPV-16 at the baseline visit (HR 3.14, 95% CI 1.71 to 5.74, P = 0.001). Men positive for HPV-16 at baseline and their latest visit ran a 6-fold higher risk of HSIL than men negative for HPV-16 at both visits (HR 6.09, 95% CI 3.02 to 12.3, P < 0.001). HPV-18 positivity at the baseline visit quadrupled chances of incident HSIL (HR 4.21, 95% CI 1.85 to 9.57, P = 0.001). (The quadrivalent and bivalent HPV vaccines target both HPV-16 and HPV-18. US authorities recommend the vaccine for HIV-positive and negative boys and girls and men and women up to age 26 [2].)
Among men who had HSIL at the baseline visit, clearance rates were nearly identical in men with and without HIV (41.7 and 41.8 per 100 person-years, P = 0.831). HPV-16-positive men had almost a 70% lower chance of clearing HSIL (HR 0.32, 95% CI 0.19 to 0.55, P < 0.001). Men with any high-risk HPV genotype had almost an 80% lower chance of clearing HSIL (HR 0.22, 95% CI 0.12 to 0.40, P < 0.001). Men persistently positive for any high-risk HPV type or for HPV-16 were significantly less likely to clear HSIL than negative men.
The Australian team concluded that HSIL is highly prevalent in HIV-positive and negative MSM and highly dynamic, with an overall incidence of 16 per 100 person-years and overall clearance of 42 per 100 person-years. The high clearance rate, they proposed, implies that not all HSIL requires treatment. They suggested targeting treatment for men with persistent HSIL.
Because high-risk HPV positivity predicts both incidence and clearance of HSIL, the researchers suggested that "repeated HPV testing has a role in the full assessment of HSIL before treatment." They called for more research on the role of HPV biomarkers that predict persistent infection.
A US trial that aims to enroll 5000 HIV-positive men and women with HSIL will randomize them to topical or ablative treatment versus close observation to determine whether treating HSIL lowers anal cancer incidence [3].
References
1. Grulich AE, Jin F, Poynten IM, et al. Incidence and clearance of anal high-grade squamous intraepithelial lesions (HSIL) in HIV positive and HIV negative homosexual men. AIDS 2014. 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract WEAB0102.
2. Centers for Disease Control and Prevention. Human papillomavirus (HPV) ACID vaccine recommendations. http://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/hpv.html
3. ClinicalTrials.gov. Topical or ablative treatment in preventing anal cancer in patients with HIV and anal high-grade squamous intraepithelial lesions. http://clinicaltrials.gov/ct2/show/NCT02135419
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