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IAS 2013: HPV Vaccination May Prevent Anal Cancer in Older Gay Men

A large number of infections with anal cancer-associated strains of human papillomavirus (HPV) among older gay men could be prevented with the use of HPV vaccines, Australian research reported at the recent 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur. A related analysis showed that high-grade pre-cancerous cell changes were common but often resolved spontaneously.

[Produced in collaboration with Aidsmap.com]

Investigators with the Study of the Prevention of Anal Cancer (SPANC) in Sydney undertook the research because of the high prevalence of anal HPV infection among gay men, especially those with HIV.

Persistent infection with a high-risk strain of HPV can lead to anal cell changes that can progress to cancer. The rate of anal cancer is high among HIV positive gay men, at 100 cases per 100,000.

The quadrivalent HPV vaccine (Gardasil) provides a high degree of protection against infection with HPV types 6, 11, 16, and 18. Types 6 and 11 cause genital warts, while types 16 and 18 are associated with anal and genital cancers.

In Australia, the quadrivalent vaccine has been recommended for school-age girls since 2007 and for boys since 2013. The vaccine is approved for women up to the age of 45, but recommended only for men aged 26 and under, due to a lack of data in older male populations.

A nonavalent HPV vaccine is currently being developed by Merck and Co. This vaccine is designed to provide protection against a broader spectrum of 9 HPV genotypes including HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Investigators wanted to establish the potential impact of immunization with quadrivalent or nonavalent vaccines on the incidence of anal HPV infection among older gay men. They especially wanted to see if HIV infection and age were risk factors for infection with high-risk strains of HPV.

A total of 342 gay men aged 35 and older were recruited into the study between 2010 and 2013. They were screened at baseline for infection with HPV types covered by the quadrivalent and nonavalent vaccines. Over 3 years of follow-up, the participants were also examined for incident or new high-risk HPV infections.

The participants had a mean age of 49 years (range 35 to 79) and 29% were HIV positive. The vast majority (89%) of HIV positive men were taking antiretroviral therapy. This treatment was achieving good control of HIV, with 84% having an undetectable viral load and 83% having a recent CD4 cell count above 350 cells/mm³.

At baseline, 51% of men were infected with an HPV type covered by the quadrivalent vaccine and two-thirds with a strain preventable by the nonavalent vaccine. The most prevalent type was HPV16 (the most common type associated with anal cancer), which was detected in 30% of participants.

Over the 3 years of the study, there was a high incidence of infection with cancer-associated HPV types. One-fifth of men each year became newly infected with a strain of HPV covered by the quadrivalent vaccine and 27% with a type covered by the nonavalent vaccine.

The HPV type most commonly associated with genital warts (HPV6) was the most frequently detected type in new infections (9 per 100 person-years), followed by 2 high-risk oncogenic HPV types, HPV45 (8 per 100 person-years) and HPV16 (5 per 100 person-years).

HIV infection was a significant risk factor for the presence of high-risk HPV types at baseline and incident HPV infections during follow-up. There were no significant associations with age.

The investigators therefore concluded that there is a high prevalence and incidence of HPV strains covered by both vaccines among older gay men, especially among men with HIV. They believe their findings could have implications for vaccination strategies, as "prophylactic [quadrivalent] HPV and [nonavalent] HPV vaccination of older homosexual men would prevent future HPV-associated disease."

High-grade Dysplasia

[This report contributed by Liz Highleyman]

The SPANC team also presented a poster describing early findings from their natural history study of HPV and anal cancer. Given the high rates of anal cancer among gay men, screening and treatment of pre-cancerous changes known as high-grade squamous intraepithelial lesion (HSIL) is recommended by some experts, but is not yet widely included in HIV management guidelines.

SPANC participants receive an anal swab at each visit to check for abnormal cells (a Pap test) and to determine HPV genotypes, as well as regular high-resolution anoscopy for histological (tissue) testing; visible abnormalities (dysplasia) are further assessed with biopsies.

At baseline, the prevalence of anal HSIL was 37% overall. HIV positive men were more likely to have HSIL than negative men (45% vs 34%, respectively), but the difference fell short of statistical significance.

Among 149 men without HSIL at study entry, 22% developed HSIL over an average 1 year of follow-up. Incidence rates were 31 and 18 cases per 100 person-years for HIV positive and negative participants, respectively, but again the difference did not reach statistical significance. However, men who showed evidence of high-risk HPV infection -- HPV16 or HPV18 in particular -- at baseline were significantly more likely to develop HSIL, reaching 50 and 83 cases per 100 person-years for HPV16 and HPV18, respectively.

Among men who did have HSIL at baseline, 26% experienced regression to low-grade dysplasia and 18% experienced regression to normal without treatment. Regression was most likely when dysplasia affected only 1 quadrant of the anus. Overall regression rates were similar for HIV positive and negative men, but here too, high-risk HPV and HPV16 at baseline were associated with a lower likelihood of regression (from 81 regressions per 100 person-years for men with no high-risk HPV to only 15 for those with HPV16).

"Both incidence and clearance of HSIL were common, and were closely associated with high-risk HPV and HPV16 status," the researchers concluded.

Reassuringly, they noted, "The high rates of clearance are consistent with the observation that anal HSIL progresses to cancer less commonly than high-grade cervical lesions." They recommended that the close association between HSIL persistence and HPV16 "suggests that HPV testing should be investigated as a means of identifying those men with HSIL who are at high risk of developing anal cancer."

7/24/13

References

IM Poynten, S Tabrizi, F Jin, et al. Potential impact of human papillomavirus (HPV) vaccination among homosexual men: a review of vaccine-preventable anal HPV types in the SPANC study.7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WEPE536.

F Jin, IM Poynten, D Machalek, 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 International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WEPDB0104.