Gardasil protects against recurrence of pre-cancerous anal lesions in HIV-negative gay men

The genital wart vaccine Gardasil significantly reduces the risk of high-grade pre-cancerous anal lesion recurrence in men who have sex with men, US investigators report in the online edition of Clinical Infectious Diseases.

The vaccine reduced the risk of lesion recurrence by approximately 50% in the first two years after immunisation. There was some evidence that the protective effects of the vaccine waned after this point.

“This is the first study to demonstrate an association between Gardasil after primary disease and decreased risk of recurrent HGAIN [high-grade intraepithelial neoplasia],” comment the investigators, who believe the vaccine may be “an effective post-treatment adjuvant to prevent recurrent HGAIN”.

High-risk strains of human papillomavirus are the main cause of anal and cervical cancer. The quadrivalent human papillomavirus vaccine (Gardasil) is highly effective at preventing infection with these strains. Rates of anal cancer are elevated in gay and other men who have sex with men.

However, studies into the vaccine’s effectiveness recruited younger patients with no history of human papillomavirus-related disease. Little information is available on the vaccine’s ability to prevent the recurrence of high-grade pre-cancerous cell changes in the anus.

Investigators in New York therefore undertook a study involving a cohort of 202 middle-aged HIV-negative gay and other men who have sex with men, all of whom had undergone therapy for human papillomavirus-related high-grade pre-cancerous anal cell changes.

A total of 88 men (44%) were vaccinated with Gardasil; the remaining men were unvaccinated. Investigators compared the risk of the recurrence of pre-cancerous lesions after one, two and three years in the vaccinated and unvaccinated men.

The study was conducted between 2007 and 2010.

Men who received the vaccine were significantly younger than those who remained unvaccinated (37 vs 42 years, p = 0.02).

High-grade pre-cancerous lesions recurred in 12 vaccinated men and 35 unvaccinated men. The rates of recurrence in the vaccinated men was 10.2 per 100 person-years, against an incidence of 15.7 per 100 person-years in the unvaccinated individuals.

The investigators first set of statistical analysis examined the factors associated with the recurrence of disease after two years. Infection with high-risk strains of human papillomavirus had a significant association with the recurrence of anal lesions (p = 0.003). In contrast, Gardasil significantly reduced the risk of disease recurrence (p = 0.05).

Multivariate analysis that took into account potential confounding factors confirmed that infection with high-risk virus strains increased the risk of disease recurrence after one (p = 0.006), two (p =0.004) and three years (p = 0.003).

This same analysis showed that the risk of recurrence was reduced by Gardasil after one (p = 0.01) and two years (p = 0.05) of follow-up. However, the protective effect of the vaccine after three years was of only borderline significance (p = 0.06).

Analysis was then restricted to the 105 patients who tested positive for high-risk strains of human papillomavirus. A total of 47 (45%) patients received the vaccine.

The incidence of disease recurrence was 15.4 per 100 person-years in the vaccinated patients, compared to 28.3 per 100 person-years in the unvaccinated men.

Once again, the vaccine was found to significantly reduce the risk of disease recurrence after one and two years (p = 0.02 and p = 0.05 respectively) and the protective effect was of borderline significance at year three (p = 0.06).

At year one, the vaccine reduced the risk of disease recurrence by 60% (HR = 0.40; 95% CI, 0.19-0.86); by 53% at year two (HR= 0.47; 95% CI, 0.22-1.00); and by 52% at year three (HR = 0.48; 95% CI, 0.22-1.04).

“MSM with a history of treated HGAIN who received [Gardasil] had a decreased risk of recurrent HGAIN compared to men who did not receive the vaccine,” write the authors.

However, they add: “Whereas [Gardasil] appears effect in preventing recurrent disease, it is not effective at preventing all recurrence.” They believe that this disease could have been associated with non-high-risk strains of virus, or have reoccurred because “viral integration into the host genome had already occurred and the vaccine is not effective after integration.”

The authors believe their findings are potentially of public health significance. “If our results are confirmed by a randomized, placebo-controlled trial, then indications for vaccination and the age of the target population should be expanded.”

Swedish KA et al. Prevention of recurrent high-grade anal neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clin Infect Dis, online edition. DOI: 10.1093/cid/cir1036, 2012 (click here for the free abstract).