The quadrivalent HPV vaccine reduced the rate of persistent anal infection with HPV types 6, 11, 16, and 18, as well as the anal intraepithelial neoplasia associated with these viral types, in an industry-sponsored study of homosexual men reported in the Oct. 27 issue of the New England Journal of Medicine.
It is likely that the vaccine will also prevent anal cancer, but longer follow-up is needed to make that determination, said Dr. Joel M. Palefsky of the University of California, San Francisco, and his associates.
"Although our study only included men who have sex with men, our data suggest potential benefits of vaccination for women and heterosexual men, beyond the already demonstrated protection against cervical and vulvovaginal disease and external genital condyloma. ... We would expect the qHPV vaccine to protect against anal intraepithelial neoplasia [including anal condyloma] in the female and heterosexual male populations to a degree similar to that among men who have sex with men," they noted.
The incidence of anal cancer has been increasing by approximately 2% per year in both men and women in the general population. Anal condyloma is more common – one of the most common sexually transmitted diseases (STDs) in homosexual men. This condition can cause substantial psychological distress, and may be painful and expensive to treat. So the HPV vaccine’s ability to reduce anal condyloma is "a substantial added benefit," the researchers said.
Dr. Palefsky and his colleagues assessed the efficacy of the quadrivalent HPV vaccine at preventing anal lesions in 598 healthy homosexual men aged 16-26 years residing in the United States, Australia, Brazil, Canada, Croatia, Germany, and Spain. Half the subjects were randomly assigned to receive serial injections of active vaccine, and half received placebo injections over the course of 1 month.
The two groups were well-matched for age, race, ethnicity, geographic region, smoking status, circumcision status, and sexual history. Vaccine efficacy was determined at 7 months after vaccination, and the study subjects were followed for a mean of 2.2 years after that.
As expected, no cases of anal cancer developed in these young study subjects followed for a relatively short time.
The vaccine had an overall efficacy of 77.5% in preventing anal intraepithelial neoplasia or anal cancer related to HPV-6, 11, 16, or 18 in the per-protocol study population. (This included only subjects whose swab and biopsy specimens were negative for vaccine-type DNA through 7 months.) Such lesions developed in 5 men who received active vaccine and 24 who received placebo.
The vaccine was 73% efficacious against anal intraepithelial neoplasia of grade 1, including condyloma, and 74.9% efficacious against anal intraepithelial neoplasia of grade 2 or 3 in the per-protocol population.
In the intention-to-treat population, vaccine efficacy against anal intraepithelial neoplasia related to any of the four HPV types was 50.3%. "Significant reductions in both anal intraepithelial neoplasia of grade 1 (49.6%) and ... grade 2 or 3 (54.2%) were seen in the intention-to-treat population," the investigators said (N. Engl. J. Med. 2011;365:1576-85).
In addition, the vaccine reduced persistent HPV infection with an efficacy of 94.9% in the per-protocol population and 59.4% in the intention-to-treat population. Persistent infection was defined as detection of the same HPV type at two or more consecutive visits that were at least 4 months apart.
Dr. Palefsky and his associates noted that "the proportion of patients who reported serious adverse events or who discontinued the study owing to an adverse event was relatively low and was similar in the two groups." There were no vaccine-related serious adverse events and no deaths in either group.
It is important to note that these study subjects had somewhat limited sexual experience, with a maximum of five lifetime sexual partners. Thus, the findings may not be generalizable to other men who have sex with men, who tend to have more sexual partners, the researchers added.
This study was funded by Merck, maker of the Gardasil and Silgard HPV vaccines, with additional support from the National Institutes of Health. Dr. Palefsky reported ties to Merck, Pharmajet, and Aura Biosciences; his associates reported numerous industry ties.