The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.
It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.
The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.
All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.
Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.
The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.
Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.
In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.
A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.
The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).
No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.
Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.
The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.
The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.
Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.
One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.
This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.