Human papilloma virus (HPV) is the sexually-transmitted organism that is the most common cause of anogenital warts and cancers—depending on gender—of the cervix, penis, mouth, and anus. Research on HPV prophylaxis has traditionally focused on females, since cervical cancer is the most prevalent of the virus’ oncogenic outcomes. A four-pronged vaccine against some of the most important strains has become standard of care for girls and women ages 9 to 26, while the debate about vaccinating males has centered on reducing transmission to females.
A paper in this week’s NEJM highlights how males can benefit from the vaccine directly.
While both genders are equally likely to become infected with HPV, males mount a weaker antibody response to the virus and have a higher prevalence of infection. A multi-national study by Giuliano et al. provides good evidence that the quadrivalent vaccine, developed by study sponsor Merck, elicits HPV immunity in this population.
Researchers based at H. Lee Moffitt Cancer Center and Research Institute and at the University of California, San Francisco report on the FDA-approved vaccine against HPV-6, 11, 16, and 18 in boys and men. The researchers enrolled 4065 healthy male subjects between 16 and 26 years of age in a randomized, placebo-controlled, double-blind study to investigate whether the vaccine would reduce the incidence of external genital or anogenital lesions—warts, pre-cancerous lesions, or cancer—and of infection persisting six months or longer.
In the intention to treat population, the vaccine group developed 36 external genital lesions—mainly warts—compared to 89 in the placebo group—indicating an observed efficacy of 60.2%. The efficacy was slightly higher, at 65.5%, for lesions related to the four targeted strains, though the vaccine did not significantly reduce the incidence of lesions associated with strains 16 and 18 (associated with cancer), nor with pre-cancerous lesions (there were no cases of cancer in the trial). Out of 2805 subjects in the per protocol population, there were three cases of vaccine type-related lesions, representing an efficacy in this sub-group of 90.4%.
The vaccine’s efficacy against persistent infection with these strains was 47.8% in the intention-to-treat population and 85.6% in the per-protocol population.
The authors excluded subjects with more than five sexual partners over their lifetimes, and those with existing genital lesions, HPV-related or otherwise—which may have led to overrepresentation of subjects with low likelihood of exposure to the virus. This issue is less significant if the vaccine is given prior to sexual debut, which is how it is currently recommended to be given to women. As NEJM Deputy Editor Lindsey Baden notes, “Data have emerged suggesting that the HPV vaccine is reasonably effective if given prior to but not after exposure to the given HPV serotype.”
The study provides important evidence that the vaccine protects young men against persistent HPV infection and anogenital warts, which are of public health concern but nonetheless hardly fatal. The question of whether it can prevent more severe disease, including cancer, is left unanswered. Still, says Baden, it’s “good to curtail transmission of oncogenic serotypes” to women and men, especially since these strains may have far-reaching oncogenic effects in both sexes that would be difficult to capture in a several year study.
In a related Perspective, Jane J Kim, PhD writes about the hotly debated ups and downs of routine HPV vaccination for males. She concludes: “The report by Giuliano et al. undoubtedly gives us cause to celebrate the extraordinary potential for HPV vaccination to improve health in both women and men. And although enthusiasm for universal vaccination may initially be tempered by uncertainties about the vaccine’s safety, efficacy, and duration of protection (as well as its uptake, acceptability, and cost), many of these factors could very well change in the future.”
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Should guidelines change to recommend vaccination for young men?