At its October 2011 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended to the CDC that quadrivalent human papilloma virus vaccine (HPV4, Gardasil) be routinely given to all males ages 11 to 21 and to men ages 22 to 26 who have sex with men or who are HIV positive, if they have not been previously vaccinated. This replaces a 2009 recommendation that stated HPV4 vaccine could be used in males to prevent genital warts, but stopped short of advocating routine use for all males.1
There were 3 reasons the previous recommendation did not include HPV4 for routine vaccination of males:
- The vaccine had been shown to be effective only for prevention of genital warts.
- The cost effectiveness of the vaccine for use in boys was poor and, in modeling, it yielded less benefit as more females were vaccinated.
- It was thought that a more effective approach to preventing HPV disease would be to emphasize high rates of vaccination of females.
The new recommendation takes into account recent evidence demonstrating that the vaccine prevents anal intraepithelial neoplasia (AIN) in males, in addition to genital warts. Moreover, vaccination rates in females remain low, which makes vaccinating males more cost effective and additionally protective for females.
Female vaccination rates lower than expected
Despite its effectiveness and safety record, HPV vaccination has had a slow rate of acceptance among females ages 13 to 17 years. Coverage for this group documented in the last national vaccine survey was 48.7% for one dose and 32% for the recommended 3 doses.2
The vaccine is effective in preventing cervical intraepithelial neoplasia (TABLE 1),3 condyloma, and vaginal intraepithelial neoplasia in women ~15 to 26 years of age. Large studies of vaccine safety have documented no serious adverse reactions, other than syncope, which could occur as frequently as 17.9/10,000 females and 12.5/10,000 males.4 Another study that involved post-licensure safety data from >600,000 HPV4 doses found no increased risk for a variety of outcomes, including Guillain-Barré syndrome, stroke, venous thromboembolism, appendicitis, seizures, syncope, allergic reactions, and anaphylaxis.5,6
TABLE 1
HPV vaccine efficacy against HPV type-related CIN2+ in females ages ~15 to 26 years3
| Vaccine/HPV type | Vaccine | Placebo | Efficacy | |||
|---|---|---|---|---|---|---|
| N | CIN cases | N | CIN cases | % | CI* | |
| Bivalent HPV 16/18 HPV 16 HPV 18 | 7344 6303 6794 | 4 2 2 | 7312 6165 6746 | 56 46 15 | 93 96 87 | 80-98 83-100 40-99 |
| Quadrivalent HPV 16/18 HPV 16 HPV 18 | 7738 6647 7382 | 2 2 0 | 7714 6455 7316 | 100 81 29 | 98 98 100 | 93-100 91-100 87-100 |
| CI, confidence interval; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus. *Confidence interval for bivalent results was 96.1%, and for quadrivalent results was 95%. | ||||||
HPV-associated disease in males
HPV causes anal, penile, and oropharyngeal cancers in males, with about 7500 cancers occurring each year in the United States.3 In addition, about 1% of sexually active males in America have genital warts at any one time.7 HPV types 6 and 11 cause about 90% of cases.1
The HPV4 vaccine—when all 3 doses are given—is 89.3% effective in preventing genital warts related to HPV types 6 and 11. Even a single dose is 68.1% effective (95% CI, 48.8–80.7).1 New evidence shows that HPV4 prevents AIN, which can lead to anal cancer.8 Effectiveness in preventing AIN 2/3 is 74.9% (95% CI, 8.8–95.4) in those completing 3 doses before onset of infection with one of the HPV types contained in vaccine. Notably, these results were obtained in a subgroup analysis of men who have sex with men. And although the reduction in AIN is expected to lower the incidence of anal cancer, ongoing studies require time to confirm this. If such a reduction is confirmed (and vaccination is started at age 12 in the general male population), the number-needed-to-vaccinate to prevent one case of genital warts would be 18, and to prevent one case of anal cancer, 1581.6
No studies have evaluated efficacy of HPV4 in preventing penile or oropharyngeal cancers.
Men who have sex with men at high risk
Men who have sex with men have higher rates of AIN, anal cancers, and genital warts than the general male population.3 Those who are additionally HIV positive have higher rates of genital warts, which are also more difficult to treat.3 AIN is also more common in HIV-infected males.3 The HPV4 vaccine is immunogenic in those who are HIV infected, although the resulting antibody titers are lower than in other populations.
A look at the 2 HPV vaccines
Two HPV vaccines are available (TABLE 2).3 HPV4 vaccine protects against HPV 6, 11, 16, and 18. Bivalent (HPV2, Cervarix) vaccine contains antigens from HPV 16 and 18. Both vaccines are approved for use in females for the prevention of cervical cancer; HPV4 is preferred if protection against genital warts is also desired. Only HPV4 has been licensed for use in males.