HPV vaccine for boys and men?

It could help reduce incidence of cervical and head and neck cancers

Now that the Food and Drug Administration (FDA) is expected to approve Merck's Gardasil for use in boys and men, several physicians are optimistic that the vaccine will further reduce the incidence of both cervical and head and neck cancers.

“It's great news in terms of our opportunity to use the same vaccine to reduce cancers in both males and females,” says Anna Giuliano, PhD, chair of cancer epidemiology and genetics at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. “We're really changing our approach to cancer prevention by using vaccines.

Dr. Giuliano is an international consultant for the men's human papillomavirus (HPV) vaccine program for Merck. She served as principal investigator for the Merck-sponsored clinical trial for Gardasil in males, for which Moffitt was a site. In addition, the National Institutes of Health awarded her $10 million for a study to determine men's role in the spread of HPV that causes cervical cancer.

Gardasil was approved for use in the US in June 2006 and is indicated for use in girls and young women ages 9 through 26 years for the prevention of cervical, vulvar, and vaginal cancers caused by HPV 16 and 18, as well as for genital warts caused by HPV types 6 and 11 and precancerous dysplastic lesions cause by HPV types 6, 11, 16, and 18.

At press time, the FDA was likely to approve Gardasil for use in boys and men ages 9 through 26 years for the prevention of genital warts caused by HPV types 6 and 11. The FDA generally (though not always) follows the recommendations of its Vaccines and Related Biological Products Advisory Committee, which met September 9, 2009, to review Merck's application.The committee recommended approval based on its assessment that efficacy, immunogenicity, and safety data from clinical trials supported use of the vaccine in males.

Vaccine efficacy in males was evaluated in a randomized, double-blind, placebo-controlled trial of 4,055 men. Study results showed that the vaccine was 89% effective against HPV types 6 and/or 11 (related to genital warts) and 90.4% effective against the HPV types 6,11,16, and 18 (combined clinical endpoints for genital warts and precursor lesions for penile cancer).The study showed no serious side effects; the most common complaint was pain at the injection site.

At press time, the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) was scheduled to meet in October to discuss and make clinical recommendations for the HPV vaccine in males. Medical societies and academies generally develop their guidelines based on the ACIP's recommendations.

Dr. Giuliano notes that, “the data are very promising that lead us to believe the vaccine will help us prevent HPV 16- and 18-related cancers in men.” She adds that, “because we know this is a sexually transmitted infection, we think that preventing this infection in men will reduce infection in females as well.”

At this point, while neither of these theories has been proven in clinical studies, several experts believe giving the HPV vaccine to males may have this added benefit. “We are in the midst of a tonsil and base-of-tongue cancer epidemic,” says Carol Bradford, MD, chair of otolaryngology and director of head and neck oncology at the University of Michigan Comprehensive Cancer Center in Ann Arbor. “We believe upwards of 75% of throat cancers seen today are related to HPV infection.”

Dr. Bradford says that, while throat cancer is still a relatively rare cancer, it is the most frequent type of head and neck cancer her clinic sees—approximately several hundred cases each year. These types of cancers are associated with HPV type 16. “Changing sexual mores and an increase in oral sex has allowed the epidemic to increase” she notes.

The connection was first demonstrated by Maura Gillison, MD, the Jeg Coughlin chair in cancer research at Ohio State Medical Center in Columbus, a leading researcher in the field who also identified multiple sexual partners as the most important risk for these cancers. “It is currently accepted that a proportion of anal, oropharyngeal, vulvar, and vaginal cancers among women and anal, oropharyngeal, and penile cancers among men are etiologically related to HPV,” Dr. Gillison and colleagues concluded in a paper published in Cancer.1

She added that, “Given that a substantial proportion of cervical cancers (approximately 70%) and an even greater proportion of HPV-associated noncervical cancers (approximately 86% to 95%) are caused by HPV 16 and 18 (HPV types that are targeted by the currently available vaccines), current HPV vaccines may hold great promise (provided equivalent efficacy at all relevant anatomic sites) in reducing the burden of HPV-associated noncervical cancers, in addition to cervical cancers.“

Dr. Bradford believes that even if not every child receives the HPV vaccine, the result will be a “herd effect” leading to fewer people transmitting the HPV virus that is linked to these cancers. “There are so few opportunities in our society where we can use a vaccine to prevent the later development of cancer” she says. “We live for these types of breakthroughs.”

Adds Thom Lorec, MD, chair of head and neck surgery at the Roswell Park Cancer Institute in Buffalo, New York, if everyone stopped smoking and using tobacco of any form and also got vaccinated against HPV, “we could eliminate head and neck cancers.”

Even if the FDA approves Merck's application as expected and the ACIP issues broad recommendations for use, it still is not known whether most insurers will cover the vaccine's cost or if parents will decide to have their sons vaccinated.