Joel Palefsky
Merck announced late last week that its human papillomavirus (HPV) vaccine can prevent HPV infection in boys and young men. This was the first data released on how well the vaccine, called Gardasil, works in males. Joel Palefsky, MD, a UCSF professor of medicine, is one of the principal leaders of the study, part of an ongoing, worldwide clinical trial.
“The vaccine helps prevent infection and external lesions due to infection,” Palefsky says. “It has the potential to reduce transmission of the virus.”
There are 4,065 men and boys, age 16 to 26, participating in the study. The vaccine covers HPV strains 6, 11, 16 and 18. In the group that received the vaccine, there were 15 cases of persistent infection lasting six months or more with these strains. In the control group, there were 101 cases of persistent infection with these strains. For this analysis, the participants were tracked for an average of 29 months after vaccination.
In the United States, Gardasil now is most often given to schoolgirls age 9 and above. The vaccine earlier was shown in females to prevent infection by the HPV 16 and HPV 18 strains, which are responsible for 70 percent of cervical cancers. In studies of women and girls, the vaccine also prevented infection by the strains that cause 90 percent of genital warts. There are additional HPV strains associated with some cases of genital warts and cancer. The vaccine has not yet been proven to prevent actual cancer cases in men or women.
Despite the previous lack of data in males, the vaccine already is approved for use in men and boys in several countries.
Merck says it is on track for submission of an application to the Food and Drug Administration before the end of the year. The company is seeking approval to market Gardasil for use in males age 9 to 26 to prevent genital warts and precancerous growths.
The study is being conducted in men and boys with few or no lifetime sexual partners. This initial analysis included participants who showed no evidence of ever having been infected. As part of this trial, Palefsky has been studying a subset of males at UCSF – 28 young men who have had sex, or who expect to have sex, with other men. Worldwide, 602 study participants fall into this category.
Penis cancer due to HPV is rare in the United States. Vaccinating the entire male population to prevent genital warts and penile cancers each year might not prove compelling from a cost-benefit perspective. But Palefsky notes other reasons for the interest in vaccinating men.
One is so-called herd immunity. If large numbers of girls and women do not obtain the recommended vaccinations, then vaccination of men and boys could play a significant role in lowering infection rates among both males and females.
Another consideration is anal cancer, especially among men who have sex with men. A majority of HIV-positive men are chronically infected with HPV. The anal cancer incidence is rising among both men and women. Among HIV-positive men, it already is on the order of 100 new cases each year per 100,000 individuals, Palefsky says. That dwarfs the roughly nine new cases of cervical cancer per 100,000 women diagnosed each year in the United States.
In addition, there is increasing recognition that HPV is likely to play a role in some oropharyngeal cancers, which disproportionately affect men. These cancers develop later in life. The extent of the role of HPV in oral cancers is controversial.
“The evidence shows that the association between HPV and oropharyngeal cancer is strong,” says UCSF oral surgeon and cancer researcher Brian Schmidt, DDS, MD, PhD. “However, there is little to no association between HPV and oral cancer. The sites are commonly confused.” Oropharyngeal cancer may affect the tonsils or the base of the tongue. Cancer of the oral cavity may affect the rest of the tongue, the floor of the mouth, the gingiva and the palate.
The US Centers for Disease Control and Prevention (CDC) issued a press release earlier this month on a study of HPV-associated cancers in 38 states and the District of Columbia from 1993 to 2003. About 25,000 cases of cancer are attributable to HPV in these regions each year, the agency concluded. The most common include 10,800 cases of cervical cancer, 3,000 cases of anal cancer, and an estimated 7,400 cases of HPV-associated cancers of the oropharynx and oral cavity.
The Merck study of men and boys is double-blinded. This means participants and frontline physicians and researchers do not know which participants received the vaccine and which received placebo injections containing no vaccine. Merck unblinded analysts to review the data when a predetermined number of warts and precancerous growths were reported among the participants. The findings were reported in Nice, France, at an international meeting of the European Research Organization on Genital Infection and Neoplasia.
There were three cases of genital warts reported for the vaccinated group, compared with 31 cases among the controls. There were no cases of precancerous lesions reported among the vaccinated group and three cases among the control group. HPV-triggered cancers usually take many years to develop fully, and as expected, no cancers were apparent in either study group. No serious side effects were reported.
“To me, the data suggest very strongly that the vaccine will work in men,” Palefsky says. “Policymakers will have to analyze cost-benefit data to tell us who should be vaccinated.”
