Medscape Oncology News

By  Nick Mulcahy

March 1, 2011 — Half of all the men participating in a natural history study of human papillomavirus (HPV) were infected with some strain of HPV at some point during study period, according to the results of a new study published online March 1 in the Lancet.

The HPV in Men (HIM) study, led by Anna Giuliano, PhD, from the H. Lee Moffitt Cancer Center in Tampa, Florida, followed 1159 adult males for a median follow-up of 27.5 months.

However, the prevalence of viral types for which there is a prophylactic vaccine is low — 6% for HPV16 and 2% for HPV18 (the 2 oncogenic types), and 7% for HPV6 and 1% for HPV11 (the 2 nononcogenic types).

Data on HPV incidence and clearance from the HIM study have immediate uses, suggests the author of an editorial accompanying the study.

“The HIM data on HPV incidence and clearance should be exploited to elaborate prevention guidance, and to minimize transmission and to aid management and associated concerns for couples,” says editorialist Joseph Monsonego, MD, from the Institute of the Cervix in Paris, France.

Men transmitting HPV to women is especially concerning, writes Dr. Monsonego, because “extrapolation from the HIM data strongly suggests that the natural history of HPV is different in men and women, with high infection and low disease rates in men and low infection and high disease rates in women.”

However, he points out that “the cost–benefit ratio of vaccinating men to protect women from cervical neoplasia has yet to be definitively established.”

Vaccination of men protects them against “lesions associated with the vaccineable HPV types, particularly genital warts and anal intraepithelial neoplasia,” notes Dr. Monsonego.

About the HIM Study

The men participating in the HIM study were from a Brazilian genitourinary clinic, Mexican factories and military, and a Florida university and its local community. Men were eligible for participation if they were 18 to 70 years of age (mean age, 32 years) and were willing to comply with 10 scheduled visits every 6 months for 4 years.

HPV DNA detection with polymerase chain reaction and genotyping were used to test for 37 different HPV types.

For estimates of any or type-specific HPV incidence, only participants who were free of any or a specific HPV type, respectively, at enrollment were included, explain the authors. They found that per year, about 6% of men will acquire a new HPV16 infection, which has been found to be most associated with the development of cancers.

Differences in cumulative incidences were also noted by country. At 1 year, Brazil had the highest incidence of oncogenic infection (P = .0109) and nononcogenic (P < .0001) infection; Mexico had the highest incidence of HPV16 infection (P = .0195).

Clearance Data Are New

Earlier HPV prevalence data from the 4-year HIM study have been previously reported (Cancer Epidemiol Biomarkers Prev.2008;17:2036-2043 and Int J Cancer 2009;124:1251-1257). In the 2008 report, the overall HPV prevalence was 65.2% — higher than the 50% figure in the current report.

What’s new in the current study are data on the timing of infection clearance.

The median time to clearance of HPV16 was about 12 months — nearly twice as long as for other oncogenic HPV types, such as HPV 18 (6.3 months). The finding is similar to what has been reported in women, note the authors.

The median time to clearance of any HPV infection — oncogenic or nononcogenic — was 7.52 months in the study. HPV clearance was defined in HIM as a participant testing negative for HPV on 2 consecutive visits after testing positive.

The study found faster clearance of oncogenic HPV infections in men with increasing age, which “might be related to a higher prevalence of HPV antibodies in older men,” say the authors.

Median time to clearance of infection of any HPV type was “significantly longer” in men 18 to 30 years (9.53 months) than in other age groups, report the authors.

Sexual Behavior Related to Infection

Not surprisingly, sexual behavior is related to infection, the study found.

For instance, men with 50 or more lifetime female sex partners were about 2.5 times as likely to have a worrisome oncogenic strain of HPV as monogamous men with just 1 partner. This same ratio was found in men who had anal sex with at least 3 recent male partners, compared with men with no such recent partners, the study authors report.

Sexual behavior was also related to clearance of infection.

Men reporting 2 to 9, 10 to 49, or at least 50 lifetime female partners, compared with no more than 1, were less likely to clear an oncogenic infection, write the authors.

They conclude that the new data “are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally.”

This is a bit unexpected because nowhere in the study’s introduction, results, or discussion is cost-effectiveness mentioned or explored — until the paper’s concluding sentence.

However, Dr. Giuliano told Medscape Medical News that “cost-effectiveness models take into account the rate at which men acquire infections and the rate at which they clear them. Our data help to provide these needed data.”

Currently, Gardasil, the only HPV vaccine approved for use in males, has its use limited to men 26 years and younger.

To date, 3 studies have found that the vaccination of boys and young men is not cost-effective; 1 study, funded by Merck, the makers of Gardasil, found the opposite. In contrast, vaccinating girls and young women has been found to be cost-effective.

The study was funded by the National Cancer Institute. Dr. Giuliano reports receiving support from Merck, the manufacturer of the HPV vaccine, for the phase 3 Quadrivalent HPV Vaccine Trial Among Men, and serving as a consultant, a member of the Male HPV Advisory Board, and a member of the speaker’s bureau for Merck. Dr. Monsonego reports receiving funding from EUROGIN.

Lancet. Published online March 1, 2011.