Gardasil Protects Against Anal Disease in Young Men Who Have Sex With Men

Nick Mulcahy

March 09, 2010

March 9, 2010 — The human papillomavirus (HPV) quadrivalent vaccine (Gardasil, Merck) is effective in protecting young men who have sex with men (MSM) against some anal lesions that may be associated with the development of anal cancer.

The HPV vaccine was 77.5% efficacious against anal intraepithelial neoplasia (AIN) associated with HPV types 6, 11, 16, and 18, according to Joel M. Palefsky, MD, professor of medicine at the University of California at San Francisco.

The study was conducted in 16- to 24-year-old MSM, and to have been included in the study's per-protocol population analysis (n = 402), they had to have been free of HPV infections from the time of enrollment until a month after the last vaccine dose, noted Dr. Palefsky.

The placebo-controlled study had a median follow-up of 2.5 years.

Dr. Palefsky presented these new data at the European Research Organization on Genital Infection and Neoplasia conference in Monte Carlo, Monaco, on February 20, 2010. Some of the results were subsequently presented at the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices by Merck staff on February 24, 2010.

"It's an extremely positive result," said Dr. Palefsky about the new data.

It's an extremely positive result.

"Potentially, it is an important step forward in protecting the health of men who have sex with men or others who have receptive anal intercourse," he told Medscape Oncology.

In the study's intent-to-treat analysis (n = 551), "all comers" to the MSM study were analyzed, including men with prior exposure to HPV. Gardasil was 51.3% efficacious against AIN associated with HPV types 6, 11, 16, and 18 in this group, said Dr. Palefsky.

Buzz in Gay Community; Women Could Benefit Too

As is the case with Gardasil and cervical cancer, there is no proof to date that the vaccine prevents anal cancer.

However, Dr Palefsky commented, "We believe high-grade AIN is the precursor to anal cancer." He also expects that "prevention of high-grade AIN will likely lead to a reduction in the incidence of anal cancer over time."

In the per-protocol population analysis, efficacy against high-grade AIN (AIN grade ≥2) related to HPV types 6, 11, 16, and 18 was 74.9% (95% confidence interval [CI], 8.8% – 95.4%) in the new study. "The nearly 75% reduction in high-grade lesions is the most hopeful sign that this vaccine will prevent anal cancer," Dr. Palefsky declared.

Anal cancer is a "rare disease," noted Dr. Palefsky. However, the incidence has been steadily increasing by about 2% per year in developed countries, he added. It is a lot more common among MSM.

Men who have sex with men have a 17-times higher rate of anal cancer.

"Men who have sex with men have a 17-times higher rate of anal cancer than the general population," he said.

The vaccination of young MSM has not been thus far beset by the controversy that has embroiled HPV vaccination of girls and young women, suggested Dr. Palefsky. Instead, the MSM study and now the results have been welcomed, he said.

"This is big news for the gay community," said Dr. Palefsky, adding that he had multiple upcoming interviews with gay media and expects "lots of gay media coverage."

This is big news for the gay community.

In the study, 69% of the vaccine group and 64% of the placebo group reported one or more adverse events (AEs), but these were predominantly injection-site AEs, according to press materials from Merck. Merck also indicated that serious AEs were reported rarely and occurred comparably in the vaccine (0.4%) and placebo (0.6%) groups. None were deemed to be vaccine related by the study investigators.

Dr. Palefsky said that the new study provides "more data supporting male vaccination," adding that the vaccine "could protect both boys and girls through 'herd immunity'."

Gardasil is approved in the United States for use in boys and men ages 9 through 26 years for the prevention of genital warts (condylomata acuminata) caused by HPV types 6 and 11.

However, a recent study indicates that vaccinating all boys is not cost-effective, as reported by Medscape Oncology.

The new study results suggest that women who are vaccinated with Gardasil will get a "two-fer," said Dr. Palefsky, referring to protection against both cervical and anal lesions. He also noted that the subject of anal cancer in women is "coming more to light" since the related death of 1970s cultural icon Farrah Fawcett.

Study Design and Details

Previously, Gardasil has been shown to be effective against external genital lesions in men aged 16 to 26 years. The external genital lesions include perianal, perineal, and penile intraepithelial neoplasia and condyloma, said Dr. Palefsky.

The new analysis examined the effect of vaccination on internal anal lesions.

Specifically, Dr. Palefsky and his coinvestigators looked at AIN related to HPV types 6, 11, 16, and 18. However, the study population was not all types of men, but only MSM.

In the analysis, 602 MSM aged 16 to 26 years were randomized to receive vaccine or placebo at enrollment, month 2, and month 6.

Serum was collected at enrollment and at months 7, 24, and 36 for analysis of anti-HPV antibodies.

Subjects underwent detailed anogenital examinations and sampling from the penis, scrotum, and perineal/perianal and anal canal at enrollment, month 7, and 6-month intervals afterward.

Efficacy analyses were performed in a per-protocol population (seronegative at day 1 and DNA negative from day 1 through month 7 to the relevant vaccine HPV type). In summary, young men had to remain uninfected with HPV types 6, 11, 16, or 18 throughout the 6-month vaccination process to be counted in the per-protocol population.

With a median follow-up of 2.5 years, there were 5 cases of AIN among the vaccinated men and 24 cases among the placebo group. The infections in the vaccinated men were related to HPV 6 (n = 3) and HPV 16 (n = 2).

Thus, as noted above, the vaccine efficacy against AIN related to HPV types 6, 11, 16, and 18 in MSM was 77.5% (95% CI, 39.6% – 93.3%).

No anal cancer was seen in either the vaccine or the placebo group, but, with an average follow-up of less than 3 years, it was not expected to be found, Dr. Palefsky added.

The study was funded by Merck. Dr. Palefsky reports research grant support from Merck.

European Research Organization on Genital Infection and Neoplasia 2010 Conference: Abstract SS19-2. Presented February 20, 2010.

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