First cancer vaccine approved for women

July 24, 2006

Women now have the option of being immunized against cervical cancer following approval of Merck's Gardasil. Roughly 6.2 million Americans become infected with genital human papillomavirus (HPV) each year, and more than 50% of all sexually active persons become infected at some point. HPV is the most common sexually transmitted infection in the United States. While the body's immune system clears the virus in most women, some go on to develop cervical abnormalities that can lead to cancer. Cervical cancer is the second most common cause of cancer death in women, with roughly 470,000 new cases and 233,000 deaths occurring each year worldwide.

Gardasil is a quadrivalent vaccine prepared from HPV proteins. It provides 100% protection against HPV types 16 and 18 (the virus types that cause approximately 70% of cervical cancers) and 99% protection against HPV types 6 and 11 (these types cause approximately 90% of genital warts). It is approved for use in women and girls between the ages of nine and 26 years for the prevention of cervical cancer, genital warts (condyloma acuminata), and precancerous lesions, including: cervical adenocarcinoma in situ (AIS), cervical intraepithelial neoplasia (CIN) grades 2 and 3, vulvar intraepithelial neoplasia (VIN) grades 2 and 3, vaginal intraepithelial neoplasia (VaIN) grades 2 and 3, and CIN grade 1.

Approval of Gardasil was based on four placebo-controlled, double-blind, randomized phase II and III clinical studies evaluating 20,541 women aged 16-26 years. It prevented 100% of HPV 16-and 18-related cervical, vulvar, and vaginal precancers, 95% of HPV 6-, 11-, 16-, or 18-related low-grade CIN, and 99% of HPV 6-or 11-related cases of genital warts during a five-year follow-up. While the study was not conducted long enough for cervical cancer to develop, prevention of precancerous cervical lesions is believed to prevent subsequent cancer. Merck also evaluated immune responses and titer levels in vaccinated girls. Outcomes were similar, and the FDA approved the vaccine for use also in adolescent females ages nine to 15 years.

Some gynecologists disagree about the proposed age for vaccinating young girls. Diane Harper, M.D., a primary investigator for the HPV vaccine clinical trials at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., believes the ideal age for routine HPV vaccination should be 15 years. "We see a peak of HPV prevalence among 15-to 25-year-olds, with the first peak of cancer in the 30s to 40s. Let's not set girls up to fail by vaccinating them too early," she said.

Monica Skomo, Pharm.D., assistant professor at Duquesne's school of pharmacy in Pittsburgh, is excited about the vaccine. "It is the first vaccine that prevents cancer. And the proposed target population, vaccinating young girls, is interesting." But, she cautioned, "women still have to have PAP smears even if they have been vaccinated and are presumed to be protected. It is a beneficial vaccine, but it will take a while to see the benefits."