US health officials have taken a huge step toward reducing the burden of suffering caused by several gynecologic cancers with the approval of Gardasil, a Merck vaccine against human papillomavirus (HPV). The vaccine protects against two strains of the virus responsible for most cases of cervical as well as some vaginal and vulvar cancers, and against two other strains responsible for most genital warts.

Most oncologists hailed the decision, announced by the US Food and Drug Administration (FDA) in June.

“I don't think you can overestimate the benefit we'll be seeing with the HPV vaccine,” said gynecologic oncologist Robert Ozols, MD, PhD, Senior Vice President of the Medical Science Division at Fox Chase Cancer Center in Philadelphia. “I think this will be a transforming vaccine for millions of women across the world.”

Cervical cancer kills more than 288,000 women worldwide each year, according to the World Health Organization, making it the leading cause of death from cancer in many low-resource countries where widespread screening by cervical cytology is unavailable. In the United States, more than 9,700 new cases of cervical cancer are expected during 2006 and an estimated 3,700 women will die of this disease. According to the US Centers for Disease Control and Prevention (CDC), about 1% of sexually active adults in the United States have genital warts.

The FDA approved the vaccine for girls and women age 9 to 26 years. The Advisory Committee on Immunization Practices, which is part of the CDC, has recommended routine immunization of girls age 11 to 12. The vaccine also may be given to girls as young as 9 at their physician's discretion, and to girls and women age 13 to 26. Merck has ongoing studies evaluating the effectiveness of Gardasil in boys and men age 16 to 26 years, as well as mid-adult women age 24 to 45 years.

Gardasil protects against two strains of HPV, 16 and 18, that are responsible for about 70% of all cervical cancers and a smaller percentage of vaginal and vulvar cancers. It also protects against HPV-6 and HPV-11, which cause about 90% of cases of genital warts.

The CDC estimates that some 6.2 million Americans become infected with genital HPV each year. Most people never even know they have had HPV because they are asymptomatic and their immune systems clear the infection.

When it persists, though, HPV can cause intraepithelial lesions in the cervix, vagina, or vulva. Left untreated, some of these lesions can progress to cancer.

In 4 clinical trials involving nearly 21,000 women and teenage girls, Gardasil was nearly 100% effective in preventing precancerous cervical, vaginal, and vulvar lesions caused by HPV-16 and HPV-18. No cervical lesions related to these HPV types developed among the 8,487 women in the vaccine group, compared with 53 cases among the 8,460 women in the placebo group. Similarly, no high-grade vaginal or vulvar lesions developed in 8,641 vaccinated women compared with 24 cases in 8,667 unvaccinated women.

Gardasil was 99% effective in preventing genital warts caused by HPV-6 and HPV-11, according to Merck. There was just one case among 7,897 women vaccinated with Gardasil compared with 91 cases in 7,899 unvaccinated women.

Approval of the vaccine does not mean women can forget about Pap tests, experts stressed.

“It is critical that girls and young women who receive the vaccine continue to follow screening guidelines,” said Debbie Saslow, PhD, American Cancer Society (ACS) Director of Breast and Gynecologic Cancer.

That's because Gardasil only targets 4 HPV types; there are as many as 40 strains of the virus that can be sexually transmitted, and some of these others can also cause cancer. About 30% of cervical cancers will not be prevented by the vaccine.

Ideally, the vaccine should be given before the onset of sexual activity and thus possible exposure to HPV. Young women who are already sexually active can still benefit, but the likely benefit decreases: The likelihood of exposure to at least one of the 4 HPV types in the vaccine is high within the first 2 years of onset of sexual activity. However, very few women will have been exposed to all four of the HPV types. The vaccine, which is given as 3 injections over a period of 6 months, will protect against only those HPV types to which recipients have not been exposed.

A second HPV vaccine called Cervarix is in development by GlaxoSmithKline. The company has not yet submitted its vaccine to the FDA for approval.

Head-to-head comparisons of the two vaccines have not been done, so it is not clear whether one performs better than the other. Cervarix protects against HPV types 16 and 18, but not 6 and 11, and thus will not prevent genital warts.

Side effects from Gardasil were mild, the FDA said, and included pain or tenderness at the injection site. 

Figure  .

The Merck vaccine Gardasil protects against four types of HPV responsible for most cervical cancers, some vaginal and vulvar cancers, as well as nearly all genital warts.