HPV Vaccine Protects Against Vulvar and Vaginal Cancers

May 18, 2007 — Results suggest that the human papillomavirus (HPV) vaccine (Gardasil; Merck and Co, Whitehouse Station, New Jersey) can protect against vulval and vaginal cancer, although the incidence is rare, but increasing. These data have come soon after other recently published studies confirming the efficacy of the vaccine in protecting against cervical cancer and also showing efficacy in protecting against anogential disease.

The current study, in the May 19 issue of The Lancet, shows that the prophylactic administration of the vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV strains 16 or 18. These results were seen in women who were naive to these HPV strains prior to vaccination, and the maximum effect of the vaccine is expected in girls who are immunized prior to exposure to HPV.

"Vulvar cancer is a rare cancer, but the incidence is rising and there is no screening program for it," study author Marc Steben, MD, from the Institut National de Santé Publique du Québec, told Medscape in an interview. "We're seeing increasing rates, especially in younger women. In younger women, it is usually associated with HPV, but we found that we can prevent up to 90% of all vulval cancer by using this vaccine."

In the current article, the researchers analyzed the data from 3 randomized trials that involved 18,174 women between the ages of 16 to 26 years, who resided in 24 countries across Europe, Asia, and the Americas. The participants were randomly assigned to receive the vaccine or placebo and were followed up for an average of 3 years. The researchers combined an analysis of the 3 trials to assess the vaccine's effect on the rates of high-grade vulval and vaginal lesions associated with HPV types 16 and 18. They also evaluated the overall effect of the vaccine on these lesions whether or not HPV DNA was identified in the lesion.

The vaccine was 100% effective in preventing against vulval intraepithelial neoplasia grade 2-3 (VIN2-3) and vaginal intraepithelial neoplasia grade 2-3 (VaIN2-3) associated with HPV strains 16 and 18 in women without previous exposure to these HPV types and who remained naive throughout the completion of the vaccination program. It was 97% effective in preventing VIN2-3 and VaIN2-3 associated with HPV16 or HPV18 in women who were naive to exposure at the time of first vaccination.

Efficacy was lower in the intent-to-treat population, which included women who may have been previously exposed to HPV16 or HPV18 or who already had a vulval or vaginal HPV-related disease before vaccination. Within this cohort, vaccine efficacy against VIN2-3 or VaIN2-3 associated with either of these 2 HPV types was 71%. The researchers also reported a 49% efficacy rate against all VIN2-3 or VaIN2-3 whether or not HPV DNA was detected in the lesion.

Vulvar cancer is a rare disease, but its treatment can have a significant impact on quality of life, self-image, and sexual functioning, Dr. Steben told Medscape. "The treatment of choice is surgery, and can involve the destruction of very sensitive tissue. Adequate margins are sometimes impossible to achieve and it can be very mutilating."

Vulval intraepithelial neoplasia has a high invasive potential and a high rate of recurrence. Women face a significant risk of developing invasive vulval cancer, even after receiving treatment, Dr. Steben explained.

The true incidence of vaginal intraepithelial neoplasia is unknown, but rates of vulval carcinoma in situ have been rising and increased more than 400% in the United States between 1973 and 2000. During that same time, the incidence of invasive vulval cancer rose by 20%. The overall global rate of vulval carcinoma in situ has been increasing and appears to be primarily associated with HPV16 and HPV18.

Another of the study authors, Diane M. Harper, MD, MPH, from Dartmouth Medical School in Hanover, New Hampshire, told Medscape that more high-grade cases of vulval disease were seen in the study because more women received biopsies. "The fact that we had to combine all Gardasil trials for over 18,000 women-years of history to show 80 cases of VIN2-3 shows that the prevalence is really quite small."

Most cases are still seen in women older than 40 years, and in this study, they were 15 to 26 years old, so the natural history of VIN2-3 lesions in such a young person is not really known, she said. "As the trial data are carried out for more years, we will have an idea of how many cases the placebo and vaccinated arms continue to show."

The duration of protection from the vaccine is still not known, but long-term follow-up is planned in northern Europe, where women will be followed up for at least 10 years, Dr. Harper added.

HPV Vaccine Is Effective but Remains Controversial

Gardasil was approved for use in the United States in June 2006. The published clinical data show that it is effective, but the product has become highly controversial. One of the major points of contention has centered on the proposition in the United States to make the vaccine mandatory for preteen girls, as it is effective only when administered to women who are not infected with HPV.

Many conservative groups oppose making it mandatory, citing fears that it could send a subtle message condoning promiscuous sexual activity. Taking a more scientific view, many experts also point out that new vaccines are generally rolled out gradually, and mandatory use is only endorsed after several years of experience demonstrate that the new products are safe and effective.

Others point out that the overall prevalence of HPV types associated with cervical cancer is relatively low in the United States and that HPV is not a contagious disease like the measles or influenza and is only acquired through sexual activity. Therefore, it is not something that children can catch from each other in the classroom. The vaccine is also expensive, and some public health officials question if the money could be better spent on more pressing issues. Finally, lobbying by the maker of the vaccine to make it mandatory only served to increase the controversy and give the public an unfavorable view of the vaccine.

"The effect of the vaccine does not depend on whether or not the woman has been sexually active," Dr. Harper told Medscape. "What matters is whether or not the woman is currently infected with an HPV infection of the type 6, 11, 16 or 18 at the time of first vaccination. It's very useful for any woman regardless of sexual activity, as long as they are not infected with those virus types at the time of first vaccination."

Merck Research Laboratories, a division of Merck and Co, the maker of the quadrivalent human papillomavirus vaccine, funded this study in its entirety.

Dr. Steben has disclosed receiving consulting fees, advisory board fees, or lecture fees from Digene, Merck Frosst, GlaxoSmithKline, and Roche Diagnostics, and research grants from Merck Frosst and GlaxoSmithKline.

Dr. Harper has disclosed receiving study support for clinical trials, advisory board fees, and speaking fees from Merck and Co.

Lancet. 2007;369:1693-1702.

Source: http://www.medscape.com/viewarticle/556973?src=mp