Efficacy Of HPV Vaccine Gardasil Among Women Previously Infected With HPV Lower Than Expected, Study Says

The efficacy of Merck's human papillomavirus vaccine Gardasil among women previously infected with the virus is lower than expected, according to a study published in the May 10 issue of the New England Journal of Medicine, the Los Angeles Times reports (Chong/Maugh, Los Angeles Times, 5/10).

Gardasil in previous clinical trials has been shown to be 100% effective in preventing infection with strains 16 and 18, which together cause about 70% of cervical cancer cases, and about 99% effective in preventing HPV strains 6 and 11, which together with strains 16 and 18 cause about 90% of genital wart cases, among women not already infected with these strains. FDA in June 2006 approved Gardasil for sale and marketing to girls and women ages nine to 26, and CDC's Advisory Committee on Immunization Practices later that month voted unanimously to recommend that girls ages 11 and 12 receive the vaccine, which is given in a three-shot series (Kaiser Daily Women's Health Policy Report, 5/1).

For the study, Laura Koutsky, an epidemiologist at the University of Washington, and colleagues studied 12,157 women between ages 15 and 26 (Los Angeles Times, 5/10). The participants were from 13 countries, Reuters reports (Emery, Reuters, 5/10). About 93% of the women enrolled in the study were not virgins when the study began, the USA Today reports (Rubin, USA Today, 5/10). Half of the women and girls were given Gardasil in the recommended three doses over six months and half were given a placebo, the Times reports. All the participants were followed for three years, during which time the researchers recorded any precancerous lesions that developed that had a high risk of progressing into cancer (Los Angeles Times, 5/10).

Before the women received Gardasil or the placebo, they were screened to see whether they had ever been infected by any of the four strains of HPV targeted by the vaccine. The researchers found that less than 1% of the women had been infected with all four strains but 27% had been infected with at least one of the strains (USA Today, 5/10).














The study -- funded by Merck -- found that Gardasil was 98% effective at preventing precancerous lesions of the cervix related to strains 16 and 18 among women previously uninfected with these two strains of the virus. The efficacy of the vaccine was 44% among women previously infected with HPV strains 16 and 18 and was 17% when all precancerous lesions caused by vaccine and nonvaccine types were taken into account, the study found (Carreyrou/Weinstein, Wall Street Journal, 5/10). According to the Times, the data indicate that the vaccine is not "living up" to its original prospects and that 129 women would have to be vaccinated to prevent one precancerous lesion (Los Angeles Times, 5/10).

In a related study, Suzanne Garland of the Royal Women's Hospital in Melbourne, Australia, and colleagues enrolled 5,455 women and girls ages 16 to 24 (Reuters, 5/10). The study found that Gardasil was 100% in preventing cancer, lesions and warts among women who had never been infected with the HPV strains targeted by the vaccine, and efficacy was 20% among women already infected with at least one of the strains (HealthDay News/Forbes, 5/9).

Comments
"It's important that women understand if they're sexually active, there's a chance they won't receive full benefit from the vaccine," Koutsky said (USA Today, 5/10). She added, "The overall message, in my mind, is that among susceptible young women, the vaccine was highly effective in preventing HPV [strains] 16 or 18 precancerous cervical lesions." W. Martin Kast -- an immunologist of the University of Southern California's Keck School of Medicine, who was not involved in the research -- said, "In a three-year follow-up, it is very hard to reach statistical significance in a disease process that takes about a decade to fully develop." He added, "Thus, it is not fair to state that the vaccine is not effective. It will be, but it needs more time to materialize."

Diane Harper of Dartmouth University, who helped design one of the studies, said she is still in favor of giving Gardasil to girls because it is safe and it "protects against the main HPV bad actors," but she said that "neither physicians nor women should be lulled into a false sense of security" by the vaccine. "I don't think this is the gun that is going to take cervical cancer off the map," Harper said (Los Angeles Times, 5/10).

NEJM Editorial, Comments
In an accompanying NEJM editorial, George Sawaya and Karen Smith-McCune, both of the University of California-San Francisco's Department of Obstetrics, Gynecology and Reproductive Sciences, write that the overall efficacy of Gardasil is "modest," adding that a "cautious approach ... may be warranted in light of important unanswered questions about overall vaccine effectiveness, duration of protection and adverse effects that may emerge over time." The authors write that one reason for the limited efficacy might be that other cancer-causing strains of HPV might fill "the biological niche left behind after the elimination of HPV types 16 and 18" (Wall Street Journal, 5/10). Douglas Lowy of the National Cancer Institute, who originally developed Gardasil, said that even if other types of HPV proliferate, there might not be a significant increase in cancers because the other strains are less carcinogenic (Los Angeles Times, 5/10).


The study led by Koutsky and the study led by Garland are available online.

Related NEJM Perspectives, Opinion Pieces
NEJM in the May 10 edition included several perspectives and opinion pieces. Headlines appear below.

"Politics, Parents, and Prophylaxis: Mandating HPV Vaccination in the United States" (Charo, NEJM, 5/10).

"Introducing HPV Vaccine in Developing Countries: Key Challenges and Issues" (Agosti/Goldie, NEJM, 5/10).

"Human Papillomavirus Vaccine: Opportunity and Challenge" (Baden et al., NEJM, 5/10).

"HPV Vaccination: More Answers, More Questions" (Sawaya/Smith-McCune, NEJM, 5/10).

"Human Papillomaviruses in Head and Neck Carcinomas" (Syrj?¤nen, NEJM, 5/10).

"Mandating HPV Vaccination: Private Rights, Public Good" (Stewart, NEJM, 5/10).

Broadcast Coverage

NBC's "Nightly News" on Wednesday included a discussion with Nancy Snyderman, NBC News chief medical editor, about the studies and other topics (Williams, "Nightly News," NBC, 5/9). Video of the segment is available online.


NPR's "All Things Considered" on Wednesday reported on the studies. The segment includes comments from Sawaya; Koutsky; and Connie Trimble, an ob-gyn and cervical cancer specialist at Johns Hopkins University (Neighmond, "All Things Considered," NPR, 5/9). Audio and a partial transcript of the segment are available online.

"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.



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