Study casts new doubts on HPV vaccine

According to a study funded by Merck and published on May 10 in the New England Journal of Medicine, Gardasil, the company's human papillomavirus (HPV) vaccine, may be less effective at preventing cervical cancer than previously thought. Cervical cancer kills about 3,900 US women each year. About 20 strains of HPV are known, some of which may lead to cervical cancer. Gardasil targets HPV strains 16 and 18, which are said to be implicated in 70 percent of cervical cancers, and two other strains that are said to produce the majority of genital warts. For the study, researchers monitored 12,157 women between ages 15 and 26. They were screened to see whether they were infected with any of the four targeted HPV strains. The researchers found that 27 percent had been infected with at least one of the four strains. Half were then given Gardasil in the recommended three doses over six months and half were given a placebo. For three years researchers recorded any precancerous lesions that developed that had a high risk of progressing into cancer. Among women who had not previously been exposed to types 16 and 18, the vaccine reduced the risk of precancerous lesions caused by those two strains by 98 percent. When the researchers included all the women enrolled in the study, the vaccine reduced the risk of lesions caused by types 16 and 18 by 44 percent. The number of women who were previously infected by strains 16 and 18 was not large enough to account for this low rate of protection. When Koutsky and her colleagues considered lesions caused by all strains of the virus, Gardasil reduced the risk by only 17 percent. Because researchers had previously believed that 50 percent of all serious precancerous lesions were caused by types 16 and 18, this rate of protection seemed inexplicably low. In an accompanying editorial, Dr. George F. Sawaya and Dr. Karen Smith-McCune, both of the University of California-San Francisco's Department of Obstetrics, Gynecology and Reproductive Sciences, wrote that one reason for the limited efficacy might be that other cancer-causing strains of HPV are filling "the biological niche left behind after the elimination of HPV types 16 and 18." Sawaya and Smith-McCune said 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." Gardasil was approved by the Food and Drug Administration last June. The Centers for Disease Control and Prevention recommended that all girls and women ages 11 to 26 receive it. The American Cancer Society seconded the recommendation, although it concluded that there was "insufficient evidence" of benefit among women ages 19 to 26 because so many had already been exposed to HPV. Gardasil costs about $360, not including the cost of three office visits. Merck has so far distributed over 4 million doses. At least 24 state legislatures have introduced bills calling for mandatory vaccination of girls in their early teens or younger. Virginia recently became the first state to pass a law requiring Gardasil for girls entering the sixth grade, unless a parent refuses. In New Hampshire, health officials say they have found an optimal method to encourage Gardasil's use: making it voluntary and giving it free to girls and young women ages 11 to 18. At least two other states, South Dakota and Washington, are following New Hampshire's lead.