New studies on Merck & Co’s much-vaunted cervical vaccine Gardasil have confirmed the efficacy of the treatment but have also raised doubts about its long-term effectiveness and the value of across-the-board vaccination for young women.
Follow-up data from two Phase III studies (FUTURE I and II) published in the New England Journal of Medicine indicates that Gardasil is highly effective for at least three years at preventing precancerous lesions caused by human papillomavirus types 16 or 18 and cervical, vaginal and vulvar diseases caused by HPV types 6, 11, 16, or 18.
In FUTURE I, which involved 5,455 women, Gardasil was shown to provide 100% protection against cervical, vaginal and vulvar diseases caused by HPV types 6, 11, 16, or 18. In the follow-up period, there were no cases of cervical or precancerous lesions due to the four HPV types among those who received the vaccine, compared to 65 cases found in the placebo group.
In the FUTURE II trial, 12,167 women who were not infected with either of HPV types 16 or 18 at the start of the study, were randomised to receive a three-dose regimen of either Gardasil over a six-month period, or placebo. After three years, the vaccine prevented 98% of precancerous lesions caused by the two HPV types, which together are associated with about 70% of cervical cancers.
However, the study also found that Gardasil efficacy for preventing precancers and non-invasive cancers in the overall patient population, which included women already infected with any type of HPV, was only 17%. In an editorial in the NEJM, Drs George Sawaya and Karen Smith-McCune of the University of California, San Francisco, said that while Gardasil appears to be safe and effective, "a cautious approach may be warranted" because of questions that still remain about the drug's long-term effectiveness and potential for adverse effects that could emerge over time.
"Until we have the data, I view the situation as an ongoing experimental trial. The ultimate safety of the vaccine is unknown and it's going to be decades before we know anything,'' wrote the doctors, adding that "the recommendation for widespread vaccination of women after they become sexually active may need to be rethought".
Mandatory vaccination has caused a great deal of controversy and this data could result in this option becoming less of a matter of urgency. In the USA, the tide seems to have already changed after Texas Governor Rick Perry conceded defeat in his effort to require that pre-teenage girls be vaccinated.
Last February, Gov Perry announced mandatory HPV vaccination programmes for girls aged 11 and 12 and employed an executive order to do so. However the state’s legislature passed a bill last month contravening the order by preventing the vaccination programme for at least four years.
The governor said he will not veto the legislation, but criticised the decision, saying that the legislature has “sent me a bill that will ensure three-quarters of our young women will be susceptible to a virus that not only kills hundreds each year, but causes great discomfort and harm to thousands more.