Results from an average of 3 years of follow-up from the FUTURE I and FUTURE II clinical trials of Gardasil, a vaccine that protects against the two types of human papillomavirus (HPV) that are responsible for 70 percent of all cases of cervical cancer, have been published in the May 10 New England Journal of Medicine. Earlier data from the FUTURE II trial led to the FDA approval of Gardasil in June of 2006.

The FUTURE I study randomly assigned 5,455 women between the ages of 16 and 24 to receive either a 3-injection course of Gardasil vaccine or placebo. For women who had not previously been exposed to HPV 16 or 18, the efficacy of the vaccine was 100 percent in "preventing vaginal, vulvar, perineal, and perianal intraepithelial lesions or warts associated with the vaccine-type HPV."

In an intention-to-treat analysis, which included women who had previously been exposed to HPV 16 or 18, the vaccine efficacy was 73 percent against all grades of external anogenital or vaginal lesions and 55 percent against all grades of cervical lesions related to those HPV types.

The FUTURE II study randomly assigned 12,167 women between the ages of 15 and 26 to receive either a 3-injection course of Gardasil vaccine or placebo. For women who had not previously been exposed to HPV 16 or 18, the vaccine prevented 98 percent of high-grade cervical intraepithelial neoplasia related to those HPV types.

In an intention-to-treat analysis, which included women who had previously been exposed to HPV 16 or 18, vaccine efficacy was 44 percent against high-grade cervical disease caused by HPV types 16 or 18. As in the FUTURE I trial, "[v]accination did not appear to alter the course of cervical lesions related to HPV 16 or HPV 18 or of infection present at the time of randomization," explained the authors.

The vaccine reduced the rate of all cervical lesions in all patients regardless of prior HPV exposure, including lesions caused by HPV types not included in the vaccine, by 17 percent. "An interim analysis of vaccine trial data submitted to the FDA showed a disproportionate, but not statistically significant, number of cases of grade 2 or 3 cervical intraepithelial neoplasia related to nonvaccine HPV types among vaccinated women," stated Drs. George Sawaya and Karen Smith-McCune from the University of California, San Francisco, in an accompanying editorial. "Updated analyses of data from these ongoing trials will be important to determine the effect of vaccination on rates of preinvasive lesions caused by nonvaccine HPV types."