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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 05/22/2007

New Data from HPV Vaccine Trials Available

Adapted from the NCI Cancer Bulletin.

Results from an average of three 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, 2007, 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 three-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." (See the journal abstract).

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. (An intention-to-treat analysis is one in which all the participants in a trial are analyzed according to the intervention to which they were allocated, whether they received it or not. Such analyses mirror the noncompliance and treatment changes that are likely to occur when the intervention is used in everyday practice.)

The FUTURE II study randomly assigned 12,167 women between the ages of 15 and 26 to receive either a three-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. (See the journal abstract.)

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."