Background Human papillomavirus types 16 (HPV-16) and 18 (HPV-18)cause approximately 70% of cervical cancers worldwide. A phase3 trial was conducted to evaluate a quadrivalent vaccine againstHPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the preventionof high-grade cervical lesions associated with HPV-16 and HPV-18.
Methods In this randomized, double-blind trial, we assigned12,167 women between the ages of 15 and 26 years to receivethree doses of either HPV-6/11/16/18 vaccine or placebo, administeredat day 1, month 2, and month 6. The primary analysis was performedfor a per-protocol susceptible population that included 5305women in the vaccine group and 5260 in the placebo group whohad no virologic evidence of infection with HPV-16 or HPV-18through 1 month after the third dose (month 7). The primarycomposite end point was cervical intraepithelial neoplasia grade2 or 3, adenocarcinoma in situ, or cervical cancer related toHPV-16 or HPV-18.
Results Subjects were followed for an average of 3 years afterreceiving the first dose of vaccine or placebo. Vaccine efficacyfor the prevention of the primary composite end point was 98%(95.89% confidence interval [CI], 86 to 100) in the per-protocolsusceptible population and 44% (95% CI, 26 to 58) in an intention-to-treatpopulation of all women who had undergone randomization (thosewith or without previous infection). The estimated vaccine efficacyagainst all high-grade cervical lesions, regardless of causalHPV type, in this intention-to-treat population was 17% (95%CI, 1 to 31).
Conclusions In young women who had not been previously infectedwith HPV-16 or HPV-18, those in the vaccine group had a significantlylower occurrence of high-grade cervical intraepithelial neoplasiarelated to HPV-16 or HPV-18 than did those in the placebo group.(ClinicalTrials.gov number, NCT00092534
[ClinicalTrials.gov]
.)
Source Information
Address reprint requests to Dr. Laura A. Koutsky at the Department of Epidemiology, University of Washington, Box 359933, Lake Union Place, Suite 300, 1914 N. 34th St., Seattle, WA 98103, or at kouts{at}u.washington.edu.
Human Papillomavirus Vaccine
Miller N. B., Raychaudhuri G., Toerner J. G., Suba E. J., Raab S. S., the Viet/American Cervical Cancer Prevention Project , Garland S. G., Koutsky L. A., Sawaya G. F., Smith-McCune K., Agosti J. M., Goldie S. J.
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N Engl J Med 2007;
357:1154-1156, Sep 13, 2007.
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