Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions

Luisa L. Villa, Gonzalo Perez, Susanne K. Kjaer, Jorma Paavonen, Matti Lehtinen, Nubia Muñoz, Kristján Sigurdsson, Mauricio Hernandez-Avila, Finn Egil Skjeldestad, Steinar Thoresen, Patricia García, Slawomir Majewski, Joakim Dillner, Sven Eric Olsson, Hseon Tay Eng, F. Xavier Bosch, Kevin A. Ault, Darron R. Brown, Daron G. Ferris, Laura A. KoutskyRobert J. Kurman, Evan R. Myers, Eliav Barr, John Boslego, Janine Bryan, Mark T. Esser, Christine K. Gause, Teresa M. Hesley, Lisa C. Lupinacci, Heather L. Sings, Frank J. Taddeo, Annemarie R. Thornton

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Abstract

BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.

Original languageEnglish (US)
Pages (from-to)1915-1927
Number of pages13
JournalNew England Journal of Medicine
Volume356
Issue number19
DOIs
StatePublished - May 10 2007

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ASJC Scopus subject areas

  • Medicine(all)

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Villa, L. L., Perez, G., Kjaer, S. K., Paavonen, J., Lehtinen, M., Muñoz, N., Sigurdsson, K., Hernandez-Avila, M., Skjeldestad, F. E., Thoresen, S., García, P., Majewski, S., Dillner, J., Olsson, S. E., Eng, H. T., Bosch, F. X., Ault, K. A., Brown, D. R., Ferris, D. G., ... Thornton, A. R. (2007). Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. New England Journal of Medicine, 356(19), 1915-1927. https://doi.org/10.1056/NEJMoa061741