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 Gale Ferris, Laura A. Koutsky & 12 others Robert 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

Research output: Contribution to journalArticle

1498 Citations (Scopus)

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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Papillomavirus Vaccines
Human papillomavirus 16
Human papillomavirus 18
Vaccines
Human papillomavirus 11
Human papillomavirus 6
Placebos
Cervical Intraepithelial Neoplasia
Confidence Intervals
Uterine Cervical Neoplasms
Population
Primary Prevention
Random Allocation
Infection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Villa, L. L., Perez, G., Kjaer, S. K., Paavonen, J., Lehtinen, M., Muñoz, N., ... 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

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

In: New England Journal of Medicine, Vol. 356, No. 19, 10.05.2007, p. 1915-1927.

Research output: Contribution to journalArticle

Villa, LL, Perez, G, Kjaer, SK, Paavonen, J, Lehtinen, M, Muñoz, N, Sigurdsson, K, Hernandez-Avila, M, Skjeldestad, FE, Thoresen, S, García, P, Majewski, S, Dillner, J, Olsson, SE, Eng, HT, Bosch, FX, Ault, KA, Brown, DR, Ferris, DG, Koutsky, LA, Kurman, RJ, Myers, ER, Barr, E, Boslego, J, Bryan, J, Esser, MT, Gause, CK, Hesley, TM, Lupinacci, LC, Sings, HL, Taddeo, FJ & Thornton, AR 2007, 'Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions', New England Journal of Medicine, vol. 356, no. 19, pp. 1915-1927. https://doi.org/10.1056/NEJMoa061741
Villa LL, Perez G, Kjaer SK, Paavonen J, Lehtinen M, Muñoz N et al. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. New England Journal of Medicine. 2007 May 10;356(19):1915-1927. https://doi.org/10.1056/NEJMoa061741
Villa, Luisa L. ; Perez, Gonzalo ; Kjaer, Susanne K. ; Paavonen, Jorma ; Lehtinen, Matti ; Muñoz, Nubia ; Sigurdsson, Kristján ; Hernandez-Avila, Mauricio ; Skjeldestad, Finn Egil ; Thoresen, Steinar ; García, Patricia ; Majewski, Slawomir ; Dillner, Joakim ; Olsson, Sven Eric ; Eng, Hseon Tay ; Bosch, F. Xavier ; Ault, Kevin A. ; Brown, Darron R. ; Ferris, Daron Gale ; Koutsky, Laura A. ; Kurman, Robert J. ; Myers, Evan R. ; Barr, Eliav ; Boslego, John ; Bryan, Janine ; Esser, Mark T. ; Gause, Christine K. ; Hesley, Teresa M. ; Lupinacci, Lisa C. ; Sings, Heather L. ; Taddeo, Frank J. ; Thornton, Annemarie R. / Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. In: New England Journal of Medicine. 2007 ; Vol. 356, No. 19. pp. 1915-1927.
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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.",
author = "Villa, {Luisa L.} and Gonzalo Perez and Kjaer, {Susanne K.} and Jorma Paavonen and Matti Lehtinen and Nubia Mu{\~n}oz and Kristj{\'a}n Sigurdsson and Mauricio Hernandez-Avila and Skjeldestad, {Finn Egil} and Steinar Thoresen and Patricia Garc{\'i}a and Slawomir Majewski and Joakim Dillner and Olsson, {Sven Eric} and Eng, {Hseon Tay} and Bosch, {F. Xavier} and Ault, {Kevin A.} and Brown, {Darron R.} and Ferris, {Daron Gale} and Koutsky, {Laura A.} and Kurman, {Robert J.} and Myers, {Evan R.} and Eliav Barr and John Boslego and Janine Bryan and Esser, {Mark T.} and Gause, {Christine K.} and Hesley, {Teresa M.} and Lupinacci, {Lisa C.} and Sings, {Heather L.} and Taddeo, {Frank J.} and Thornton, {Annemarie R.}",
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T1 - Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions

AU - Villa, Luisa L.

AU - Perez, Gonzalo

AU - Kjaer, Susanne K.

AU - Paavonen, Jorma

AU - Lehtinen, Matti

AU - Muñoz, Nubia

AU - Sigurdsson, Kristján

AU - Hernandez-Avila, Mauricio

AU - Skjeldestad, Finn Egil

AU - Thoresen, Steinar

AU - García, Patricia

AU - Majewski, Slawomir

AU - Dillner, Joakim

AU - Olsson, Sven Eric

AU - Eng, Hseon Tay

AU - Bosch, F. Xavier

AU - Ault, Kevin A.

AU - Brown, Darron R.

AU - Ferris, Daron Gale

AU - Koutsky, Laura A.

AU - Kurman, Robert J.

AU - Myers, Evan R.

AU - Barr, Eliav

AU - Boslego, John

AU - Bryan, Janine

AU - Esser, Mark T.

AU - Gause, Christine K.

AU - Hesley, Teresa M.

AU - Lupinacci, Lisa C.

AU - Sings, Heather L.

AU - Taddeo, Frank J.

AU - Thornton, Annemarie R.

PY - 2007/5/10

Y1 - 2007/5/10

N2 - 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.

AB - 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.

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