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Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials

Villa, L.; Perez, G.; Kjaer, S.; Lehtinen, M.; Paavonen, J.; Munoz, N.; Sigurdsson, K.; Hernandez-Avila, M.; Iversen, O. E. and Thoresen, S., et al. (2007) In The Lancet 369(9576). p.1861-1868
Abstract
Background Cervical cancer and its obligate precursors, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), and adenocarcinona in situ (AIS), are caused by oncogenic human papillomavirus (HPV). In this combined analysis of four clinical trials we assessed the effect of prophylactic HPV vaccination on these diseases. Methods 20 583 women aged 16-26 years were randomised to receive quadrivalent HPV6/11/16/18 vaccine (n=9087), its HPV16 vaccine component (n=1204), or placebo (n=10292). They underwent periodic Papanicolaou testing, with colposcopy or biopsy for detected abnormalities. The primary composite endpoint was the combined incidence of HPV16/18-related CIN2/3, AIS, or cervical cancer. These trials are registered at... (More)
Background Cervical cancer and its obligate precursors, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), and adenocarcinona in situ (AIS), are caused by oncogenic human papillomavirus (HPV). In this combined analysis of four clinical trials we assessed the effect of prophylactic HPV vaccination on these diseases. Methods 20 583 women aged 16-26 years were randomised to receive quadrivalent HPV6/11/16/18 vaccine (n=9087), its HPV16 vaccine component (n=1204), or placebo (n=10292). They underwent periodic Papanicolaou testing, with colposcopy or biopsy for detected abnormalities. The primary composite endpoint was the combined incidence of HPV16/18-related CIN2/3, AIS, or cervical cancer. These trials are registered at ClinicalTrials.gov, numbers NCT00365378, NCT00365716, NCT00092521, and NCT00092534. Findings Mean follow-up was 3.0 years (SD 0.66) after first dose. In women negative for HPV16 or HPV18 infection during the vaccination regimen (n=17129, per protocol), vaccine efficacy was 99% for the primary endpoint (95% Cl 93-100), meeting the statistical criterion for success. In an intention-to-treat analysis of all randomised women (including those who were HPV16/18 naive or HPV16/18-infected at day 1), efficacy was 44% (95% Cl 31-55); all but one case in vaccine recipients occurred in women infected with HPV16 or HPV18 before vaccination. In a second intention-to-treat analysis we noted an 18% reduction (95% CI 7-29) in the overall rate of CIN2/3 or AIS due to any HPV type. Interpretation Administration of HPV vaccine to HPV-naive women, and women who are already sexually active, could substantially reduce the incidence of HPV16/18-related cervical precancers and cervical cancer. (Less)
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The Lancet
volume
369
issue
9576
pages
1861 - 1868
publisher
Elsevier Limited
external identifiers
  • wos:000246911600029
  • scopus:34249654115
ISSN
1474-547X
DOI
10.1016/S0140-6736(07)60852-6
language
English
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yes
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2ef87d9c-51d5-4d07-a1bf-ffdb8aeeb76e (old id 664472)
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2007-12-19 13:03:07
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@article{2ef87d9c-51d5-4d07-a1bf-ffdb8aeeb76e,
  abstract     = {Background Cervical cancer and its obligate precursors, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), and adenocarcinona in situ (AIS), are caused by oncogenic human papillomavirus (HPV). In this combined analysis of four clinical trials we assessed the effect of prophylactic HPV vaccination on these diseases. Methods 20 583 women aged 16-26 years were randomised to receive quadrivalent HPV6/11/16/18 vaccine (n=9087), its HPV16 vaccine component (n=1204), or placebo (n=10292). They underwent periodic Papanicolaou testing, with colposcopy or biopsy for detected abnormalities. The primary composite endpoint was the combined incidence of HPV16/18-related CIN2/3, AIS, or cervical cancer. These trials are registered at ClinicalTrials.gov, numbers NCT00365378, NCT00365716, NCT00092521, and NCT00092534. Findings Mean follow-up was 3.0 years (SD 0.66) after first dose. In women negative for HPV16 or HPV18 infection during the vaccination regimen (n=17129, per protocol), vaccine efficacy was 99% for the primary endpoint (95% Cl 93-100), meeting the statistical criterion for success. In an intention-to-treat analysis of all randomised women (including those who were HPV16/18 naive or HPV16/18-infected at day 1), efficacy was 44% (95% Cl 31-55); all but one case in vaccine recipients occurred in women infected with HPV16 or HPV18 before vaccination. In a second intention-to-treat analysis we noted an 18% reduction (95% CI 7-29) in the overall rate of CIN2/3 or AIS due to any HPV type. Interpretation Administration of HPV vaccine to HPV-naive women, and women who are already sexually active, could substantially reduce the incidence of HPV16/18-related cervical precancers and cervical cancer.},
  author       = {Villa, L. and Perez, G. and Kjaer, S. and Lehtinen, M. and Paavonen, J. and Munoz, N. and Sigurdsson, K. and Hernandez-Avila, M. and Iversen, O. E. and Thoresen, S. and Garcia, P. and Majewski, S. and Tay, E. H. and Bosch, F. X. and Dillner, Joakim and Olsson, S. E. and Ault, K. and Brown, D. and Ferris, D. and Giuliano, A. and Koutsky, L. and Kurman, R. and Myers, E. and Barr, E. and Boslego, J. and Bryan, J. and Esser, M. and Hesley, T. and Lupinacci, L. and Railkar, R. and Sings, H. and Taddeo, F. and Thornton, A.},
  issn         = {1474-547X},
  language     = {eng},
  number       = {9576},
  pages        = {1861--1868},
  publisher    = {Elsevier Limited},
  series       = {The Lancet},
  title        = {Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials},
  url          = {http://dx.doi.org/10.1016/S0140-6736(07)60852-6},
  volume       = {369},
  year         = {2007},
}