TY - JOUR
T1 - Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against certivcla infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women
AU - Paavonen, J.
AU - Naud, P.
AU - Salmeron, J.
AU - Wheeler, C.M.
AU - Chow, S-N.
AU - Apter, D.
AU - Kitchener, H.
AU - Castellsague, X.
AU - Teixeira, J.C.
AU - Skinner, Susan
AU - Hedrick, J.
AU - Jaisamram, U.
AU - Limson, G.
AU - Garland S, [No Value]
AU - Szarewski, A.
AU - Romanowski, B.
AU - Aoki, F.Y.
AU - Schwarz, T.F.
AU - Poppe, W.A.
AU - Bosch, F.X.
AU - Jenkins, D.
AU - Hardt, K.
AU - Zahaf, T.
AU - Descamps, D.
AU - Struyf, F.
AU - Lehtinen, M.
AU - Dubin, G.
PY - 2009
Y1 - 2009
N2 - BackgroundThe human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis.MethodsWomen (15—25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681.FindingsMean follow-up was 34·9 months (SD 6·4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92·9% (96·1% CI 79·9—98·3) in the primary analysis and 98·1% (88·4—100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30·4% (16·4—42·1) in the TVC and 70·2% (54·7—80·9) in the TVC-naive. Corresponding values against CIN3+ were 33·4% (9·1—51·5) in the TVC and 87·0% (54·9—97·7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54·0% (34·0—68·4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC.InterpretationThe HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes.FundingGlaxoSmithKline Biologicals.
AB - BackgroundThe human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis.MethodsWomen (15—25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681.FindingsMean follow-up was 34·9 months (SD 6·4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92·9% (96·1% CI 79·9—98·3) in the primary analysis and 98·1% (88·4—100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30·4% (16·4—42·1) in the TVC and 70·2% (54·7—80·9) in the TVC-naive. Corresponding values against CIN3+ were 33·4% (9·1—51·5) in the TVC and 87·0% (54·9—97·7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54·0% (34·0—68·4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC.InterpretationThe HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes.FundingGlaxoSmithKline Biologicals.
UR - https://www.scopus.com/pages/publications/67651049056
U2 - 10.1016/S0140-6736(09)61248-4
DO - 10.1016/S0140-6736(09)61248-4
M3 - Article
SN - 0140-6736
VL - 374
SP - 301
EP - 313
JO - The Lancet
JF - The Lancet
IS - 9686
ER -
