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Type: Artigo de periódico
Title: Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years
Author: Romanowski, B
de Borba, PC
Naud, PS
Roteli-Martins, CM
De Carvalho, NS
Teixeira, JC
Aoki, F
Ramjattan, B
Shier, RM
Somani, R
Barbier, S
Blatter, MM
Chambers, C
Ferris, D
Gall, SA
Guerra, FA
Harper, DM
Hedrick, JA
Henry, DC
Korn, AP
Kroll, R
Moscicki, AB
Rosenfeld, WD
Sullivan, BJ
Thoming, CS
Tyring, SK
Wheeler, CM
Dubin, G
Schuind, A
Zahaf, T
Abstract: Background Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. Methods Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with, number NCT00120848. Findings For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% C1 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. Interpretation Our findings show excellent long-term efficacy, high and sustained immunogenicity and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years.
Country: EUA
Editor: Elsevier Science Inc
Rights: fechado
Identifier DOI: 10.1016/S0140-6736(09)61567-1
Date Issue: 2009
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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