Efficacy of Human Papillomavirus (Hpv)-16/18 As04-Adjuvanted Vaccine against Cervical Infection and Precancer Caused by Oncogenic Hpv Types ( Patricia): Final Analysis of a Double-Blind, Randomised Study in Young Women
Resource
LANCET v.374 n.9686 pp.301-314
Journal
The Lancet
Pages
301-314
Date Issued
2009
Date
2009
Author(s)
Paavonen, J
Naud, P
Salmerón, J
Wheeler, CM
Apter, D
Kitchener, H
Castellsague, X
Teixeira, JC
Skinner, SR
Hedrick, J
Jaisamrarn, U
Limson, G
Garland, S
Szarewski, A
Abstract
Background The 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. Methods Women (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. Findings Mean 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. Interpretation The 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.
SDGs
Other Subjects
3 o desacyl 4' monophosphoryl lipid A; aluminum hydroxide; human papillomavirus 16 18 vaccine; immunological adjuvant; lipid A derivative; unclassified drug; virus DNA; Wart virus vaccine; adolescent; adult; article; cancer incidence; cancer prevention; clinical trial; controlled clinical trial; controlled study; DNA tumor virus; double blind procedure; drug efficacy; drug safety; drug tolerability; female; follow up; human; Human papillomavirus type 16; Human papillomavirus type 18; immunogenicity; normal human; parasite incidence; phase 3 clinical trial; priority journal; randomized controlled trial; seroconversion; unspecified side effect; uterine cervicitis; uterine cervix biopsy; uterine cervix carcinoma in situ; uterine cervix cytology