Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final …
The Lancet, 2009•thelancet.com
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 …
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 …
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 34ˇ9 months (SD 6ˇ4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92ˇ9% (96ˇ1% CI 79ˇ9–98ˇ3) in the primary analysis and 98ˇ1% (88ˇ4–100) 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 30ˇ4% (16ˇ4–42ˇ1) in the TVC and 70ˇ2% (54ˇ7–80ˇ9) in the TVC-naive. Corresponding values against CIN3+ were 33ˇ4% (9ˇ1–51ˇ5) in the TVC and 87ˇ0% (54ˇ9–97ˇ7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54ˇ0% (34ˇ0–68ˇ4; 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.
Funding
GlaxoSmithKline Biologicals.
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