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Efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis

In young women free of the two target virus types at vaccination, the bivalent vaccine prevented 93 percent of high-grade cervical precancers caused by those types, and it also protected against some related virus types it was not designed for.

Final event-driven analysis of PATRICIA (NCT00122681). Women aged 15 to 25 were vaccinated at months 0, 1 and 6 with the HPV-16/18 AS04-adjuvanted vaccine or a hepatitis A control. Analyses were done in the according-to-protocol cohort for efficacy (vaccine 8,093, control 8,069), the total vaccinated cohort (9,319 and 9,325) and the TVC-naive cohort of women with no evidence of oncogenic HPV infection at baseline (5,822 and 5,819). The primary endpoint was efficacy against CIN2+ associated with HPV-16 or HPV-18 in women seronegative at baseline and DNA negative at baseline and month 6 for the corresponding type.

Mean follow-up was 34.9 months after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9 percent (96.1 percent CI 79.9 to 98.3) in the primary analysis and 98.1 percent (88.4 to 100) with probable causality assigned in lesions with several oncogenic types. Efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4 percent in the total vaccinated cohort and 70.2 percent in the TVC-naive cohort; against CIN3+ it was 33.4 percent and 87.0 percent. Efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0 percent, with individual cross-protection against HPV-31, HPV-33 and HPV-45.

Randomised controlled trialChanged practice18,644 participants

Authors

Paavonen J, Naud P, Salmerón J, et al.

Published

The Lancet, 2009

Full text

doi:10.1016/S0140-6736(09)61248-4 PubMed 19586656

Findings

Vaccine efficacy against CIN2+ associated with HPV-16/18: 92.9 percent (96.1 percent CI 79.9 to 98.3) in the primary analysis; 98.1 percent with HPV-type causality assigned.
Efficacy against CIN2+ irrespective of HPV type: 30.4 percent in the total vaccinated cohort and 70.2 percent in women HPV-naive at baseline; against CIN3+, 33.4 and 87.0 percent.
Cross-protection: 54.0 percent efficacy against CIN2+ associated with 12 non-vaccine oncogenic types, with individual protection against HPV-31, HPV-33 and HPV-45.

What it means

This is the efficacy evidence behind the EU (2007) and US (2009) approvals of Cervarix. The gap between near-complete type-specific protection and the 30 percent overall effect in the whole cohort is the argument for vaccinating before sexual debut, where the effect was 70 percent.

Caveats

The 96.1 percent confidence level reflects the alpha spent at the interim analysis.
Efficacy against cervical cancer itself is inferred from precancer endpoints; cancer endpoints came later from registry linkage studies.
GSK withdrew Cervarix from the US market in 2016 for commercial reasons; it remains WHO-prequalified.