Sustained efficacy up to 4·5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial

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• 作者：Diane M Harper ; Eduardo L Franco ; Cosette M Wheeler ; Anna-Barbara Moscicki ; Barbara Romanowski ; Cecilia M Roteli-Martins ; David Jenkins ; Anne Schuind ; Sue Ann Costa Clemens ; Gary Dubin and on behalf o
• 刊名：The Lancet
• 出版年：2006
• 出版时间：15 April 2006-21 April 2006
• 年：2006
• 卷：367
• 期：9518
• 页码：1247-1255
• 全文大小：134 K

文摘

Summary

Background

Effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions. Our aim was to assess the long-term efficacy, immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine against incident and persistent infection with HPV 16 and HPV 18 and their associated cytological and histological outcomes.

Methods

We did a follow-up study of our multicentre, double-blind, randomised, placebo-controlled trial reported in 2004. We included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine (0·5 mL; n=393) or placebo (n=383). We assessed HPV DNA, using cervical samples, and did yearly cervical cytology assessments. We also studied the long-term immunogenicity and safety of the vaccine.

Findings

More than 98 % seropositivity was maintained for HPV-16/18 antibodies during the extended follow-up phase. We noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints: incident infection, 96·9 % (95 % CI 81·3–99·9); persistent infection: 6 month definition, 94·3 (63·2–99·9); 12 month definition, 100 % (33·6–100). In a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100 % (42·4–100) against cervical intraepithelial neoplasia (CIN) lesions associated with vaccine types. We noted broad protection against cytohistological outcomes beyond that anticipated for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31. The vaccine has a good long-term safety profile.

Interpretation

Up to 4·5 years, the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe, and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions. There is also evidence of cross protection.