Harper Diane M, Franco Eduardo L, Wheeler Cosette M, Moscicki Anna-Barbara, Romanowski Barbara, Roteli-Martins Cecilia M, Jenkins David, Schuind Anne, Costa Clemens Sue Ann, Dubin Gary
Department of Obstetrics and Gynecology, Norris Cotton Cancer Center, Dartmouth Medical School, Rubin 880, One Medical Center Drive, Lebanon, NH 03756, USA.
Lancet. 2006 Apr 15;367(9518):1247-55. doi: 10.1016/S0140-6736(06)68439-0.
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.
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.
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.
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.
有效接种针对人乳头瘤病毒16型（HPV 16）和人乳头瘤病毒18型（HPV 18）的疫苗以预防宫颈癌，将需要对感染和癌前病变提供高水平的持续保护。我们的目的是评估二价HPV-16/18 L1病毒样颗粒AS04疫苗针对HPV 16和HPV 18的新发感染和持续感染及其相关细胞学和组织学结果的长期疗效、免疫原性和安全性。
我们对2004年报道的多中心、双盲、随机、安慰剂对照试验进行了随访研究。纳入最初接受三剂二价HPV-16/18病毒样颗粒AS04疫苗（0.5 mL；n = 393）或安慰剂（n = 383）的女性。我们使用宫颈样本评估HPV DNA，并每年进行宫颈细胞学评估。我们还研究了疫苗的长期免疫原性和安全性。
在延长的随访期内，HPV-16/18抗体的血清阳性率维持在98%以上。我们注意到疫苗对HPV-16和HPV-18终点具有显著疗效：新发感染，96.9%（95%CI 81.3-99.9）；持续感染：6个月定义，94.3（63.2-99.9）；12个月定义，100%（33.6-100）。在初始疗效和延长随访研究的综合分析中，疫苗对与疫苗型别相关的宫颈上皮内瘤变（CIN）病变的疗效为100%（42.4-100）。我们注意到疫苗对细胞组织学结果具有广泛的保护作用，超出了对HPV 16/18预期的保护范围，并且对HPV 45和HPV 31的新发感染也有保护作用。该疫苗具有良好的长期安全性。
长达4.5年，HPV-16/18 L1病毒样颗粒AS04疫苗具有高度免疫原性且安全，并能诱导对HPV-16/18感染及相关宫颈病变的高度保护。也有交叉保护的证据。
