Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial
Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial
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DOI：
10.1016/s1470-2045(11)70213-3
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发表时间：
2011-09-01
期刊：
影响因子：
51.1
通讯作者：
Herrero, Rolando
中科院分区：
文献类型：
--
作者：
Kreimer, Aimee R.;Gonzalez, Paula;Herrero, Rolando
背景 肛门癌仍然很少见（每年每 10 万名女性中发病率约为 1.5 例），但许多国家的发病率正在上升。大多数肛门癌病例是由人乳头瘤病毒 (HPV) 16 和 18 感染引起的。我们评估了 AS04 佐剂 HPV 16 和 HPV 18 疫苗对抗 HPV 16、HPV 18 或两者 (HPV 16/18) 肛门感染的功效。 方法 哥斯达黎加女性于 2004 年 6 月 28 日至 2005 年 12 月 21 日期间在一项随机双盲对照试验中进行登记，该试验旨在评估疫苗针对持续性宫颈 HPV 16/18 感染的功效，以及相关癌前病变。符合资格的女性是哥斯达黎加瓜纳卡斯特和蓬塔雷纳斯选定地区的居民，年龄在 18-25 岁，总体健康状况良好，愿意提供知情同意书，并且没有怀孕或哺乳。参与者被随机分配 (1:1) 接受 HPV 疫苗（Cervarix、葛兰素史克、Rixensart、比利时）或对照甲型肝炎疫苗（Havrix、葛兰素史克、Rixensart、比利时的改良制剂）。在入组时、1 个月和 6 个月时接种了 3 剂 0.5 mL 剂量的疫苗。接种疫苗 4 年后，在最后一次盲法研究访视中选择的女性提供了肛门标本，用于评估疫苗针对肛门 HPV 16/18 感染的功效。肛门 HPV 16/18 感染的患病率（报告为疫苗功效）是本文所述研究的主要终点。将同一女性在 4 年访视时针对宫颈 HPV 16/18 感染的疫苗功效用作比较。对子宫颈 HPV 16 和 HPV 18 DNA 均为阴性、入组前 HPV 16 和 HPV 18 血清阴性（未感染 HPV）的一组女性以及提供肛门标本的完整女性组进行了分析。调查人员不知道小组分配情况。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT00128661。 结果 所有参加最终盲法研究访视并同意采集肛门标本的女性均纳入分析（6352 名符合条件的女性中的 4210 名）。在整个队列中，疫苗接种后 4 年一次性测量的针对流行 HPV 16/18 感染的疫苗功效在肛门处（62.0%，95% CI 47.1-73.1）低于子宫颈（76.4%，67.0-83.5；解剖部位相互作用 p 0.031）。在限制性队列中，针对肛门 HPV 16/18 感染的疫苗功效为 83.6% (66.7-92.8)，与针对宫颈 HPV 16/18 感染的疫苗功效 (87.9%, 77.4-94.0) 相似。目前的分析并未解决安全问题。其他安全数据将在稍后发表于另一篇文章中。 解释 AS04 佐剂疫苗可针对肛门 HPV 感染提供强有力的保护，特别是对于在入组时更有可能未感染 HPV 的女性。
Background Anal cancer remains rare (incidence of about 1.5 per 100 000 women yearly), but rates are increasing in many countries. Human papillomavirus (HPV) 16 and 18 infections cause most cases of anal cancer. We assessed efficacy of an AS04-adjuvanted HPV 16 and HPV 18 vaccine against anal infection with HPV 16, HPV 18, or both (HPV 16/18).Methods Women from Costa Rica were registered between June 28, 2004, and Dec 21, 2005, in a randomised double-blind controlled trial that was designed to assess vaccine efficacy against persistent cervical HPV 16/18 infections and associated precancerous lesions. Eligible women were residents of Guanacaste and selected areas of Puntarenas, Costa Rica, age 18-25 years, in good general health, willing to provide informed consent, and were not pregnant or breastfeeding. Participants were randomly assigned (1: 1) to receive an HPV vaccine (Cervarix, GlaxoSmithKline, Rixensart, Belgium) or a control hepatitis A vaccine (modified preparation of Havrix, GlaxoSmithKline, Rixensart, Belgium). Vaccines were administered in three 0.5 mL doses at enrolment, 1 month, and 6 months. Women, selected at the final blinded study visit 4 years after vaccination, provided anal specimens for assessment of vaccine efficacy against anal HPV 16/18 infection. Prevalence of anal HPV 16/18 infections, reported as vaccine efficacy, was the primary endpoint of the study described here. Vaccine efficacy against cervical HPV 16/18 infection in the same women at the 4-year visit was used as a comparator. Analyses were done in a restricted cohort of women who were negative for both cervical HPV 16 and HPV 18 DNA and who were HPV 16 and HPV 18 seronegative before enrolment (HPV naive), and also in the full cohort of women who provided an anal specimen. Investigators were masked to group assignment. This study is registered at ClinicalTrials.gov, number NCT00128661.Findings All women who attended the final blinded study visit and consented to anal specimen collection were included in the analysis (4210 of 6352 eligible women). In the full cohort, vaccine efficacy against prevalent HPV 16/18 infection measured one-time, 4 years post vaccination was lower at the anus (62.0%, 95% CI 47.1-73.1) compared with the cervix (76.4%, 67.0-83.5; p for interaction by anatomical site 0.031). In the restricted cohort, vaccine efficacy against anal HPV 16/18 infection was 83.6% (66.7-92.8), which was similar to vaccine efficacy against cervical HPV 16/18 infection (87.9%, 77.4-94.0). Safety issues were not addressed in the current analysis. Additional safety data will be published later in a separate article.Interpretation The AS04-adjuvanted vaccine affords strong protection against anal HPV infection, particularly among women more likely to be HPV naive at enrolment.