Joura Elmar A, Leodolter Sepp, Hernandez-Avila Mauricio, Wheeler Cosette M, Perez Gonzalo, Koutsky Laura A, Garland Suzanne M, Harper Diane M, Tang Grace W K, Ferris Daron G, Steben Marc, Jones Ronald W, Bryan Janine, Taddeo Frank J, Bautista Oliver M, Esser Mark T, Sings Heather L, Nelson Micki, Boslego John W, Sattler Carlos, Barr Eliav, Paavonen Jorma
Department of Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria.
Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6.
Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases.
18 174 women (16-26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6-12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population.
The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95% CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18 was 71% (37-88). The vaccine was 49% (18-69) effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain.
Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.
年轻女性的外阴癌和阴道癌通常与人乳头瘤病毒（HPV）感染有关。这些癌症之前会出现高级别外阴上皮内瘤变（VIN2-3）和阴道上皮内瘤变（VaIN2-3）。我们的目的是对三项随机临床试验进行综合分析，以评估预防性四价HPV疫苗对这些疾病发病率的影响。
招募了18174名16至26岁的女性，随机分为在第1天、第2个月和第6个月接受四价HPV6/11/16/18 L1病毒样颗粒疫苗或安慰剂。个体在第1天、第三次给药后1个月以及每隔6至12个月进行详细的肛门生殖器检查，最长持续48个月。对可疑的生殖器病变进行活检，并由一组病理学家进行解读，同时进行疫苗HPV型特异性DNA检测。主要终点是与HPV16或HPV18相关的VIN2-3或VaIN2-3的合并发病率。主要疗效分析在符合方案人群中进行。
平均随访时间为3年。在接种三次疫苗后1个月内对HPV16或HPV18呈阴性的女性中（符合方案人群；疫苗组n = 7811；安慰剂组n = 7785），疫苗对与HPV16或HPV18相关的VIN2-3或VaIN2-3的预防效果为100%（95%可信区间72-100）。在意向性治疗人群（包括18174名在第1天可能已感染HPV16或HPV18的女性）中，疫苗对与HPV16或HPV18相关的VIN2-3或VaIN2-3的疗效为71%（37-88）。疫苗对所有VIN2-3或VaIN2-3的预防效果为49%（18-69），无论病变中是否检测到HPV DNA。最常见的与治疗相关的不良事件是注射部位疼痛。
预防性接种四价HPV疫苗可有效预防接种前对这些类型HPV呈阴性的女性中与HPV16或HPV18感染相关的高级别外阴和阴道病变。随着时间的推移，这种疫苗接种可能会降低HPV相关的外阴癌和阴道癌的发病率。
