Department of Medicine, University of California at San Francisco, Box 0654, San Francisco, CA 94143, USA.
N Engl J Med. 2011 Oct 27;365(17):1576-85. doi: 10.1056/NEJMoa1010971.
The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men.
In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-to-treat and per-protocol efficacy populations. The rates of adverse events were documented.
Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3% (95% confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5% (95% CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7% (95% CI, -1.1 to 45.6) and 54.9% (95% CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2% (95% CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9% (95% CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4% (95% CI, 43.0 to 71.4) and 94.9% (95% CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported.
Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer. (Funded by Merck and the National Institutes of Health; ClinicalTrials.gov number, NCT00090285.).
女性和男性中，尤其是男男性行为者中，肛门癌的发病率正在上升。肛门癌由人乳头瘤病毒（HPV）感染引起，主要由 HPV 型 16 或 18 引起，之前是高级别肛门上皮内瘤变（2 级或 3 级）。我们研究了四价 HPV 疫苗（qHPV）在男男性行为者中针对 HPV-6、11、16 或 18 感染相关的肛门上皮内瘤变的安全性和有效性。
在一项更大的双盲研究的子研究中，我们随机分配了 602 名年龄在 16 至 26 岁之间的健康男男性行为者，分别接受 qHPV 或安慰剂。主要疗效目标是预防与 HPV-6、11、16 或 18 感染相关的肛门上皮内瘤变或肛门癌。在意向治疗和符合方案疗效人群中进行疗效分析。记录不良事件的发生率。
qHPV 疫苗对与 HPV-6、11、16 或 18 相关的肛门上皮内瘤变的疗效在意向治疗人群中为 50.3%（95%置信区间 [CI]，25.7 至 67.2），在符合方案疗效人群中为 77.5%（95% CI，39.6 至 93.3）；对任何类型 HPV 相关的肛门上皮内瘤变的相应疗效分别为 25.7%（95% CI，-1.1 至 45.6）和 54.9%（95% CI，8.4 至 79.1）。在意向治疗人群中，安慰剂组和疫苗组的肛门上皮内瘤变每 100 人年发生率分别为 17.5 和 13.0，在符合方案疗效人群中分别为 8.9 和 4.0。HPV-6、11、16 或 18 感染相关的 2 级或 3 级肛门上皮内瘤变发生率在意向治疗人群中降低了 54.2%（95% CI，18.0 至 75.3），在符合方案疗效人群中降低了 74.9%（95% CI，8.8 至 95.4）。HPV-6、11、16 或 18 持续肛门感染的风险分别降低了 59.4%（95% CI，43.0 至 71.4）和 94.9%（95% CI，80.4 至 99.4）。未报告疫苗相关的严重不良事件。
qHPV 疫苗的使用降低了男男性行为者肛门上皮内瘤变的发生率，包括 2 级或 3 级病变。该疫苗具有良好的安全性，并可能有助于降低肛门癌的风险。（由默克公司和美国国立卫生研究院资助；临床试验.gov 编号，NCT00090285。）
