Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis
Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis
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DOI：
10.1016/s1473-3099(14)71073-4
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发表时间：
2015-05-01
影响因子：
56.3
通讯作者：
Brisson, Marc
中科院分区：
文献类型：
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作者：
Drolet, Melanie;Benard, Elodie;Brisson, Marc
背景 人乳头瘤病毒 (HPV) 疫苗接种计划于 2007 年在全球多个国家首次实施。我们进行了系统回顾和荟萃分析，以评估女性 HPV 疫苗接种计划后的人群水平后果和群体效应，以验证随机对照临床试验中报告的高效是否在现实世界中实现。方法我们检索了 Medline 和 Embase 数据库（2007 年 1 月 1 日至 2014 年 2 月 28 日）和会议摘要，以了解时间趋势研究，分析了疫苗接种前和疫苗接种后期间至少一种 HPV 相关终点的发生率或患病率的变化：HPV 感染、肛门生殖器疣和高度宫颈病变。我们使用随机效应模型来得出汇总相对风险 (RR) 估计值。我们按年龄和性别对所有分析进行分层。我们根据疫苗类型、疫苗接种覆盖率和疫苗接种计划实施年份进行比较研究，进行亚组分析。我们使用 I-2 和 chi(2) 统计数据评估了各项研究的异质性，并进行了趋势分析，以检查 HPV 疫苗接种覆盖率与每项研究效果指标之间的剂量反应关联。结果 我们确定了 20 项符合条件的研究，这些研究均在 9 个高收入国家进行，代表了超过 1.4 亿人年的随访。在女性疫苗接种率至少为 50% 的国家，13-19 岁女孩的 HPV 16 和 18 型感染率在疫苗接种前和疫苗接种后期间显着下降了 68%（RR 0.32，95% CI 0.19-0.52），肛门生殖器疣显着下降了 61%（0.39，0.22-0.71）。该年龄段女孩的 HPV 31、33 和 45 型也显着降低（RR 0.72，95% CI 0.54-0.96），这表明存在交叉保护。此外，20 岁以下男孩 (0.66 [95% CI 0.47-0.91]) 和 20-39 岁女性 (0.68 [95% CI 0.51-0.89]) 的肛门生殖器疣也显着减少，这表明存在群体效应。在女性疫苗接种覆盖率低于 50% 的国家，20 岁以下女孩的 HPV 16 型和 18 型感染（RR 0.50，95% CI 0.34-0.741）和肛门生殖器疣（0.86 [95% CI 0.79-0.94]）显着减少，没有迹象表明存在交叉保护或群体效应。 HPV 疫苗接种计划对人群的长期影响。然而，持续监测对于识别潜在功效减弱或类型替代的任何信号至关重要。
Background Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.Methods We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I-2 and chi(2) statistics and we did trends analysis to examine the dose response association between HPV vaccination coverage and each study effect measure.Findings We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0.32, 95% CI 0.19-0.52) and anogenital warts decreased significantly by 61% (0.39, 0.22-0.71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0.72, 95% CI 0.54-0.96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0.66 [95% CI 0.47-0.91]) and in women 20-39 years of age (0.68 [95% CI 0.51-0.89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0.50, 95% CI 0.34-0.741) and in anogenital warts (0.86 [95% CI 0.79-0.94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.Interpretation Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.