人乳头瘤病毒疫苗预防宫颈癌及其相关感染有效性及安全性的 Meta 分析

摘要

目的：系统评价人乳头瘤病毒（HPV）疫苗预防宫颈癌及 HPV 相关感染的有效性与安全性。方法计算机检索 PubMed、EMBase、Cochrane Library、OVID、中国生物医学文献数据库（CBM）、中国知网、万方数据库，并辅以手工检索相关杂志和纳入研究的参考文献，查找关于 HPV 疫苗预防宫颈癌及 HPV 相关感染的随机对照研究（RCT），检索时限从建库至2014年7月。由2名评价员按照纳入和排除标准独立进行文献筛选、资料提取和质量评价后，采用 RevMan 5.2软件进行 Meta 分析。结果最终纳入23篇 RCT。Meta 分析结果显示，疫苗组宫颈上皮内瘤样病变（CIN）Ⅱ＋发生率、6个月 HPV 持续性感染发生率、12个月 HPV 持续性感染发生率、阴道内皮瘤样变（ VIN）Ⅱ＋/外阴内皮瘤样变（VaIN）Ⅱ＋发生率、外生殖器疣发生率、高危型 HPV（HR - HPV）相关感染与疾病发生率均低于对照组（P ＜0.05）。按照预案规定（PP）人群及意向性分析（ITT）人群，疫苗组 CINⅡ＋发生率、6个月 HPV持续性感染发生率、12个月 HPV 持续性感染发生率、VINⅡ＋/ VaINⅡ＋发生率、外生殖器疣发生率、HR - HPV 相关感染与疾病发生率均低于对照组（P ＜0.05）。疫苗组注射部位相关不良反应发生率高于对照组（P ＜0.05）；疫苗组与对照组系统不良反应发生率、严重不良反应发生率、病死率比较，差异无统计学意义（P ＞0.05）。结论 HPV 疫苗对预防宫颈癌前病变、HPV 持续性感染、HPV 相关外生殖器病变显示了高效的保护效应和交叉保护效果，因此是安全、有效的。然而现有报道尚未证明 HPV 疫苗预防宫颈癌的远期疗效，不能提供 HPV 疫苗预防宫颈癌的直接证据，有待开展更多高质量 RCT 并延长随访时间以进一步验证。%Objective To assess efficacy and safety of prophylactic human papillomavirus( HPV)vaccines in preventing cervical cancer and HPV - related infection,a systematic review and meta - analysis were conducted. Methods Searched in PubMed, EMBase, Cochrane Library, OVID, CBM, CNKI and Wanfang database to identify randomized controlled trials( RCT)on vaccines in preventing cervical cancer and HPV - related infection,and also manually searched relevant magazines and references,the time range for publishing dates of the literatures was from databases establishment to July 2014. According to the inclusion and exclusion criteria,two reviewers independently screened studies,extracted data,and evaluated the quality of studies. The meta - analysis was performed using RevMan software version 5. 2. Results 23 RCTs were included. According to the meta - analysis results,the frequency of CINⅡ + ,VINⅡ + / VaINⅡ + ,6 - months persistent HPV infections,12 - months persistent HPV infections,exophytic genital wart,high - risk HPV - related infections and diseases in vaccine group was significantly lower than that in control group,respectively(P < 0. 05). For plan provisions(PP)group and intention - to - treat( ITT)group,the frequency of CINⅡ + ,6 - months persistent HPV infections,12 - months persistent HPV infections,VINⅡ + / VaINⅡ + ,exophytic genital wart,high - risk HPV - related infections and diseases in vaccine group was significantly lower than that in control group,respectively(P < 0. 05). Prevalence of the injection site - related adverse reactions in vaccine group was significantly higher than that in control group(P < 0. 05). There was no significant difference in prevalences of adverse reaction of the systems,serious adverse events and death between vaccine group and control group(P >0. 05). Conclusion Prophylactic HPV vaccines are safe and effective in preventing cervical precancerous lesions,HPV persistent infections and HPV - related genital lesions,and have cross - protection effect and efficient protective effect. However, according to existing literature,long - term efficacy of HPV vaccines in preventing cervical cancer is not clear,due to the lack of direct evidence of prophylactic HPV vaccines in preventing cervical cancer,more high quality RCT with duration follow - up should be carried out.