HPV多价疫苗接种效果的Meta分析

Meta-Analysis of the Efficacy of Multivalent HPV Vaccines

摘要: 目的：对已上市的几种宫颈癌疫苗接种后的发病率进行Meta分析，以观察其接种效果。方法：计算机检索PubMed、CNKI、万方、维普等文献数据库，在此基础上再行人工复检找到相关文献，检索的时间跨度为2012年1月至2022年3月。最终纳入采用随机对照试验(RCT)的HPV二价疫苗(Cervarix^TM)、国产疫苗(馨可宁^TM)、HPV四价疫苗(Gardasil^TM)和HPV九价疫苗(Gardasil9^TM)文献。将纳入的文献根据Jadad量表进行质量评价，从符合要求的文献中进行数据提取并使用RevMan v5.3软件进行Meta分析。结果：依照纳入标准：二价以及四价疫苗的接种对象均为年龄9~45岁的女性人群，九价疫苗接种对象的年龄均为16~26岁的女性人群，接种方式均为肌肉注射，接种程序均为0-1-6 (注射第一针后隔一个月注射第二针，从第一针算起第六个月注射第三针)或0-2-6。共纳入符合要求的文献9篇，Meta分析结果显示：所有接种了HPV疫苗后的HPV感染人数均降低[95%CI (0.05, 0.21), OR = 0.10, P < 0.00001]；接种了四价HPV疫苗后相关HPV CIN+发病人数降低[95%CI (0.07, 0.10), OR = 0.08, P < 0.00001]；接种九价HPV疫苗后，与HPV 31型、33型、45型、52型或58型相关的宫颈、外阴和阴道疾病的发病人数显著降低[95%CI (0.01, 0.07), OR = 0.03, P < 0.00001]，差异显著，均有统计学意义。结论：接种HPV疫苗后较未接种疫苗的人群有更强的免疫性，发病人数降低90%；接种四价疫苗后CIN+的发病人数较未接种四价疫苗的发病人数明显降低，CIN+人数只有未接种四价疫苗的8%，对于预防CIN+有明显的保护效果；接种了九价HPV疫苗较接种四价疫苗发生HPV 31、33、45、52、58型相关宫颈、外阴和阴道疾病人数减少了97%，表明九价疫苗相比四价疫苗预防了更多型别的HPV病毒。

Abstract: Objective: To conduct a Meta-analysis of the incidence rate of several cervical cancer vaccines currently available on the market after vaccination and observe the effect of vaccination. Methods: PubMed, CNKI, Wanfang, VIP and other literature databases were searched by computer. On this basis, the relevant literature was re-examined manually. The search time span was from January 2012 to March 2022. Finally, the literature of HPV bivalent vaccine (Cervarix^TM), domestic vaccine (Xinkening^TM), HPV tetravalent vaccine (Gardasil^TM) and HPV nine-valent vaccine (Gardasil9^TM) using randomized controlled trial (RCT) was included. The quality of the included literature was evaluated according to the Jadad scale, and the data were extracted from the qualified literature and RevMan v5.3 software for Meta-analysis. Results: According to the inclusion criteria: the vaccinated objects of bivalent and tetravalent vaccines were women aged 9~45, and the vaccinated objects of nine-valent vaccine were women aged 16~26. The vaccination methods were intramuscular injection, and the vaccination procedures were 0-1-6 (the second injection was injected every one month after the first injection, and the third injection was injected in the sixth month from the first injection) or 0-2-6. A total of 9 studies meeting the requirements were included. The results of Meta-analysis showed that the number of HPV infections after HPV vaccination decreased [95%Cl (0.05, 0.21), OR = 0.10, P < 0.00001]; After vaccination with tetravalent HPV vaccine, the incidence of related HPV CIN+ decreased [95%Cl (0.07, 0.10), OR = 0.08, P < 0.00001]; After vaccination with nine-valent HPV vaccine, the incidence of cervical, vulvar and vaginal diseases associated with HPV 31, 33, 45, 52 or 58 decreased significantly [95%Cl (0.01, 0.07), OR = 0.03, P < 0.00001], with significant differences and statistical significance. Conclusion: HPV vaccination has stronger immunity than non-vaccinated people, and the number of patients is reduced by 90%; The incidence of CIN+ after vaccination with tetravalent vaccine was significantly lower than that without vaccination. The number of CIN+ was only 8% of that without vaccination with tetravalent vaccine, which had an obvious protective effect on the prevention of CIN+; The number of HPV 31, 33, 45, 52 and 58 related cervical, vulvar and vaginal diseases after vaccination with nine-valent HPV vaccine decreased by 97% compared with the tetravalent vaccine, indicating that the nine valent vaccine prevented more types of HPV virus than the tetravalent vaccine.