Objective To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment. Design Systematic review and meta-analysis Data sources PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021. Review methods Studies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was implemented for the primary outcome. Observational studies and randomised controlled trials were analysed separately from post hoc analyses of randomised controlled trials. Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals. Results 22 articles met the inclusion criteria of the review; 18 of these studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational studies, two randomised controlled trials, and four post hoc analyses of randomised controlled trials). The risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated (11 studies, 19 909 participants; risk ratio 0.43, 95% confidence interval 0.30 to 0.60; I2=58%, τ2=0.14, median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18 (six studies, 1879 participants; risk ratio 0.26, 95% confidence interval 0.16 to 0.43; I2=0%, τ2=0). Confidence in the meta-analysis for CIN2+ overall and CIN2+ related to HPV16 or HPV18, assessed by GRADE, ranged from very low to moderate, probably because of publication bias and inconsistency in the studies included in the meta-analysis. The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large (three studies, 17 757 participants; 0.28, 0.01 to 6.37; I2=71%, τ2=1.23). Evidence of benefit was lacking for recurrence of vulvar, vaginal, and anal intraepithelial neoplasia, genital warts, and persistent and incident HPV infections, although the number of studies and participants in each outcome was low. Conclusion HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision. GRADE assessment for the quality of evidence indicated that the data were inconclusive. Large scale, high quality randomised controlled trials are required to establish the level of effectiveness and cost of HPV vaccination in women undergoing treatment for diseases related to HPV infection. Systematic review registration PROSPERO CRD42021237350. All data relevant to the study are included in the article or uploaded as supplementary information.

中文翻译：

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人乳头瘤病毒（HPV）疫苗接种对 HPV 感染和局部手术治疗后 HPV 相关疾病复发的作用：系统评价和荟萃分析


目的探讨人乳头瘤病毒（HPV）疫苗接种对局部手术治疗个体HPV感染风险及HPV感染相关疾病复发的影响。设计 系统评价和荟萃分析 数据来源 PubMed (Medline)、Scopus、Cochrane、Web of Science 和 ClinicalTrials.gov 均从开始至 2021 年 3 月 31 日进行筛选。 评价方法 报告 HPV 感染风险和相关疾病复发的研究包括接种疫苗的个体在局部手术治疗浸润前生殖器疾病后 HPV 感染的情况。主要结局指标是局部手术治疗后宫颈上皮内瘤变 2 级或以上 (CIN2+) 复发的风险，并根据个别研究报告进行随访。次要结果指标是 HPV 感染或与 HPV 感染相关的其他病变的风险。使用 ROBINS-I 和 RoB-2 工具分别进行独立和重复的数据提取和质量评估，用于观察性研究和随机对照试验。对主要结果实施了建议评估、制定和评估分级 (GRADE)。观察性研究和随机对照试验与随机对照试验的事后分析分开进行分析。使用随机效应荟萃分析模型计算汇总风险比和 95% 置信区间。使用限制最大似然作为异质性的估计量，并使用 Hartung-Knapp-Sidik-Jonkman 方法导出置信区间。 结果 22篇文章符合综述纳入标准；其中 18 项研究还报告了未接种疫苗组的数据，并纳入荟萃分析（12 项观察性研究、两项随机对照试验和四项随机对照试验事后分析）。与未接种疫苗的个体相比，接种疫苗的个体 CIN2+ 复发风险降低（11 项研究，19 909 名受试者；风险比 0.43，95% 置信区间 0.30 至 0.60；I2=58%，τ2=0.14，中位数随访 36 个月，四分位距 24-43.5）。当评估与 HPV 亚型 HPV16 或 HPV18 相关的疾病的 CIN2+ 复发风险时，效果估计甚至更强（六项研究，1879 名受试者；风险比 0.26，95% 置信区间 0.16 至 0.43；I2=0%，τ2= 0）。通过 GRADE 评估，总体 CIN2+ 以及与 HPV16 或 HPV18 相关的 CIN2+ 荟萃分析的置信度从非常低到中等不等，可能是因为荟萃分析中包含的研究存在发表偏倚和不一致。接种疫苗的患者 CIN3 复发风险也降低，但不确定性很大（三项研究，17 757 名受试者；0.28、0.01 至 6.37；I2=71%，τ2=1.23）。尽管每种结果的研究和参与者数量都很低，但缺乏外阴、阴道和肛门上皮内瘤变、生殖器疣以及持续性和偶发性 HPV 感染复发的益处证据。结论 HPV 疫苗接种可能会降低接受局部切除治疗的女性 CIN 复发的风险，特别是与 HPV16 或 HPV18 相关的风险。证据质量的 GRADE 评估表明数据尚无结论。 需要大规模、高质量的随机对照试验来确定接受 HPV 感染相关疾病治疗的女性中 HPV 疫苗接种的有效性和成本水平。系统审评注册PROSPERO CRD42021237350。与研究相关的所有数据都包含在文章中或作为补充信息上传。