h英国伦敦帝国理工学院Maria Kyrgiou团队研究了人乳头瘤病毒（HPV）疫苗接种对局部手术治疗后HPV感染和HPV相关疾病复发的影响。该研究于2022年8月3日发表在《英国医学杂志》上。

为了探讨在接受局部手术治疗的个体中，接种人乳头瘤病毒（HPV）疫苗对HPV感染风险和与HPV感染相关的复发性疾病的影响，研究组在PubMed（Medline）、Scopus、Cochrane、科学引文索引和ClinicalTrials.gov等大型数据库中检索从建库到2021年3月31日的相关文献，并进行系统回顾和荟萃分析。

筛选出报告接种疫苗的个体侵袭前生殖器疾病局部手术治疗后HPV感染的风险和与HPV感染相关的疾病复发的研究。主要终点指标是局部手术治疗后宫颈上皮内瘤变2级及以上（CIN2+）复发的风险，并根据个别研究报告进行随访。次要观察指标是HPV感染或与HPV感染相关的其他病变风险。

研究组分别使用ROBINS-I和RoB-2工具进行独立和重复数据提取和质量评估，用于观察研究和随机对照试验。对主要结局进行推荐分级的评估、制订与评价（GRADE）。观察研究和随机对照试验与随机对照试验的事后分析分别进行分析。使用随机效应荟萃分析模型计算合并风险比和95%置信区间。使用限制最大似然法作为异质性的估计量，并使用Hartung-Knapp-Sidik-Jonkman方法推导置信区间。

共有22篇文章符合审查的纳入标准；其中18项研究还报告了来自未接种疫苗组的数据，并纳入荟萃分析（12项观察研究、2项随机对照试验和4项随机对照实验的事后分析）。与未接种的参与者相比，接种疫苗的参与者CIN2+复发风险降低（11项研究，19909名参与者；风险比为0.43；I²=58%，τ²=0.14，中位随访36个月）。

当评估与HPV亚型HPV16或HPV18相关疾病的CIN2+复发风险时，疗效评估更加有力（6项研究，1879名参与者；风险比为0.26；I²=0%，τ²=0）。按GRADE评估的总体CIN2+和与HPV16或HPV18相关的CIN2+荟萃分析的置信度从非常低到中等，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性。

在接种疫苗的患者中，CIN3复发的风险也降低了，但不确定性很大（3项研究，17757名参与者；风险比为0.28；I²=71%，τ²=1.23）。外阴、阴道和肛门上皮内瘤变复发、生殖器疣、持续性和偶发性HPV感染缺乏获益证据，尽管每种结果的研究和参与者数量较少。

研究结果表明，HPV疫苗接种可能降低CIN复发的风险，特别是当与HPV16或HPV18相关时，局部手术治疗的女性。证据质量GRADE评估表明，这些数据是不确定的。需要进行大规模、高质量的随机对照试验，以确定接受HPV感染相关疾病治疗的女性接种HPV疫苗的有效性和成本水平。

附：英文原文

Title: Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis

Author: Konstantinos S Kechagias, Ilkka Kalliala, Sarah J Bowden, Antonios Athanasiou, Maria Paraskevaidi, Evangelos Paraskevaidis, Joakim Dillner, Pekka Nieminen, Bjorn Strander, Peter Sasieni, Areti Angeliki Veroniki, Maria Kyrgiou

Issue&Volume: 2022/08/03

Abstract:

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, 19909 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, 17757 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.

DOI: 10.1136/bmj-2022-070135

Source: https://www.bmj.com/content/378/bmj-2022-070135