Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
Department Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Acta Obstet Gynecol Scand. 2024 Jun;103(6):1028-1035. doi: 10.1111/aogs.14827. Epub 2024 Mar 13.
The role of multiple high-risk human papillomavirus (HR-HPV) infections on the occurrence of persistence/recurrence of high-grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated.
A systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022.
Out of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed-up and included in the meta-analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3-23.5) in multiple and 14.3 (95% CI: 10.1-19.2) in single HR-HPV infections detected shortly before or at surgery. The pooled rate of multiple HR-HPV infections was 25% (95% CI: 20.4-30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08-1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR-HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR-HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18-1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow-up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17-2.37, heterogeneity = 37%). Multiple HR-HPVs infection detected during follow-up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68-1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low-moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23-2 for low-moderate risk of bias and OR: 1.06, 95% CI: 0.65-1.75 for high risk of bias; p-value for subgroup differences = 0.17).
Multiple HR-HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow-up plan.
本研究评估了多重高危型人乳头瘤病毒（HR-HPV）感染在宫颈上皮内瘤变（CIN）锥切/手术后高级别鳞状上皮内病变（HSIL）持续/复发中的作用。
对 Pubmed/Medline、Scopus、Cochrane 数据库从成立到 2023 年 6 月 30 日进行了系统检索。三名评审员独立筛选了入选研究的摘要，并从全文文章中提取数据。随后对数据进行制表和比较，以确保一致性。根据 OSQE 方法评估每个纳入研究的偏倚。PROSPERO 注册号 CRD42023433022。
在筛选出的 1606 条记录中，有 22 篇全文文章符合纳入标准。共有 8321 名因 HSIL 接受（环电切除术、激光或手术）治疗的患者接受了随访，并纳入了荟萃分析。在多重 HR-HPV 感染中，总体持续存在和/或复发的合并患病率为 17.6%（95%CI：12.3-23.5），在单次 HR-HPV 感染中为 14.3%（95%CI：10.1-19.2）。多重 HR-HPV 感染的发生率为 25%（95%CI：20.4-30）。在统计学上，与单一 HR-HPV 感染相比，多重 HR-HPV 感染的 HSIL 持续存在和/或复发的组织学确认的比值比（OR）显著更高（OR：1.38，95%CI：1.08-1.75，p=0.01，异质性=39%）。在多重 HR-HPV 感染患病率≥25%（12 项研究，N=3476）（OR：1.47，95%CI：1.18-1.84，异质性=0%）和评估至少 6 个月阴性随访后真正的组织学证实复发的研究（9 项研究，N=5073）（OR：1.67，95%CI：1.17-2.37，异质性=37%）中，HSIL 持续/复发的风险更为显著。尽管纳入的研究数量较少（4 项研究，N=1248）（OR：0.98，95%CI：0.68-1.39，异质性=0%），但在随访期间检测到的多重 HR-HPV 感染对复发风险没有影响。在亚组分析中，纳入研究的偏倚风险（低/中度与高）对 HSIL 持续/复发的比值比（OR：1.57，95%CI：1.23-2 为低/中度偏倚风险，OR：1.06，95%CI：0.65-1.75 为高偏倚风险；p 值为亚组差异=0.17）有较小但无统计学意义的影响。
在标准治疗 HSIL 时，多重 HR-HPV 感染会导致 HSIL 持续/复发的风险略有增加，应在随访计划中考虑到这一点。
