HPV16长控制区甲基化与宫颈上皮内瘤变2级及以上病变关系的Meta分析

郭翀宇; 王金桃; 冉朝霞; 巩璐; 朱京京; 李德铖; 丁玲

Abstract

郭翀宇,王金桃,冉朝霞,巩璐,朱京京,李德铖,丁玲.HPV16长控制区甲基化与宫颈上皮内瘤变2级及以上病变关系的Meta分析[J].Chinese journal of Epidemiology,2022,43(11):1821-1827

HPV16长控制区甲基化与宫颈上皮内瘤变2级及以上病变关系的Meta分析

The correlation between methylation in HPV16 long control region and cervical intraepithelial neoplasia grade 2 or more: a Meta-analysis

Received:March 07, 2022

DOI：10.3760/cma.j.cn112338-20220307-00172

KeyWord: 人乳头瘤病毒 DNA甲基化宫颈上皮内瘤变 Meta分析

English Key Word: Human papillomavirus DNA methylation Cervical intraepithelial neoplasia Meta-analysis

FundProject:国家自然科学基金（81703313，81872705）；山西省自然科学研究面上项目（202103021224354）

Author Name	Affiliation	E-mail
Guo Chongyu	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
Wang Jintao	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
Ran Zhaoxia	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
Gong Lu	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
Zhu Jingjing	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
Li Decheng	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
Ding Ling	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China	dingling79@163.com

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Abstract:

目的系统评价和分析人乳头瘤病毒16型（HPV16）长控制区（LCR）甲基化与宫颈上皮内瘤变2级及以上病变（CIN2+）之间的相关性。方法计算机系统检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普数据库等，检索国内外公开发表的中英文文献，按纳入排除标准筛选文献，检索年限为建库至2022年2月27日。采用RevMan 5.3和Stata 15.1软件进行统计学分析。结果最终纳入17篇文献，研究对象共1 421例。Meta分析结果显示，HPV16 LCR甲基化与CIN2+关系的合并效应OR值为1.56（95%CI：0.70~3.47）。亚组分析结果显示，5'端、增强子区和启动子区甲基化与CIN2+均未显示相关性；4个E2结合位点（E2BS）中，E2BS1、E2BS3和E2BS4甲基化增加CIN2+的发生风险，OR值分别为3.92（95%CI：1.92~7.99）、10.50（95%CI：3.67~30.04）和3.65（95%CI：1.58~8.41），由于文献篇数限制，未对E2BS2进行亚组分析；在不同地区人群来源中，中国人群CIN2+的发生风险与HPV16 LCR甲基化具有相关性，OR值为2.14（95%CI：1.31~3.50）；对HPV16 LCR进行焦磷酸测序的人群CIN2+的发生风险与HPV16 LCR甲基化具有相关性，OR值为1.75（95%CI：1.03~2.98）。结论 CIN2+的发生风险与HPV16 LCR E2BS的甲基化存在相关性。

English Abstract:

Objective To investigate the correlation between methylation in human papillomavirus 16 (HPV16) long control region (LCR) and cervical intraepithelial neoplasia grade ≥ 2 (CIN2+). Methods The literature retrieval was conducted by using the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang data and Weipu according to the inclusion and exclusion criteria, and the retrieval period was from the establishment of the databases to February 27^th, 2022. Software RevMan 5.3 and Stata 15.1 were used for Meta-analysis. Results A total of 17 literatures were included involving 1 421 subjects. Results of Meta-analysis showed that OR of the correlation between methylation of HPV16 LCR and CIN2+ was 1.56 (95%CI:0.70-3.47). Subgroup analysis showed that methylation of the 5' terminal, enhancer and promoter regions were not associated with CIN2+, while in four E2 binding sites (E2BS), the methylation of E2BS1, E2BS3 and E2BS4 increased the risk of CIN2+, with the ORs of 3.92 (95%CI:1.92-7.99), 10.50 (95%CI:3.67-30.04) and 3.65 (95%CI:1.58-8.41), respectively. However, subgroup analysis on E2BS2 was not performed due to the limitation of the number of literatures. According to the different sources of population, the risk of CIN2+ in Chinese population was associated with methylation of HPV16 LCR (OR=2.14, 95%CI:1.31-3.50). There was a correlation between the risk of CIN2+ and HPV16 LCR methylation in the population with pyrosequencing of HPV16 LCR, and OR was 1.75 (95%CI:1.03-2.98). Conclusion The risk of CIN2+ is correlated with the methylation of E2BS in HPV16 LCR, which can be used as potential biomarkers.

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