抑癌基因甲基化检测在宫颈病变筛查中的作用  

The role of tumor suppressor gene methylation detection in screening of cervical lesions

作　　者：马莉[1] 卞美璐[1] 于欢[1] 李茜[1] 张庆霞[1] 阳艳军[1] 贺桂芳[1] 陈庆云[1] 陈曦 邹志远 刘红刚[3] MA Li;BIAN Mei-lu;YU Huan(Department of Obstetrcis and Gynecology,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]中日友好医院妇产科,北京100029 [2]广东省HPV工程研究开发中心,广东惠州516000 [3]首都医科大学附属北京同仁医院病理科,北京100005

出　　处：《中日友好医院学报》2021年第2期73-76,80,共5页Journal of China-Japan Friendship Hospital

摘　　要：目的:探讨人乳头瘤病毒(HPV)感染及抑癌基因甲基化检测在宫颈病变筛查中的作用。方法:分析2019年10月~2020年1月在中日友好医院门诊因HPV感染或液基细胞学检查(LBC)异常而就诊的机会性筛查女性494例,采用聚合酶链反应法(PCR)+导流杂交法测定HPV分型,定量甲基化-特异性PCR测定抑癌基因PAX-1、SOX-1甲基化水平,以组织病理学诊断为金标准,评价其筛查宫颈病变的效果。结果:(1)HPV感染增加≥高级别鳞状上皮内病变(HSIL)病变的发生风险(OR=1.949,95%CI:1.321~2.875,P<0.01)。(2)HPV16型感染是甲基化阳性、HSIL和SCC的危险因素(均P<0.01)。(3)甲基化阳性的危险因素包括高危型HPV感染、HPV单一感染、HPV持续感染及具有HPV感染病史者(均P<0.01)。(4)联合HPV37分型和甲基化检测筛查≥HSIL病变的敏感性和阴性预测值分别为97.6%和96.3%。结论:抑癌基因甲基化与HPV感染密切相关,是≥HSIL病变的危险因素;甲基化检测作为HPV37分型检测的分流,可提高≥HSIL病变的筛查效果,有望成为宫颈癌筛查的潜在分子标志物。Objective:To evaluate the role of human papillomavirus(HPV)infection and methylation detection in screening for cervical lesions.Methods:From October 2019 to January 2020,494 cases of opportunistic screening females were analysised,they were from the Center of Cervical Lesion Diagnosis and Treatment of China-Japan Friendship Hospital,with HPV infection or abnormal liquid based cytology test results.We used polymerase chain reaction(PCR)and diversion hybrid to detect the classification of HPV 37 infection,and quantitative methylation specific PCR method to determine the methylation level of the PAX-1 and SOX-1 gene.Their roles in the screening of cervical lesions were evaluated with tissue pathology as the golden standard.Results:(1)HPV infection was a risk factor for≥high-grade squamous intraepithelial lesion(HSIL)(OR=1.949,95%CI:1.321~2.875,P<0.01).(2)HPV16 infection was the risk factor of methylation positivity,HSIL and SCC(all P<0.01).(3)Methylation positive risk factors were high-risk type of HPV infection,a single HPV infection,HPV persistent infection and a history of HPV infection(all P<0.01).(4)The sensitivity and negative predictive values of combined HPV37 typing and methylation tests for screening≥HSIL lesions were97.6%and 96.3%,respectively.Conclusion:Methylation was closely related to HPV infection,both of them were the risk factors for≥HSIL lesions.Methylation detection,as a shunt of HPV37 classification test,could improve the sensitivity and negative predictive value of≥HSIL lesions,and may be a potential molecular marker for cervical cancer screening.

关 键 词：人乳头瘤病毒 甲基化 PAX-1 SOX-1 宫颈上皮内病变 

分 类 号：R737.33[医药卫生—肿瘤]