女性阴道自采样本检测PAX1/JAM3双基因甲基化标志物作为子宫颈癌筛查的可行性评估  

Feasibility Evaluation of using PAX1/JAM3 methylation markers as cervical cancer screening for female self-collected samples

作　　者：余芙蓉[1] 马洁稚[2] 周希 李根林 彭嘉琪 李萍[4] 曾飞[2] 谢小兵[4] 董巍檑[1] Yu Furong;Ma Jiezhi;Zhou Xi;Li Genlin;Peng Jiaqi;Li Ping;Zeng Fei;Xie Xiaobing;Dong Weilei(Department of Gynecology and Obstetrics,the First Affiliated Hospital,University of South China,Hengyang 421001,China;Department of Obstetrics and Gynecology,Xiangya Third Hospital,Central South University,Changsha 410013,China;Hepatobiliary and Pancreatic Surgery,the First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Medical Laboratory and Pathology Center,the First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China)

机构地区：[1]南华大学附属第一医院妇科,衡阳421001 [2]中南大学湘雅三医院妇科,长沙410013 [3]湖南中医药大学第一附属医院肝胆胰、疝外科,长沙410007 [4]湖南中医药大学第一附属医院医学检验与病理中心,长沙410007

出　　处：《中华检验医学杂志》2024年第4期419-427,共9页Chinese Journal of Laboratory Medicine

基　　金：湖南省自然科学基金(2020JJ4859)。

摘　　要：目的探讨女性自采样本进行配对盒基因1(PAX1)/结合连接黏附分子3(JAM3)双基因甲基化检测在子宫颈癌筛查与绝经前后女性分层管理的应用价值。方法单中心横断面研究。2023年1—11月在阴道镜门诊同时收集女性自采样本及医生采样样本,分别进行PAX1/JAM3双基因甲基化(PAX1^(m)/JAM3^(m))检测,以组织病理学为标准。总计招募301例接受阴道镜检查女性,并对272例有组织病理与检测信息的女性进行统计分析。通过Spearman相关性分析和χ^(2)检验比较两种采样方法PAX1^(m)/JAM3^(m)检测结果的一致性。通过计算受试者操作特征曲线(ROC)和曲线下面积(AUC)比较女性自采样本甲基化检测与现行临床检测及其组合方法在临床研究中用于子宫颈癌筛查的效益。结果在所有招募的受试者中,正常子宫颈组织或慢性子宫颈炎102例(37.5%)、子宫颈上皮内瘤变1级(CIN1)72例(26.4%)、CIN243例(15.8%)、CIN329例(10.7%)、子宫颈癌26例(9.6%)。按最低检出量公式计算区分成为81例一致性研究组和191例临床研究组。Spearman相关性分析表明,自采样本和医生采样样本进行PAX1和JAM3双基因甲基化检测结果的卡氏评分呈正相关(r=0.858、0.828,P均<0.001);自采样本在临床研究中结果显示PAX1^(m)/JAM3^(m)检测诊断CIN2或更严重病变(CIN2+)的敏感度和特异度分别为77.6%(95%CI 65.3%~86.4%)和87.2%(95%CI 80.5%~91.9%),PAX1^(m)/JAM3^(m)联合人乳头瘤病毒16/18型(HPV16/18)检测的敏感度与高危人乳头瘤病毒(hrHPV)检测相同为89.7%(95%CI 79.2%~95.2%);在CIN3+时为96.0%(95%CI 80.4%~99.3%),优于hrHPV的92.0%(95%CI 75.0%~97.8%)、细胞学的82.6%(95%CI 62.9%~93.0%)及sPAX1^(m)/JAM3^(m)联合细胞学检测低度及以上鳞状上皮内病变(LBCLSIL+)[87.0%(95%CI 67.9%~95.5%)]。结论女性自采样本进行PAX1与JAM3双基因甲基化检测作为子宫颈癌筛查具有操作与临床可行性。Objective To explore the application value of PAX1/JAM3 methylation detection by cervical self-collected specimen in cervical cancer screening and the management of premenopausal and postmenopausal women.Method This study is a single center cross-sectional study.From January 2023 to November 2023,cervical self-collected and physician-collected specimens at the colposcopy clinic were detected the PAX1/JAM3 methylation(PAX1^(m)/JAM3^(m))testing.The consistency between self-collected and physician-collected specimens for PAX1^(m)/JAM3^(m) detection were compared based on histopathology.In addition,the clinical efficacy of methylation detection with high-risk human papillomavirus(hrHPV),liquid-based cytology(LBC),and their combination for cervical cancer screening were compared in the study.Results A total of 301 women were recruited to undergo referral colposcopy examination,and statistical analysis was conducted on 272 women with pathological and diagnostic information.Among them,102 cases(37.5%)were diagnosed as normal cervical tissue or chronic cervicitis,72 cases(26.4%)were cervical intraepithelial neoplasia grade 1(CIN1),43 cases(15.8%)were CIN2,29 cases(10.7%)were CIN3,and 26 cases(9.6%)were cervical cancer.According to the minimum quantity formula,they were divided into a consistency cohort of 81 participants and a validation cohort of 191 participants.The consistency between cervical self-collected and physician-collected specimens for detecting PAX1^(m)/JAM3^(m).Results from spearman correlation analysis showed a positive correlation between the self-collected and physician-collected results of PAX1^(m)/JAM3^(m) detection,and the correlation coefficient R values are 0.858(P<0.001)and 0.828(P<0.001).The sensitivity and specificity of PAX1^(m)/JAM3^(m) detection for diagnosing CIN2 or more severe lesions(CIN2+)were 77.6%[95%confidence interval(CI)65.3%-86.4%]and 87.2%(95%CI 80.5%-91.9%),respectively.In clinical performance comparison,the sensitivity of PAX1^(m)/JAM3^(m) combined with HPV16/18 detection,89.7%(

关 键 词：宫颈肿瘤 宫颈上皮内瘤样病变 DNA甲基化 自采样 

分 类 号：R737.33[医药卫生—肿瘤]