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(PAX1m/JAM3m)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x2检验比较两种采样方法PAX1m/JAM3m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％)、CIN2 43例(15.8％)、CIN3 29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PAX1m/JAM3m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％),PAX1m/JAM3m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％CI62.9％～93.0％)及 sPAX1m/JAM3m联合细胞学检测低度及以上鳞状上皮内病变(LBCLSIL+)[87.0％(95％CI67.9％～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.
Abstract
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(PAX1m/JAM3m)testing.The consistency between self-collected and physician-collected specimens for PAX1m/JAM3m 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 PAX1m/JAM3m.Results from spearman correlation analysis showed a positive correlation between the self-collected and physician-collected results of PAX1m/JAM3m detection,and the correlation coefficient R values are 0.858(P＜0.001)and 0.828(P＜0.001).The sensitivity and specificity of PAX1m/JAM3m 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 PAX1m/JAM3m combined with HPV16/18 detection,89.7％(95％CI 79.2％-95.2％),was the same as that of hrHPV detection in CIN2+and 96.0％(95％CI 80.4％-99.3％)in CIN3+,which is higher than 92.0％(95％CI 75.0％-97.8％)of hrHPV and 82.6％(95％CI 62.9％-93.0％)of LBC or the combination of sPAX1m/JAM3m and LBC low-grade and higher squamous intraepithelial lesion testing[87.0％(95％CI 67.9％-95.5％)].Conclusions Self-collected specimens by women for detection of PAX1 and JAM 3 methylation as a promising screening tool for cervical cancer has operational and clinical feasibility.The methylation test can optimize the current cervical cancer screening plan,reduce the number of referral women with false positive diagnosis to colposcopy,and is of great significance for reducing fertility protection and preventing missed diagnosis in women of childbearing age.
维普
万方数据