子宫颈细胞学PAX1/JAM3双基因甲基化检测用于子宫颈癌筛查的多中心研究

A multicenter study on the accuracy of PAX1/JAM3 dual genes methylation testing for screening cervical cancer

目的探讨宫颈细胞学PAX1/JAM3双基因甲基化检测在子宫颈癌筛查中的应用价值。方法本研究为一项多中心前瞻性研究。2022年5至10月,在中国医学科学院北京协和医院、浙江大学医学院附属第二医院和浙江省人民医院妇科门诊行子宫颈癌机会性筛查的女性中,将接受液基薄层细胞学检测(TCT)、高危型人乳头瘤病毒(hrHPV)DNA检测与PAX1/JAM3双基因甲基化(PAX1 m/JAM3 m)检测者为研究对象,共1184例。基于hrHPV和细胞学结果,根据现行指南对于需要转诊阴道镜的女性提供相关检查和活检。根据组织病理学结果,研究比较各项检测方法及其组合用于子宫颈癌筛查的准确性。结果1184例研究对象的年龄[M(Q_(1),Q_(3))]为39(32,51)岁,其中子宫颈良性或慢性子宫颈炎(正常)、子宫颈上皮内瘤变(CIN)1、CIN2、CIN3和子宫颈癌分别为541例(45.7%)、273例(23.1%)、168例(14.2%)、140例(11.8%)和62例(5.2%)。根据病理学结果,PAX1 m/JAM3 m检测诊断CIN2或更严重病变(CIN2+)的灵敏度、特异度分别为74.1%和95.9%,诊断CIN3+的灵敏度、特异度分别为87.6%和86.8%。受试者工作特征曲线显示,对于诊断CIN3+,PAX1 m/JAM3 m优于TCT或hrHPV检测,曲线下面积(AUC)(95%CI)分别为0.872(0.847~0.897)、0.580(0.551~0.610)和0.503(0.479~0.515)(均P<0.05)。结论子宫颈脱落细胞中PAX1 m/JAM3 m检测对于诊断CIN2+和CIN3+均具有优异的准确性,优于传统的筛查方案和筛查策略。

Objective To explore the value of cervical cytologic DNA methylation for screening cervical cancer.Methods This study was a prospective multicenter study conducted from May to October 2022 in Peking Union Medical College Hospital,Zhejiang Provincial People′s Hospital,and the Second Affiliated Hospital of Zhejiang University School of Medicine.Women who accepted opportunistic cervical cancer screening in gynecological outpatient clinics were subjected to liquid-based thin-layer cytology testing(TCT),high-risk human papillomavirus(hrHPV)DNA testing and PAX1/JAM3 dual-genes methylation testing(PAX1 m/JAM3 m).Colposcopy evaluation and biopsy were offered to women according to current guidelines.The accuracies of various testing methods and their combinations were compared based on histological diagnosis.Results A total of 1184 samples diagnosed by histopathology were included in this study,consisting of 541 cases(45.7%)of benign cervical tissue or chronic cervicitis,273(23.1%)of cervical intraepithelial neoplasia(CIN)1,168(14.2%)of CIN2,140(11.8%)of CIN3,and 62(5.2%)of cervical cancer.The sensitivity and specificity of PAX1 m/JAM3 m testing for detecting CIN2 or more severe lesions(CIN2+)were 74.1%and 95.9%,respectively.The sensitivity and specificity of PAX1 m/JAM3 m testing for detecting CIN3+were 87.6%and 86.8%,respectively.Receiver operating characteristic curve analysis showed that,for detecting CIN3+,the area under curve of PAX1 m/JAM3 m testing(0.872,95%CI:0.847-0.897)was significantly superior to TCT testing(0.580,95%CI:0.551-0.610)or hrHPV testing(0.503,95%CI:0.479-0.515)(all P values<0.05).Conclusions The PAX1 m/JAM3 m test in cervical exfoliated cells has excellent accuracy for the diagnosis of both CIN2+and CIN3+,which is superior to traditional screening protocols and screening strategies.