Lai Hung-Cheng, Ou Yu-Che, Chen Tze-Chien, Huang Huei-Jean, Cheng Ya-Min, Chen Chi-Hau, Chu Tang-Yuan, Hsu Shih-Tien, Liu Cheng-Bin, Hung Yao-Ching, Wen Kuo-Chang, Yu Mu-Hsien, Wang Kung-Liahng
Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Medical University, Taipei, Taiwan.
Cancer Med. 2014 Aug;3(4):1062-74. doi: 10.1002/cam4.253. Epub 2014 May 3.
We aimed to determine whether PAX1/SOX1 methylation could be translated to clinical practice for cervical neoplasia detection when used alone and in combination with current cytology-based Pap screening. We conducted a multicenter case-control study in 11 medical centers in Taiwan from December 2009 to November 2010. Six hundred seventy-six patients were included in the analysis, including 330 in the training set and 346 in the testing set. Multiplex quantitative methylation-specific polymerase chain reaction (PCR) was performed with a TaqMan probe system using a LightCycler 480 Real-Time PCR System (Roche). The level of human papilloma virus (HPV) was analyzed using a Hybrid Capture 2 system (Digene). Receiver operating characteristic curves were generated to obtain the best cutoff values from the training data set. The sensitivities, specificities, and accuracies were validated in the testing set. The sensitivities for methylated ((m)) PAX1(m) and SOX1(m) and HPV testing for detecting CIN3(+) lesions were 0.64, 0.71, and 0.89, and the specificities were 0.91, 0.77, and 0.68, respectively. Combined parallel testing of PAX1(m)/SOX1(m) tests with Pap smearing showed superior specificity (0.84/0.71 vs. 0.66, respectively) and similar sensitivity (0.93/0.96 vs. 0.97) to the combination of Pap smear results and HPV testing. Thus, combined parallel testing using Pap smears and PAX1 or SOX1 methylation tests may provide better performance than a combination of Pap smears with HPV testing in detection for cervical neoplasia.
我们旨在确定单独使用以及与当前基于细胞学的巴氏筛查联合使用时，PAX1/SOX1甲基化是否可转化应用于子宫颈肿瘤检测的临床实践。2009年12月至2010年11月，我们在台湾的11个医疗中心开展了一项多中心病例对照研究。676例患者纳入分析，其中330例在训练集，346例在测试集。使用罗氏LightCycler 480实时荧光定量PCR系统，通过TaqMan探针系统进行多重定量甲基化特异性聚合酶链反应（PCR）。使用杂交捕获2系统（Digene）分析人乳头瘤病毒（HPV）水平。通过训练数据集生成受试者工作特征曲线以获得最佳临界值。在测试集中验证敏感性、特异性和准确性。甲基化（（m））PAX1（m）和SOX1（m）以及HPV检测用于检测CIN3（+）病变的敏感性分别为0.64、0.71和0.89，特异性分别为0.91、0.77和0.68。PAX1（m）/SOX1（m）检测与巴氏涂片联合平行检测显示，与巴氏涂片结果和HPV检测联合相比，特异性更高（分别为0.84/0.71对0.66），敏感性相似（分别为（0.93/0.96对0.97）。因此，在子宫颈肿瘤检测中，巴氏涂片与PAX1或SOX1甲基化检测联合平行检测可能比巴氏涂片与HPV检测联合具有更好的性能。
