title: PAX1/SOX1 DNA methylation and cervical neoplasia detection: a Taiwanese Gynecologic Oncology Group (TGOG) study.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Lai
authors.forename: Yu-Che
authors.initials: YC
authors.lastname: Ou
authors.forename: Tze-Chien
authors.initials: TC
authors.lastname: Chen
authors.forename: Huei-Jean
authors.initials: HJ
authors.lastname: Huang
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Cheng
authors.forename: Chi-Hau
authors.initials: CH
authors.lastname: Chen
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
authors.forename: Shih-Tien
authors.initials: ST
authors.lastname: Hsu
authors.forename: Cheng-Bin
authors.initials: CB
authors.lastname: Liu
authors.forename: Yao-Ching
authors.initials: YC
authors.lastname: Hung
authors.forename: Kuo-Chang
authors.initials: KC
authors.lastname: Wen
authors.forename: Mu-Hsien
authors.initials: MH
authors.lastname: Yu
authors.forename: Kung-Liahng
authors.initials: KL
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008875:Middle Aged; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012372:ROC Curve; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D013624:Taiwan; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D051761:Paired Box Transcription Factors; C490906:SOX1 protein, human; D055748:SOXB1 Transcription Factors; C070835:PAX1 transcription factor
keywords: Cervical cancer screening; DNA methylation; PAX1; SOX1