Hao Lin1, Tze-Chien Chen2, Ting-Chang Chang3, Ya-Min Cheng4, Chi-Hau Chen5, Tang-Yuan Chu6, Shih-Tien Hsu7, Cheng-Bin Liu8, Lian-Shung Yeh9, Kuo-Chang Wen10, Chia-Yen Huang11, Mu-Hsien Yu12. 1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 2. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taiwan. 3. Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, Taiwan. 4. Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Taiwan. 5. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taiwan. 6. Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Taiwan. 7. Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taiwan. 8. Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Taiwan. 9. Department of Obstetrics and Gynecology, China Medical University Hospital and College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan. 10. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan. 11. Department Obstetrics and Gynecology, Cathay General Hospital, Taiwan. 12. Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taiwan.
Abstract
OBJECTIVE: Our previous work revealed that host genes ZNF582, PTPRR, PAX1, and SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or worse (CIN3(+)). In this study, we used a standardized testing assay to evaluate the clinical efficacy of these biomarkers in the triage of cytological diagnoses of low-grade squamous intraepithelial lesions (LSILs), and compared the performance with human papillomavirus (HPV) testing. METHODS: This 2-year multicenter prospective study examined a population of 230 women from 12 medical centers who were diagnosed with LSILs on cervical cytology. Cervical scrapings were obtained prior to a colposcopy-directed biopsy for quantitative methylation analysis of ZNF582, PTPRR, PAX1, and SOX1, and HPV testing. Using logistic regression and receiver operating characteristic curve analyses, the abilities of methylated genes and HPV to predict CIN3(+) were assessed. RESULTS: Fifteen (6.5%) of the 230 women with a cytological diagnosis of LSIL were confirmed to have CIN3(+) after a colposcopy-directed biopsy. Among the 4 methylated genes, ZNF582 was found to be the best biomarker for detecting CIN3(+). The sensitivities for methylated ZNF582 and HPV testing were 73% and 80%, and the specificities were 71% and 28%, respectively. The odds ratio for predicting CIN3(+) using methylated ZNF582 was 6.8 (95% confidence interval (CI) 2.1-22.1), which was much better than HPV testing (OR=1.6, 95% CI 0.4-5.8). CONCLUSION: This is the first study to show that ZNF582 methylation analysis of cervical swabs may be a promising choice in the positive triage of cytological diagnoses of LSILs.
OBJECTIVE: Our previous work revealed that host genes ZNF582, PTPRR, PAX1, and SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or worse (CIN3(+)). In this study, we used a standardized testing assay to evaluate the clinical efficacy of these biomarkers in the triage of cytological diagnoses of low-grade squamous intraepithelial lesions (LSILs), and compared the performance with human papillomavirus (HPV) testing. METHODS: This 2-year multicenter prospective study examined a population of 230 women from 12 medical centers who were diagnosed with LSILs on cervical cytology. Cervical scrapings were obtained prior to a colposcopy-directed biopsy for quantitative methylation analysis of ZNF582, PTPRR, PAX1, and SOX1, and HPV testing. Using logistic regression and receiver operating characteristic curve analyses, the abilities of methylated genes and HPV to predict CIN3(+) were assessed. RESULTS: Fifteen (6.5%) of the 230 women with a cytological diagnosis of LSIL were confirmed to have CIN3(+) after a colposcopy-directed biopsy. Among the 4 methylated genes, ZNF582 was found to be the best biomarker for detecting CIN3(+). The sensitivities for methylated ZNF582 and HPV testing were 73% and 80%, and the specificities were 71% and 28%, respectively. The odds ratio for predicting CIN3(+) using methylated ZNF582 was 6.8 (95% confidence interval (CI) 2.1-22.1), which was much better than HPV testing (OR=1.6, 95% CI 0.4-5.8). CONCLUSION: This is the first study to show that ZNF582 methylation analysis of cervical swabs may be a promising choice in the positive triage of cytological diagnoses of LSILs.
Authors: Jin Huang; Guo Wang; Jie Tang; Wei Zhuang; Li-Ping Wang; Yu-Ligh Liou; Ying-Zi Liu; Hong-Hao Zhou; Yuan-Shan Zhu Journal: Int J Environ Res Public Health Date: 2017-02-22 Impact factor: 3.390
Authors: Abraham Pouliakis; Efrossyni Karakitsou; Charalampos Chrelias; Asimakis Pappas; Ioannis Panayiotides; George Valasoulis; Maria Kyrgiou; Evangelos Paraskevaidis; Petros Karakitsos Journal: Biomed Res Int Date: 2015-08-03 Impact factor: 3.411
Authors: Jane Shen-Gunther; Chiou-Miin Wang; Graham M Poage; Chun-Lin Lin; Luis Perez; Nancy A Banks; Tim Hui-Ming Huang Journal: Clin Epigenetics Date: 2016-09-13 Impact factor: 6.551