title: Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting low-grade squamous intraepithelial lesions - a Taiwanese Gynecologic Oncology Group (TGOG) study.
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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taiwan.
authors.forename: Tze-Chien
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, Taiwan.
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Taiwan.
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taiwan.
authors.forename: Chi-Hau
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Taiwan.
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
authors.affiliation: Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taiwan.
authors.forename: Shih-Tien
authors.initials: ST
authors.lastname: Hsu
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Taiwan.
authors.forename: Cheng-Bin
authors.initials: CB
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, China Medical University Hospital and College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Lian-Shung
authors.initials: LS
authors.lastname: Yeh
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan.
authors.forename: Kuo-Chang
authors.initials: KC
authors.lastname: Wen
authors.affiliation: Department Obstetrics and Gynecology, Cathay General Hospital, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taiwan.
authors.forename: Mu-Hsien
authors.initials: MH
authors.lastname: Yu
mesh_terms: D000328:Adult; D019175:DNA Methylation; D005260:Female; D005819:Genetic Markers; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000302:isolation & purification; D011446:Prospective Studies; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology* / Q000821:virology
chemical_list: D005819:Genetic Markers; D051741:Kruppel-Like Transcription Factors; C577358:ZNF582 protein, human
keywords: DNA methylation; HPV testing; Low-grade squamous intraepithelial lesion