title: P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study.
abstract: BACKGROUND
  Silencing of P16 through methylation and locus deletion is the most frequent early events in carcinogenesis. The aim of this study is to prospectively determine if early P16 methylation is a predictor for oral cancer development.
  
  
  METHODS
  Patients (n = 181) with mild or moderate oral epithelial dysplasia (OED) were recruited into the double blind multicentre cohort. P16 methylation was analyzed using the MethyLight assay. Progression of OEDs was monitored for a minimum 3 year follow-up period.
  
  
  RESULTS
  P16 methylation-informative cases (n = 152) were enrolled in the prospective multicenter cohorts with an ultimate compliance of 96.7%. OED-derived squamous cell carcinomas were observed in 21 patients (14.3%) during the follow-up (median, 41.0 months). The cancer progression rate from the P16 methylation-positive patients was significantly increased when compared to P16 methylation-negative patients [27.1% vs 8.1%; adjusted odds ratio = 4.6; P = 0.006]. When the P16 methylation-positive criteria were used as a biomarker for early prediction of cancer development from OEDs, sensitivity and specificity of 62% and 76% were obtained, respectively.
  
  
  CONCLUSIONS
  P16 methylation is unequivocally a marker for determining the malignant potential of OED and there is no need for further research regarding this aspect.
  
  
  BACKGROUND
  National Basic Research Programs of China (2011CB504201 and 2015CB553902), Beijing Science and Technology Commission (Z090507017709016), and Beijing Municipal Administration of Hospital (XM201303) to Dajun Deng. The funding agencies have no role in the actual experimental design, patient recruitment, data collection, analysis, interpretation, or writing of this manuscript.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Stomatology, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Capital Medical University School of Stomatology, China.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Liu
authors.affiliation: Fourth Military Medical University Hospital of Stomatology, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Dong
authors.affiliation: Beijing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Aetiology, Peking University Cancer Hospital and Institute, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Stomatology, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Stomatology, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Capital Medical University School of Stomatology, China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Aetiology, Peking University Cancer Hospital and Institute, China.
authors.forename: Liankun
authors.initials: L
authors.lastname: Gu
authors.affiliation: Capital Medical University School of Stomatology, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Aetiology, Peking University Cancer Hospital and Institute, China.
authors.forename: Dajun
authors.initials: D
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D018450:Disease Progression; D004311:Double-Blind Method; D055088:Early Detection of Cancer; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D015999:Multivariate Analysis; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Methylation; Oral dysplasia; P16; Prospective cohort; Transformation