title: CpG island methylation profile in non-invasive oral rinse samples is predictive of oral and pharyngeal carcinoma.
abstract: BACKGROUND
  There are currently no screening tests in routine use for oral and pharyngeal cancer beyond visual inspection and palpation, which are provided on an opportunistic basis, indicating a need for development of novel methods for early detection, particularly in high-risk populations. We sought to address this need through comprehensive interrogation of CpG island methylation in oral rinse samples.
  
  
  METHODS
  We used the Infinium HumanMethylation450 BeadArray to interrogate DNA methylation in oral rinse samples collected from 154 patients with incident oral or pharyngeal carcinoma prior to treatment and 72 cancer-free control subjects. Subjects were randomly allocated to either a training or a testing set. For each subject, average methylation was calculated for each CpG island represented on the array. We applied a semi-supervised recursively partitioned mixture model to the CpG island methylation data to identify a classifier for prediction of case status in the training set. We then applied the resultant classifier to the testing set for validation and to assess the predictive accuracy.
  
  
  RESULTS
  We identified a methylation classifier comprised of 22 CpG islands, which predicted oral and pharyngeal carcinoma with a high degree of accuracy (AUC = 0.92, 95 % CI 0.86, 0.98).
  
  
  CONCLUSIONS
  This novel methylation panel is a strong predictor of oral and pharyngeal carcinoma case status in oral rinse samples and may have utility in early detection and post-treatment follow-up.
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, 160 Panzeca Way, ML0056, Cincinnati, OH 45267 USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Langevin
authors.affiliation: Department of Epidemiology, Brown University, Providence, RI USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Eliot
authors.affiliation: Department of Epidemiology, Brown University, Providence, RI USA.
authors.forename: Rondi A
authors.initials: RA
authors.lastname: Butler
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Cheong
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, 160 Panzeca Way, ML0056, Cincinnati, OH 45267 USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Environmental Health, Boston University School of Public Health, Boston, MA USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: McClean
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, Kansas City, KA USA.
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.affiliation: Department of Epidemiology, Brown University, Providence, RI USA ; Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Box G-E3, Providence, RI 02912 USA.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
keywords: Biomarkers; DNA methylation; Head and neck cancer; Infinium; Mouthwash