title: Factors predicting malignant transformation in oral potentially malignant disorders among patients accrued over a 10-year period in South East England.
abstract: OBJECTIVE
  The aims of the study were to determine how frequently oral potentially malignant disorders (OPMDs) transform to cancer and to identify clinical and histological factors determining the rates of transformation.
  
  
  METHODS
  The study included 1357 patients with biopsy-confirmed OPMDs seen at Guy's Hospital between 1990 and 1999 and followed up until 2005. The patients' details (name, date of birth, gender and any other relevant information) were matched to the Thames Cancer Registry (TCR) database and Office for National Statistics (ONS) to identify patients who subsequently developed oral cancer (ICD-10 C00-C06). From each patient's record, we identified their highest grade of dysplasia, graded as none, mild, moderate or severe. The outcome of principal interest was transformation to oral squamous cell carcinoma. To avoid co-existing malignancies, follow-up was started 6 months after the date of the index biopsy. Kaplan-Meier estimates and Cox proportional hazard analysis were undertaken to explore the factors associated with the time to transformation to oral cancer.
  
  
  RESULTS
  One thousand three hundred and fifty-seven patients were included in the study. The majority of patients were women (60.9%), and ∼30% were under 47 years of age. The most common OPMD was lichen planus/lichenoid reaction. Among all OPMDs, 204 (15.1%) had oral epithelial dysplasia (30 severe, 70 moderate and 104 mild). Thirty-five patients developed oral cancer over the follow-up period (2.6%). There was an association between dysplasia grade and time to transformation. Patients with severe dysplasia had a higher risk of transformation to oral cancer [HR 35.4 95% CI (14.2-88.3)] compared to those with no dysplasia. This association remained significant although attenuated [HR 21.6 95% CI (5.8-80.5)] following adjustment for sex, age, anatomical site of OPMD and diagnosis. A significant trend over dysplasia grades was evident (P < 0.0001). Transformation to oral cancer was also associated with increasing age (P = 0.0390).
  
  
  CONCLUSIONS
  In 2.6% of cases, OPMDs transformed to invasive cancer for a total person follow-up time of 12,273 years (mean 9.04 years). The severity of dysplasia is a significant predictor for malignant transformation.
authors.affiliation: Department of Clinical & Diagnostic Sciences, Oral Medicine, King's College London Dental Institute and the WHO Collaborating Centre for Oral Cancer and Precancer, London, UK. s.warne@kcl.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Warnakulasuriya
authors.forename: T
authors.initials: T
authors.lastname: Kovacevic
authors.forename: P
authors.initials: P
authors.lastname: Madden
authors.forename: V H
authors.initials: VH
authors.lastname: Coupland
authors.forename: M
authors.initials: M
authors.lastname: Sperandio
authors.forename: E
authors.initials: E
authors.lastname: Odell
authors.forename: H
authors.initials: H
authors.lastname: Møller
mesh_terms: D000367:Age Factors; D000368:Aged; D001706:Biopsy; D002180:Candidiasis, Oral / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D015331:Cohort Studies; D004848:Epithelium / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D006965:Hyperplasia; D007972:Leukoplakia, Oral / Q000473:pathology; D017676:Lichen Planus, Oral / Q000473:pathology; D017512:Lichenoid Eruptions / Q000473:pathology; D008131:London; D008179:Lupus Erythematosus, Discoid / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology*; D012042:Registries; D012189:Retrospective Studies; D012737:Sex Factors; D014062:Tongue Neoplasms / Q000473:pathology