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Title: Improving patient selection and management in oral epithelial dysplasia
Author: Nankivell, Paul C.
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2013
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BACKGROUND Oral epithelial dysplasia has a malignant potential. Three inter-related challenges currently exist for this condition. Prediction of which lesions will progress to cancer is not possible, requiring most patients to undergo unnecessary treatment. Attempts to identify prognostic biomarkers are hampered by limited tissue availability. Surgery remains the mainstay of treatment, with significant functional consequences and poor efficacy in preventing malignant transformation. All three are addressed here, through improved identification of dysplastic lesions likely to become cancerous, validating high-throughput laboratory techniques in oral dysplasia, and assessing the feasibility of a novel chemoprevention trial in the UK. IMPROVING PATIENT SELECTION Improvements to the current best predictive method of histological grading were explored. The performance of the binary grading system was validated before improvements in its predictive ability made by altering its diagnostic threshold. Current prognostic biomarkers were then identified by systematic literature review. The hypothesis generated was that the Epidermal Growth Factor Receptor and related pathway biomarkers are prognostically significant. By examining the largest published oral dysplasia cohort, it was demonstrated that EGFR, COX-2 and tetraspanins CD9 and 151 possess a significant prognostic ability in oral dysplasia. VALIDATION OF TISSUE MICROARRAYS IN ORAL DYSPLASIA Tissue microarrays can maximise the utilisation of finite pathological archives. Their use in dysplasia was validated for the first time through the development of a novel tissue-sparing virtual-array technique. ALTERNATIVES TO SURGICAL TREATMENT A feasibility chemoprevention trial was designed and initiated. The main finding was that national multicentre participation would be required for adequate recruitment. The significant resources required mean it is not currently feasible to execute such a trial in a population with a low incidence of oral dysplasia like the United Kingdom. DISCUSSION In summarising the current literature, this thesis highlights the key challenges in managing oral dysplasia. Improvements in identifying cases at highest risk of transformation have been made and will direct future work in a prospective cohort. Difficulties highlighted during the feasibility trial are already guiding the design of future trials.
Supervisor: Not available Sponsor: University Hospitals Coventry and Warwickshire NHS Trust ; Royal College of Surgeons of England
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RA0421 Public health. Hygiene. Preventive Medicine ; RC Internal medicine