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Improving patient selection and management in oral epithelial dysplasia
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Nankivell, Paul C. (2013) Improving patient selection and management in oral epithelial dysplasia. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b2722813~S1
Abstract
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
Item Type: | Thesis (PhD) | ||||
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Subjects: | R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine R Medicine > RC Internal medicine |
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Library of Congress Subject Headings (LCSH): | Dysplasia -- Treatment, Allocation of organs, tissues, etc., Epithelium -- Diseases -- Treatment, Mouth -- Diseases -- Treatment | ||||
Official Date: | August 2013 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Dunn, Janet; Mehanna, Hisham M. | ||||
Sponsors: | University Hospitals Coventry and Warwickshire NHS Trust; Royal College of Surgeons of England | ||||
Extent: | 313 leaves : illustrations, charts. | ||||
Language: | eng |
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