Oral squamous cell carcinoma (SCC) is a lethal, deforming disease of global significance and rising incidence. In 2011, 6,767 new cases and 2,056 deaths occurred in the UK. Cancers are preceded by oral potentially malignant disorders (PMD), recognizable mucosal diseases harbouring significantly increased risk of carcinoma. These manifestations offer clinicians a ‘therapeutic window’ to intervene during carcinogenesis, although contemporary practice remains unable to predict individual lesion behaviour or quantify risk for malignant transformation. No clear management guidelines exist and available scientific literature is unable to answer the fundamental question whether intervention prevents cancer. This MD thesis includes 7 published papers on oral pre-cancer and 4 observational studies from a specialist PMD service coordinated by the author in Newcastle upon Tyne in Northern England. PMD management involves a complex interaction between patients, clinicians’ views on diagnosis and treatment and histopathological assessment of mucosal biopsy specimens. Uncertainty regarding the ‘potentially malignant state’ remains a pernicious influence throughout. Newcastle PMD patients were profiled as predominantly male, with a median age of 60yrs, and regular users of both tobacco and alcohol. Most presented with single-site disease, primarily leukoplakia on the floor of mouth and ventro-lateral tongue, with over 80% exhibiting epithelial dysplasia on histopathological examination. Approximately 70% underwent interventional therapy using CO2 laser surgery. 840 laser treatments were performed between 1996 and 2015 and the efficacy of laser intervention was examined by reviewing clinico-pathological details and clinical outcome for 590 PMD patients followed for a mean of 7.3yrs. Histopathology required ‘up-grading’ in 36% following definitive examination of laser excision specimens. 74.2% of patients were disease free, primarily younger patients with ‘low-grade’ dysplasia, 9% exhibited persistent disease and were older with gingival lesions often proliferative verrucous leukoplakia (PVL). In 12%, unexpected SCC was identified on excision, whilst 4.8% transformed to malignancy. Interventional laser surgery facilitates definitive diagnosis and efficacious treatment, allows early diagnosis and treatment of SCC, identifies patients at risk of progressive disease and defines clinical outcome categories. Evidence is lacking, however, that intervention halts the progress of carcinogenesis. Multi-centre, prospective, randomized, controlled trials are needed to confirm the efficacy of interventional surgery, to characterise PMD natural history and to disseminate research findings. It is hoped that the clinical work presented in this MD thesis will inform and encourage further research into PMD and lead to a reduction in the incidence of malignancy and improved morbidity and mortality.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:698958 |
| Date | January 2016 |
| Creators | Thomson, Peter |
| Contributors | Turner, James |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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