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UBC Theses and Dissertations

Oral second primary tumour risk predictors : clinical factors and loss of heterozygosity Prelec, Jelena


Oral squamous cell carcinoma (SCC) has a poor survival rate mainly due to late stage diagnosis and the high risk of developing second primary tumours (SPTs). Risk factors associated with progression of primary oral premalignant lesions (OPLs) to SCC have been validated; however, little research has been done on the risk predictors of SPTs. The objective of this thesis was to identify the demographic, clinicopathological and molecular risk factors associated with oral SPTs as well as those associated with second oral premalignant lesion (SOPL) progression to an oral SPT. From a cohort of the Oral Cancer Prediction Longitudinal study, data collected included: 1) demographic and habit information; 2) primary tumour information; 3) clinicopathological features during follow-up; and 4) toluidine blue (TB) and florescence visualization results. SOPL biopsy samples were analyzed for loss of heterozygosity (LOH) at regions previously identified as high risk for primary OPL progression. Of 296 patients who were followed-up subsequent to curative primary tumour treatment, 23 (8%) developed SPTs. Sixty-seven (23%) patients developed SOPLs, of which nine (14.5%) progressed to SPTs. Patients with primary tumours located on low-risk sites had an increased risk of SPTs (P=0.004) and SOPLs (P=0.009). Tobacco (P=0.046) and alcohol consumption (P=0.019) were each associated with the presence of SOPLs. The presence of an SOPL was associated with risk for SPT development, independent from histopathological diagnosis (P<0.001). TB was not only effective in identifying SPT development but was a valuable tool for predicting SOPL risk of progression to an SPT. Additionally, the majority of SOPLs had an LOH on at least one of the three chromosomal arms (9p, 3p and17p). The results suggest it is necessary to increase surveillance, to roughly six years following treatment in order to improve on the early detection of SOPLs and address the risk factors for SPTs. Data also supports the need to routinely biopsy SOPLs in order to provide a timely diagnosis and provide samples for the analysis of LOH. Ultimately translating this knowledge to the clinical management of patients has the potential to identify patients who are at high-risk for SPTs and improve long-term survival rates.

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