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Use of autofluorescence in the detection of oral premalignant lesions in high-risk populations Ng, Samson Pak Yan

Abstract

Objectives: The current gold standard and more recent molecular markers in prediction of cancer risk for oral premalignant lesions (OPLs) rely upon biopsy samples of the OPLs. 'Clinicians' decision of when and where to biopsy would therefore heavily influence the results of histology and molecular markers. Unfortunately current clinical parameters used to make such decisions are far from adequate. The, objective of this thesis was to establish a multi-spectral fluorescent visualization (FV) technique and examine the potential role of FV as a visual aid to identify high-risk OPLs by examining the relationship between FV positivity and the conventional clinicopathological risk factors, including (1) cancer history, (2) clinical risk factors, (3) Toluidine blue (TB) staining, and (4) pathology. Materials and Method: 143 patients with a history of oral dysplasia (61) or oral cancer (82) were recruited from an ongoing prospective study (Oral Health Study) in the Oral Dysplasia Clinic at British Columbia Cancer Agency. Information collected included: FV results, demographics (age, gender, ethnicity), tobacco habit, history of oral cancer, TB staining, and clinicopathological findings. The FV examination was performed in a dark room. The oral mucosa was illuminated by an external light source with excitation wavelengths of 400 - 460 nm (violet/blue). The autofluorescence of oral tissue (normally pale green, defined as FV negative) was visualized by the examiner wearing glasses with longpass and notch filters that would only allow passage of green and red/orange fluorescence. Loss of the normal pale green colour or change of the colour to orange red are defined as FV +. Results: Of the 143 patients, 83 showed 1 or more FV positive oral sites and 60 showed no FV positive sites. There were no differences in the demographics and habits between FV positive and negative patients. A total of 319 oral sites from the 143 patients were examined with FV and 138 (43%) of these were FV positive. Cancer history of patients: There was no difference in either the % of patients with positive FV or the % of positive FV sites between patients with or without a history of oral cancer. Clinical risk factors (clinical diagnosis of OPLs): FV positive lesions showed a higher cancer risk as judged by clinical risk factors or diagnosis. Compared to FV negative lesions, FV positive lesions showed a significantly lower % of lesions diagnosed clinically as normal or equivocal (P < 0.0001), higher % of lesions diagnosed clinically as OPLs (P < 0.0001), were larger (P = 0.018) and more likely to be nonhomogeneous in appearance (P= 0.017). TB staining: FV positive lesions showed a higher cancer risk as judged by TB staining. A significantly higher % of FV positive lesions were TB positive compared to the FV negative lesions (P < 0.0001). Pathology: FV positive lesions showed a higher cancer risk as judged by pathology. A significantly higher % of FV positive lesions were dysplastic as compared to the FV negative lesions (P < 0.0001), and 91% of the 31 high-grade dysplasias were FV positive. Of 10 paired biopsies of oral lesions that were partly FV positive and negative (1 from FV + area, and another from FV - area but the same clinically similar-looking lesion), 6 pairs showed that the FV positive biopsy has the same histological diagnosis as the matching FV negative biopsy, and 4 showed that the FV positive biopsy with higher histological severity than the FV negative matching biopsies. Conclusion: This is the first study to investigate direct FV as a tool to identify high-risk OPLs in a large number of patients. As judged by clinical risk factors, TB staining and pathological findings, FV positivity seemed to identify high-risk OPLs. FV, a non-invasive procedure, could be a valuable visual aid to facilitate the decision of when and where to biopsy oral lesions.

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