Photodynamic therapy (PDT) is an alternative microinvasive approach with satisfying results in the treatment of oral leukoplakia (OL). PDT combined with laser irradiation shows promise, safety and efficacy in treating OL. The efficacy of waterlase (YSGG) combined with PDT was studied by brush and tissue biopsy. Seventy-one patients with histologically diagnosed OL were enrolled, including patients with mild to moderate dysplasia, severe dysplasia and various dysplastic tissues. Patients were evaluated at baseline (t0), the end of treatment (t1) and 1 year later (t2). At t1, PDT showed a significant therapeutic effect on OL with mild to moderate dysplasia. Clinical and histological examinations revealed 60 cases (84.51%) of complete remission and 11 cases (15.49%) of partial remission. On brush biopsy, all PDT-treated patients showed reduced aneuploidy and normal histological findings. Unfortunately, at t2, 9 patients relapsed with OL, which may be related to continued smoking and betel nut chewing. At t2, 5 patients developed new severe epithelial dysplasia and even carcinoma in situ in other areas, mostly the tongue. ALA-mediated PDT combined with YSGG is effective in treating OL, particularly that with mild to moderate dysplasia. However, severe dysplasia may present undesirable effects, and the mechanism remains to be further investigated. ALA-mediated PDT combined with YSGG provides a new method for OL treatment.

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