In 2022, the World Health Organization (WHO) proposed new criteria for the diagnosis of oral epithelial dysplasia (OED), however their association with patient's outcome is still unknown. This study compared the different classification systems of OED and evaluate their efficacy in predicting malignant transformation. A total of 195 slides of leukoplakia and erythroplakia were graded according to the WHO 2017, 2022, and the Binary System classification, and were correlated with the lesion's evolution. A progressive increase in malignant transformation according to the severity of OED, with both the WHO and the Binary classification systems was detected. Among individual criteria, changes in cell morphology were independently associated with an increased risk of malignant transformation (HR = 2.8, 95%CI 1.1-7.5, p = 0.032). Considering the new set of OED criteria published in 2022, it was detected that a new cutoff of 4 architectural alterations and 6 cytological alterations predicts better malignant transformation. Malignant transformation was equally predicted by the OED classification systems. Due to the increased number of architectural and cytological features in WHO 2022, a new cutoff for classifying OED from low to high-grade considering 4 architectural and 6 cytological alterations is proposed. The findings allow a more accurate assessment of malignant transformation risk in OED.
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