Abstract

Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)-basedhistology image analyses could accelerate the discovery of better OC progression risk models. Our CNN-based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model couldidentify abnormal morphological features of the oral epithelium. By applying this model to OL slides, we hypothesized that the extent of OC-like features identified in the OL epithelium would correlate with its progression risk. The OMRS model scored and categorized the OL cohort (n=62) into high- and low-risk groups. OL patients classified as high-risk (n=31) were 3.98 (95% CI 1.36-11.7) times more likely to develop OC than low-risk ones (n=31). Time-to-progression significantly differedbetween high- and low-risk groups (p=0.003). The 5-year OC development probability was 21.3% for low-risk and 52.5% for high-risk patients. The predictivepower of the OMRS model was sustained even after adjustment for age, OL site, and OL dysplasia grading (HR=4.52, 1.5-13.7). The ORMS model successfully identified OL patients with a high risk of OC development and can potentially benefit OC early diagnosis and prevention policies.

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