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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)\u2010based\u00a0histology image analyses could accelerate the discovery of better OC progression risk models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our CNN\u2010based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&amp;E slides. As a result, the OMRS model could\u00a0identify abnormal morphological features of the oral epithelium. By applying this model to OL slides, we hypothesized that the extent of OC\u2010like features identified in the OL epithelium would correlate with its progression risk. The OMRS model scored and categorized the OL cohort (<jats:italic>n<\/jats:italic>\u00a0=\u00a062) into high\u2010 and low\u2010risk groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OL patients classified as high\u2010risk (<jats:italic>n<\/jats:italic>\u00a0=\u00a031) were 3.98 (95% CI 1.36\u201311.7) times more likely to develop OC than low\u2010risk ones (<jats:italic>n<\/jats:italic>\u00a0=\u00a031). Time\u2010to\u2010progression significantly differed\u00a0between high\u2010 and low\u2010risk groups (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.003). The 5\u2010year OC development probability was 21.3% for low\u2010risk and 52.5% for high\u2010risk patients. The predictive\u00a0power of the OMRS model was sustained even after adjustment for age, OL site, and OL dysplasia grading (HR\u00a0=\u00a04.52, 1.5\u201313.7).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The ORMS model successfully identified OL patients with a high risk of OC development and can potentially benefit OC early diagnosis and prevention policies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5478","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T05:44:51Z","timestamp":1675230291000},"page":"7508-7518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Deep learning\u2010based pathology image analysis predicts cancer progression risk in patients with oral leukoplakia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7175-426X","authenticated-orcid":false,"given":"Xinyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Quantitative Biomedical Research Center, Department of Population and Data Sciences University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7847-9902","authenticated-orcid":false,"given":"Frederico O.","family":"Gleber\u2010Netto","sequence":"additional","affiliation":[{"name":"Department of Head &amp; Neck Surgery The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shidan","family":"Wang","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Department of Population and Data Sciences University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Rayra","family":"Martins\u2010Chaves","sequence":"additional","affiliation":[{"name":"Faculdade Ci\u00eancias M\u00e9dicas de Minas Gerais (FCM\u2010MG) Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Santiago","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery and Pathology, School of Dentistry Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadarajah","family":"Vigneswaran","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences The University of Texas Health Science Center at Houston School of Dentistry  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunangshu","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Head &amp; Neck Surgery The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"William N.","family":"William","sequence":"additional","affiliation":[{"name":"Department of Thoracic\u2010Head &amp; Neck Medical Oncology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Hospital BP A Benefic\u00eancia Portuguesa de S\u00e3o Paulo  Sao Paolo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Papadimitrakopoulou","sequence":"additional","affiliation":[{"name":"Department of Thoracic\u2010Head &amp; Neck Medical Oncology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Global Product Development Oncology, Pfizer, Inc.  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