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Four oral squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">OSCC<\/jats:styled-content>), 15 oral epithelial dysplasia (<jats:styled-content style=\"fixed-case\">OED<\/jats:styled-content>), nine oral lichen planus (<jats:styled-content style=\"fixed-case\">OLP<\/jats:styled-content>) and 14 oral epithelial hyperplasia (<jats:styled-content style=\"fixed-case\">OEH<\/jats:styled-content>) presenting with three fluorescence patterns including retained fluorescence (<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>), loss of fluorescence (<jats:styled-content style=\"fixed-case\">LAF<\/jats:styled-content>) with blanching (<jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">LAF<\/jats:styled-content> with no blanching (<jats:styled-content style=\"fixed-case\">LNB<\/jats:styled-content>) were assessed. Relative gene expression was measured through <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although each lesion type had a specific set of histology\u2010related differentially expressed genes (<jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s), all tested samples shared a number of <jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s, and we could not identify a discriminatory component between histological groups. Gene ontology enrichment revealed <jats:styled-content style=\"fixed-case\">LAF<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">OEH<\/jats:styled-content> was mostly due to changes in inflammation, cell cycle regulation and apoptosis, while in <jats:styled-content style=\"fixed-case\">OED<\/jats:styled-content> was due to inflammation, angiogenesis and extracellular matrix remodelling. Inflammatory reactions were associated with diascopic fluorescence (<jats:styled-content style=\"fixed-case\">DF<\/jats:styled-content>) for both <jats:styled-content style=\"fixed-case\">OEH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">OED<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Uncovering the molecular mechanisms underlying <jats:styled-content style=\"fixed-case\">LAF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DF<\/jats:styled-content> may lead to reduction in the number of false\u2010positive and false\u2010negative findings and improve the efficacy and utility of <jats:styled-content 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