Diagnostic and prognostic biomarkers in oral leukoplakia and oral squamous cell carcinoma: a narrative review

Abstract Oral squamous cell carcinoma (OSCC) is the most frequently encountered form of oral cancer, and in 29 % of cases, it arises from preexisting lesions called Oral Potentially Malignant Disorders. Oral leukoplakia (OLK) is the most researched OPMD in the scientific literature. This review article was compiled by synthesizing evidence from studies published between 2020 and 2025 on biomarkers in OSCC and OLK to identify diagnostic and prognostic biomarkers for the development and progression of OSCC and for the risk of malignant transformation (MT) in OLK. Lactate dehydrogenase, chemerin, matrix metalloproteinase-9, and phytosphingosine have the highest sensitivity as biomarkers for the diagnosis and prognosis of OSCC. Compared with healthy controls, oral cancer patients had higher salivary levels of IL-8, IL-6, TNF-α, IL-1β, and IL-10. TNF-α exhibited the highest diagnostic accuracy for oral cancer. For OLK, podoplanin and loss of heterozygosity are the most promising, although p53 and PDPN are the most frequently reported proteins. DNA ploidy can also be a potential indicator of MT risk, either alone or in combination with histopathological grading of oral epithelial dysplasia. Novel markers, such as cancer stem cell markers, DAPK-1, maspin, cytokeratins 13, 17, and 19, provide new insights into OLK progression to OSCC. While some biomarkers have demonstrated statistical significance across various studies and settings, there is still no consensus on the most specific biomarker or the most valuable panel for diagnostic and clinical purposes in OSCC and OLK.