Implications of Podoplanin Overexpression in the Malignant Transformation of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis

Objective: To evaluate the degree of current evidence through a systematic review and meta-analysis on the association between podoplanin overexpression and the malignant transformation of oral potentially malignant disorders (OPMDs). Methods: A systematic search was performed in the MEDLINE (through PubMed), Embase, Scopus, and Web of Science databases for primary-level research published before December 2024, strictly designed as longitudinal cohorts with follow up data, and no restrictions by language or publication date. The Quality in Prognosis Studies QUIPS tool (developed by the Cochrane Prognosis Methods Group) was applied in order to assess the methodological quality and risk of bias. Meta-analyses, subgroup meta-analyses, sensitivity, and small-study effects analyses were performed. Results: Twelve primary-level studies met the eligibility criteria and were included, which followed up 857 OPMDs patients over time. Podoplanin overexpression was significantly associated with an increased risk of the malignant transformation of OPMDs (RR = 3.64, 95% CI = 2.18–6.10, p < 0.001). Podoplanin also proved to be a valuable biomarker in the malignant transformation of all investigated OPMDs (oral leukoplakia: p < 0.001; erythroplakia: p = 0.05; oral lichen planus: p = 0.02; discoid lupus erythematosus: p = 0.009). In addition, podoplanin overexpression was significantly associated with an increased risk of cancer development in several study subgroups with methodological implications (anti-podoplanin D2-40 antibody: p < 0.001; membrane and cytoplasm staining: p < 0.001; antibody dilution at 1:100: p < 0.001; overnight incubation: p < 0.001; 4 °C incubation: p < 0.001; cut-off point > 1%: p < 0.001; low risk of bias: p < 0.001). Conclusions: This systematic review and meta-analysis, on the basis of the evidence, indicates that podoplanin overexpression is a predictor of an increased risk of malignant transformation in OPMDs, singularly in oral leukoplakias. Its evaluation using immunohistochemical methods would be advisable in pathology laboratories.