Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Objective: To identify the performance of podoplanin expression in risk stratification of oral pre-malignant diseases (OMPDs) as high or low risk for malignant transformation.
Background: Podoplanin is a glycoprotein located in the transmembrane of various cell types such as lymphatic endothelial cells (LECs) and fibroblastic reticular cells (RCs). Podoplanin is a well-known marker for lymphatic vessels, and as a cancer-associated fibroblast (CAF) marker associated with poor prognosis in various cancers, such as lung and pancreatic adenocarcinoma. We investigated the significance of podoplanin as biomarker for malignancy potential of OPMD.
Data Sources: CINAHL Cochrane Library, PubMed, and Scopus.
Methods: A systematic search was done in accordance with PRISMA guidelines, for articles reporting podoplanin expression in pre-malignant oral disease. Specific diseases of interest were oral leukoplakia (OL), oral erythroplakia (OE), oral submucosal fibrosis (OSF), and oral squamous cell carcinoma (OSCC). Podoplanin expression was graded on a scale from 0-4 with a grade of 0-1 qualifying as negative podoplanin expression and a grade of 2-4 qualifying as positive podoplanin expression. A grade of zero was assigned for no expression of podoplanin and a grade of 1 was assigned for expression limited to the basal layer. Grades 2-4 consisted of increasing levels of expression at the basal layer with expression at more than one suprabasal layer. Primary outcome measures included proportions (%), sensitivity, negative predictive value, and hazard ratio (HR) with 95% confidence intervals (CI).
Results: 14 studies included 971 patients, with OL (N=710), OE (N= 34), OSF (N= 20), OSCC (N= 135), and normal controls (N= 72). Podoplanin expression varied between groups, with positive expression in 36.1% [95% CI: 7.9% - 71.1%] of the healthy population without OPMD, 55.5% [95% CI: 45.6% - 65.3%] of the OPMD patients, and 98.2% [95% CI: 93.1% - 99.8%] of the patients with OSCC (each pair comparison p < 0.01). In studies that provided data on podoplanin expression in OPMDs that transformed (n=7), sensitivity and negative predictive value for malignant transformation were 78.9% [95% CI: 69.7% - 86.2%] and 88.8% [84.4% - 92.1%], respectively. The hazard ratio was 4.4 for the malignant transformation of podoplanin expressing OPMDs [95% CI: 2.6-7.4].
Conclusion: Podoplanin expression increases from normal tissue, OPMD, and OSCC, respectively. Furthermore, OPMD with podoplanin expression has higher rates of malignant transformation than OMPDs not expressing podoplanin. Positive podoplanin expression can be used to stratify patients with OPMD as high risk for malignant transformation.
Keywords: Oral Pre-Malignant Disease, Malignant transformation, Risk Stratification, Oral Cavity
Level of Evidence: 2