Diagnostic Biomarkers in Oral Verrucous Carcinoma: A Systematic Review

Oral verrucous carcinoma (OVC), a low-grade variant of oral squamous cell carcinoma (OSCC), is most frequently seen in the oral cavity. No clear etiology has been found for this lesion, but human papilloma virus, chewing betel nuts, and ultraviolet radiation are suggested as probable causes. Differential diagnosis of OVC is challenging for oral pathologists. The aim of this study was to review the molecular-based approaches for differential diagnosis of OVC. An electronic search was conducted in Medline and Scopus from January 2004 to July 2015 limited to English language publications. Published papers on verrucous carcinoma (VC) were found according to the inclusion and exclusion criteria and analyzed qualitatively. Data extraction were performed according to PRISMA statement. A total of 423 articles were reviewed; out of which, 26 articles completely fulfilled the inclusion criteria. Most of the included studies investigated proliferative and apoptotic biomarkers such as p53 and Ki67. No definite conclusion was drawn for cytoskeletal biomarkers due to variability of factors and lack of significant expression. However, it seems that cytokeratin10 (CK 10) can be useful for differentiation of OVC and benign squamous lesions. Among cell surface and extracellular matrix biomarkers tissue biomarkers, matrix metalloproteinase (MMP)-2, -9, CD31 and CD68 seem to be useful for differentiation of OVC and OSCC and glucose transporter-1 (GLUT-1) can help in differentiation of OVC from oral epithelial dysplasia. Differences among OVC, OSCC and normal epithelium in expression profiles of the investigated biomarkers help in their differential diagnosis; although, clinicohistopathological similarities among verrucous hyperplasia, noninvasive OVC and invasive well-differentiated OSCC make the diagnosis difficult. Further studies are required to better differentiate these oral lesions.