A Review on the Role of Vascular Endothelial Growth Factor Receptors in Human Papillomavirus-related Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a neoplasm at the epithelial lining of the oral cavity that is prevalent worldwide. Smoking tobacco and consumption of alcohol are the main risk factors for OSCC. However, human papillomavirus (HPV) could also be an aetiological factor for OSCC. Transmission through urogenital contact increases the risk of developing OSCC, especially in developed countries. HPV-related cancer displays different pathogenesis and clinical outcomes. HPV through its oncogene E6 and E7 play a critical role in carcinogenesis by disrupting the DNA repair mechanism and cell cycle. Increased expression of VEGF ligand in HPV-related cancer has been reported in numerous studies. In OSCC, VEGFRs, i.e., VEGFR-1, VEGFR-2, and VEGFR-3, are overexpressed, with a higher expression on VEGFR-2. In HPV-infected OSCC, HPV is associated with VEGF expression. However, VEGFRs show no such association. This review highlights the possible role of angiogenesis in the progression of HPV-related OSCC. Also, it discusses how VEGF/VEGFR regulated the angiogenic activity caused by the HPV infection. Data on VEGF/VEGFR associated with HPV status is limited, and their role in OSCC progression remains unclear. Elucidating the mechanism of angiogenesis in HPV-associated OSCC may help develop strategies for OSCC-targeted therapy.