Unravelling the molecular crosstalk between Epithelial-Mesenchymal transition and human papillomavirus in oral cancer

Oral squamous cell carcinoma (OSCC) is an extremely aggressive malignancy with intricate underlying molecular mechanisms. Emerging evidence suggests that human papillomavirus (HPV) infection, particularly its key oncogenes E6 and E7, can orchestrate epithelial-mesenchymal transition (EMT), a vital process promoting metastasis and tumor growth. HPV oncoproteins can induce EMT by affecting transcription factors like Snail, Twist, and Zeb, and EMT markers (E-cadherin, N-cadherin, and vimentin). These molecular alterations lead to increased invasiveness, stem cell-like properties, and therapeutic resistance in oral cancer, particularly, occurring in the oropharynx. In parallel, epigenetic modifications also play a crucial role in the development and progression of OSCC. Alterations like DNA methylation, histone modifications, chromatin remodelling, and non-coding RNA activity contribute to carcinogenesis by knocking down tumor suppressor genes, disrupting transcriptional regulation, and inducing genomic instability. Aberrant promoter hypermethylation and dysregulated microRNA expression not only facilitate cancer progression but also help in early detection and targeted therapies. This review explores the mechanistic link between HPV-induced EMT and epigenetic regulation in OSCC, highlighting their combined effect on tumor behaviour and therapeutic outcome. Understanding the related molecular pathways in detail could provide new insights into development of novel biomarkers and targeted therapies for HPV-associated oral cancers.