Human Papillomavirus (HPV) Infection-Associated Epithelial-to-Mesenchymal Transition: Implication in Tumorigenesis and Pathogenesis of HPV-Positive Cancers

Epithelial-to-mesenchymal transition (EMT) is a programmed and reversible process that allows epithelial cells to temporarily acquire a mesenchymal cell phenotype with increased migratory and invasive capacity. Analogous phenotypic modulation can also occur in carcinoma cells, which, after undergoing EMT, exhibit cancer stem cell-like properties and actively migrate, leading to tumor invasion and metastases. This structured narrative review focuses on the molecular crosstalk between human papillomavirus (HPV) and EMT, which occurs in HPV-infected human epithelium and in HPV-positive cancers of different location (cervical, head and neck, colorectal, lung, and others). The main questions addressed here are: (i) how HPV-driven EMT may contribute to the malignant transformation of HPV-infected epithelial cells, (ii) what mechanistic links may exist between the HPV positivity and EMT in human cancers, and (iii) how EMT in various HPV-positive human tumors may influence their pathogenesis, treatment modalities and outcomes. The relationship between HPV infection and EMT program is delineated as a complex multicomponent mechanism triggered by exogenous and endogenous stimuli and involving specific ligand-receptor interactions, membrane channels, transcription factors, signaling pathways, epigenetic regulators, etc. The review also discusses some of the potential applications of EMT-related biomarkers and molecular targets in the prevention, prediction and treatment of HPV-induced cancers.