Merkel Cell Polyomavirus (MCPyV) and Its Possible Role in Head and Neck Cancers

Despite significant progress in its prevention, diagnosis, and treatment, head and neck cancer (HNC) remains a major global health issue due to its multifactorial pathogenesis. Indeed, HNCs have been found to be associated with different environmental and lifestyle factors, as well as with infection with oncogenic viruses. To date, seven viruses are recognized for their tumorigenic properties and have been proposed as implicated in HNC development, including Merkel Cell Polyomavirus (MCPyV). MCPyV is well recognized as the major etiological agent of Merkel cell carcinoma (MCC), a rare but rapidly metastasizing skin neoplasm. Specifically, in almost 80% of MCC cases, viral genome integration occurs, and a truncated form of Large T Antigen (tLT) is expressed. Although MCC is a rare cancer, MCPyV is a ubiquitous virus, widely distributed among the human population. Therefore, a plausible role of the virus has been proposed, even for other tumors. The current review provides an overview of the available data describing the presence of MCPyV in non-MCC tumors, such as HNCs, with the aim of elucidating the potential contribution of MCPyV to oral cancer. Understanding the role of viral infections in the etiology of cancer opens up the opportunity for developing preventive measures and targeted therapies that effectively address HNC progression while reducing treatment-related side effects.