Merkel cell carcinoma (MCC) is a rare, malignant primary neuroendocrine cancer of the skin, usually affecting elderly, white people in sun-exposed areas. This is a highly aggressive tumor with strong propensity to metastasize. Surgery and radiation therapy remain the mainstay of treatment, with no curative treatment in case of disseminated metastases. Until 2008, MCC was thought to be caused by the malignant transformation of resident Merkel cells, but no investigation of a predominant molecular pathway that could be involved in MCC pathogenesis was successful. A real revolution in MCC understanding and management occurred in 2008, when a new human polyomavirus (MCPyV) was found to be the main etiological agent of this skin cancer. Following the discovery of MCPyV, the association of MCPyV with MCC has been confirmed worldwide, with detection of MCPyV in about 80% of MCCs. At the same time it had been shown that MCPyV infection is almost ubiquitous in healthy subjects, and MCPyV is thought to be persistent resident of the skin microbiome although the route of transmission, the host cell, the viral cycle and/or latency remain unknown. Most studies suggest that there may be two subtypes of MCC: MCPyV-positive (80%) and MCPyV-negative (20%) MCCs, and various studies have reported a better prognosis associated with MCPyV infection.

The discovery of MCPyV in MCC patients opens up new therapeutic insights. The necessity and persistence of expression of MCPyV oncoproteins during MCC development make these proteins promising therapeutic targets.