Merkel cell polyomavirus and non-Merkel cell carcinomas: Guilty or circumstantial evidence?

Abstract

Merkel cell polyomavirus (MCPyV) is the major causative factor of the rare but aggressive cancer, Merkel cell carcinoma (MCC). Two characteristics of MCPyV‐positive MCCs are integration of the viral genome and expression of a truncated version of one of its oncogenic proteins, namely large T antigen. The strong association of MCPyV with MCC development has incited researchers to further investigate a possible role of this virus in other cancers. However, many of the examples displaying the presence of the virus in the various non‐MCC cancers are not able to clearly demonstrate a direct connection between cellular transformation and the presence of the virus. The prevalence of the virus is significantly lower in non‐MCC cancers compared to MCCs, with a lower level of viral load and sparse viral protein expression. Moreover, the state of the viral genome, and whether a truncated large T antigen is expressed, has rarely been investigated. Nonetheless, considering the strong oncogenic potential of MCPyV proteins in MCC, the plausible contribution of MCPyV to transformation and cancer growth in non‐MCC tumors cannot be ruled out. Furthermore, the absence of MCPyV in cancers does not exclude a hit‐and‐run mechanism, or the oncoproteins of MCPyV may potentiate the neoplastic process mediated by co‐infecting oncoviruses such as high‐risk human papillomaviruses and Epstein–Barr virus. The current review is focusing on the available data describing the presence of MCPyV in non‐MCC tumors, with an aim to provide a comprehensive overview of the corresponding literature and to discuss the potential contribution of MCPyV to non‐MCC cancer in light of this.