Epidemiology of Merkel Cell Polyomavirus Infection and Merkel Cell Carcinoma

Simple Summary Merkel cell polyomavirus (MCPyV) is a widespread virus that is present on human skin. Infection occurs early in life, and up to 90% of adults have antibodies against MCPyV. In older persons, a rare but aggressive cancer, Merkel cell carcinoma (MCC), can develop especially on sun-exposed skin at a fast-growing as a painless red nodule. Certain risk factors for MCC development have been identified, e.g., fair skin, male sex, older age (>70 years), and immunosuppression. In recent decades, the annual number of newly diagnosed MCC per 100.000 people has risen worldwide. In 80% of cases, MCPyV is the causative agent. Another entity of MCC is caused directly by DNA damage due to UV light. Both MCC entities have low survival and high recurrence rates unless diagnosed early. To raise awareness of this uncommon cancer, the epidemiology of MCPyV and MCC, as well as the characteristics of MCC, are reviewed in this article. Merkel cell polyomavirus (MCPyV) is a ubiquitous virus replicating in human dermal fibroblasts. MCPyV DNA can be detected on healthy skin in 67-90% of various body sites, and intact virions are regularly shed from the skin. Infection occurs early in life, and seropositivity increases from 37 to 42% in 1- to 6-year-olds to 92% in adults. Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine tumor of the skin. It develops mainly on sun-exposed areas as a fast-growing, reddish nodule. Two MCC entities exist: about 80% of MCC are MCPyV-associated. Tumorigenesis is driven by viral integration into the host genome and MCPyV oncogene expression. In MCPyV-negative MCC, UV radiation causes extensive DNA damage leading to the deregulation of the cell cycle. In recent decades, MCC incidence rates have increased worldwide, e.g., in the United States, from 0.15 in 1986 to 0.7/100,000 in 2016. Risk factors for the development of MCC include male sex, older age (>75 years), fair skin, intense UV exposure, and immunosuppression. Projections suggest that due to aging populations, an increase in immunosuppressed patients, and enhanced UV exposure, MCC incidence rates will continue to rise. Early diagnosis and prompt treatment are crucial to reducing high MCC morbidity and mortality.