Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

In 1911, Peyton Rous from the Rockefeller Institute demonstrated that a transplantable, spontaneous, spindle cell sarcoma derived from a Plymouth Rock chicken could be virally transmitted to healthy chickens. This first known tumor virus was named Rous sarcoma virus. The discovery led to Peyton Rous being awarded the Nobel Prize in Medicine and Physiology in 1966 and to the recognition of a new paradigm in cancer research — virus-associated cancer. Since then, there has been growing interest in the role of viruses in cancer. By 1965, Tony Epstein, Yvonne Barr, and their colleagues had succeeded in establishing cell lines derived from Burkitt lymphomas and in visualizing herpesvirus-like particles, namely Epstein-Barr virus, as the first human virus linked to malignancy. Advanced molecular technology contributed to the identification of other human carcinogenic viruses such as hepatitis B virus, human papillomavirus (HPV), human T-lymphotropic virus-1, hepatitis C virus, Kaposi sarcoma-associated herpesvirus, and the most recently discovered Merkel cell polyomavirus (MCPyV) (Table 1). Most carcinogenic viruses establish persistent infections, typically occurring many years before malignancy. The viral genome is usually present in the tumor cells and is sometimes integrated into chromosomal DNA. These viruses are the etiologic agents for 15%–20% of all human tumors worldwide, and contribute to the carcinogenesis of diverse organs and tissues via central roles of cellular