Viral carcinogenesis in skin cancer

The skin is an organ in which direct contact with viruses, solar UV irradiation and increased susceptibility to immune suppression gather to support viral tumorigenesis. Viruses transform keratinocytes by activation of cancer-promoting genes. Viral proteins may directly act as oncogenes that drive cells to proliferate or generate inflammatory responses and cause regeneration of injured cells that eventually lead to malignant transformation. Accelerated viral carcinogenesis is observed in the immune-deficient host. Decreased T-cell reactivity and lower number of antigen-presenting cells in the skin assist in viral escape and emergence of skin tumors. Three pathogenic human viruses associated with skin neoplasms are described: human papilloma virus (HPV), Kaposi's sarcoma (KS)-associated herpesvirus and human T-cell leukemia virus type 1. HPV was linked to squamous cell carcinoma (SCC) of the skin after its role in SCC of the cervix has been discovered. In the rare autosomal recessive epidermodysplasia verruciformis, an increased susceptibility to specific HPV strains initially results in widespread wart infection and later in life in the development of SCC over the sun-exposed skin. The role of HPV in nonmelanoma skin cancer of immune competent hosts is more difficult to prove. The discovery of human herpesvirus 8 as the causative pathogen of KS was made following the AIDS epidemic, and its role in all clinical variants of this tumor was confirmed. KS-associated herpesvirus exerts its tumorigenic effect through a wide repertoire of genes that regulate angiogenesis, inflammation, and cell cycle. Human T-cell leukemia virus type 1 causes adult T-cell leukemia and is often associated with skin eruptions that share common features with cutaneous T-cell lymphoma. In summary, studies of oncogenic viruses shed light on molecular mechanisms leading to tumor formation and aid in recognition of new pathways of carcinogenesis.