Infections in the Etiology of Human Cancers Abstract: During the past century a number of chemical and physical risk factors for human cancers have been identified. Only relatively recently, mainly during the past 30 years, infectious agents have been identified as important human carcinogens. Besides a larger number of viral infections identified as risk factors for divergent and in part highly prevalent human cancers, also bacteria and parasites play a significant role. The bacterium Helicobacter pylori represents a major cause of gastric cancer, parasitic infections cause bladder (Schistosoma haematobium) and liver cancers (liver flukes). Remarkable differences exist in the mechanism of cancer induction between individual potentially carcinogenic iinfections. Some viruses (High risk papillomaviruses, Epstein-Barr virus, Kaposi’ sarcoma virus, Merkel cell polyomavirus and human T-lymphotropic retrovirus act as direct carcinogens. Here persistence and expression of specific viral oncogens are required for the maintenance of the malignant phenotype of the infected cells. Replication incompetence emerges as a major factor for the carcinogenic function of this group of agents. Other infections contribute to malignant transformation indirectly, e.g. human immunodeficiency viruses by immunosuppression, commonly followed by the activation of other latent potentially tumorigenic viruses. Alternatively, induction of chronic inflammations, resulting in the production of oxygen and nitrogen radicals seems to result in random genetic and epigenetic modifications of the host cell genome with the eventual outcome of malignant growth. The number of required geneic or epigenetic modifications in host cell genes seems to determine the long latency periods between primary infection and cancer occurrence, frequently covering several decades. Although we can presently link more than 20% of the global cancer incidence to infectious events, some data will be summarized suggesting a role of infectious agents in additional common human cancers. References: H. zur Hausen. Infections Causing Human Cancer. Wiley-VCH, Weinheim/New York (Publ.), pp. 1-517, 2006. H. zur Hausen. The search for infectious agents of human cancers: where and why. Nobel lecture. Virology, 392: 1-10, 2009.