title: The conundrum of causality in tumor virology: the cases of KSHV and MCV.
abstract: Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch's postulates, work poorly or not at all for these viruses. Kaposi's sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology.
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, United States. Electronic address: psm9@pitt.edu.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Moore
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, United States. Electronic address: yc70@pitt.edu.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
mesh_terms: D019288:Herpesvirus 8, Human / Q000502:physiology*; D049671:History, 18th Century; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D059965:Merkel cell polyomavirus / Q000502:physiology*; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000266:history; D009858:Oncogenic Viruses / Q000502:physiology*; D014412:Tumor Virus Infections / Q000150:complications* / Q000453:epidemiology / Q000266:history
keywords: Cancer virus; Carcinogenic mechanisms; Causal inference; Causality; Kaposi's sarcoma herpesvirus; Merkel cell polyomavirus