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Currently, 13 members of the Polyomaviridae family have been classified as human polyomavirus (HPyVs). Despite high seroprevalence values have been reported for the majority of the HPyVs worldwide, the main mode of transmission remains to be elucidated, and simple and common routes, such as faecal\u2010oral and respiratory have been suggested. In general, HPyVs are responsible for asymptomatic primary infection, followed by asymptomatic lifelong persistent infection. In situations of severe immunosuppression, viral reactivation of some HPyVs may occur and result in the development of associated clinical manifestations. JCPyV is the causative agent of Progressive Multifocal Leukoencephalopathy, BKPyV is associated with nephropathy among kidney transplant recipients, MCPyV with Merkel Cell Carcinoma and TSPyV with Trichodysplasia spinulosa. The association of certain HPyVs with severe diseases, in addition to the high seroprevalence of the majority of HPyVs, emphasises the need to address various knowledge gaps that still exists in the natural history of these viruses, including the transmission routes and the pathogenic mechanisms. The present review summarises current information on HPyV transmission routes and associated diseases, including diagnosis and available treatment options, highlighting the need for further studies.<\/jats:p>","DOI":"10.1002\/rmv.70166","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T15:35:16Z","timestamp":1779464116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Polyomaviruses of Clinical Relevance: Modes of Transmission and Associated Pathologies"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-095X","authenticated-orcid":false,"given":"Joana M.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy University of Coimbra CERES  Coimbra Portugal"},{"name":"Department of Life Sciences Centre for Functional Ecology (CFE) Associate Laboratory TERRA University of Coimbra  Coimbra 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