Background: Hepatitis D virus (HDV) is a blood-borne RNA virus classified in the Deltavirus genus, which requires hepatitis B to infect hepatocytes. Merkel cell polyomavirus (MCPyV) is a polyomavirus that is commonly acquired in early childhood by close contact between humans, and the virus persists as a major component of the normal skin virome. Human cytomegalovirus (HCMV) is a beta-herpesvirus, which can be transmitted through body fluids and from mother to foetus during pregnancy.
Objectives and Methods: A cancer hazard evaluation of the three viruses was conducted by an international Working Group of 17 experts without conflicts of interest, following the procedures described in the Preamble to the IARC Monographs. A systematic literature search was conducted, and the publicly available data on cancer in humans, cancer in experimental animals, and studies with evidence relevant for the 10 key characteristics of carcinogens were screened and summarized. The Working Group then evaluated the strength of each evidence stream and integrated these evaluations into an overall cancer hazard classification for each agent following the procedures of the IARC Monographs Preamble.
Results: The Working Group finalized their evaluations during a meeting in Lyon, France in June 2025. HDV was classified as carcinogenic to humans (Group 1) based on sufficient evidence in humans that HDV causes hepatocellular carcinoma (HCC). A consistent and strong positive association between HDV infection and increased risk of HCC was observed in cohort and case-control studies, which remained when restricted to studies that accounted for potential confounders (such as infection with human immunodeficiency virus (HIV) or hepatitis C virus, alcohol intake, and body mass index).
MCPyV was classified as carcinogenic to humans (Group 1) based on sufficient evidence in humans that MCPyV causes Merkel cell carcinoma (MCC), and on the combination of sufficient evidence for cancer in experimental animals and strong mechanistic evidence in exposed humans. A nested case-control study found a strong (five-fold) positive temporal association of MCPyV neutralising antibodies and subsequent development of MCC. This finding complemented the findings of case-control studies, as well as case series showing integration and mutations of MCPyV in MCC tumours. HCMV was classified as possibly carcinogenic to humans (Group 2B) based on limited evidence in humans that HCMV causes childhood acute lymphoblastic leukaemia (ALL). Findings of a positive association between HCMV markers and ALL were observed across studies, but concerns remained about chance and confounding.
Conclusions/Implications: The evaluations demonstrated the carcinogenicity of HDV and MCPyV which can be used as a basis to inform the development of exposure reduction strategies to reduce cancer risk. Future research may elucidate the carcinogenicity of HCMV. 
 

Infographic showing results of IARC Monographs meeting 139