From Antigenic Drive to Clonal Autonomy: An Update on Molecular Mechanisms of HCV-Related B-Cell Lymphomagenesis

Abstract

Simple Summary Chronic hepatitis C virus (HCV) infection is a well-established risk factor for B-cell non-Hodgkin lymphoma and represents one of the best models of infection-driven cancer development. Although the introduction of antiviral therapies has markedly reduced the burden of hepatitis C, lymphomas continue to occur in some infected individuals. This is further complicated by the proportion of people living with undiagnosed HCV infection, particularly in geographical areas where access to screening/healthcare services remains limited. This review summarizes current evidence on the biological processes involved in HCV-associated lymphomagenesis, including viral persistence in lymphoid cells, chronic immune stimulation, cryoglobulinemia, and genetic and epigenetic alterations. By integrating findings from immunology, molecular biology, and hematology, we provide an updated overview of the pathways driving lymphoma development and progression. A better understanding of these mechanisms may facilitate the identification of biomarkers of disease evolution and support the development of more effective management of infection-associated lymphoid malignancies.