Fig. 6: Models of oncogenesis for virus-associated and non-virus-associated cancers.

A Model for oncogenesis in the absence of viral infection. A normal cell accumulates driver mutations as a result of age, defective DNA repair, exogenous carcinogens, or microbiome interactions, leading under selective pressure to initiation, promotion, and progression that ends in the malignant transformation of the cell. B Model for oncogenesis in the presence of viral infection. A normal cell is infected with a virus, and a latent infection is established as a result of inadequate host immune response, potentially associated with germline MHC dysfunction or other inherited risk factors. The infected normal cell acquires somatic mutations in specific genes, such as chromatin modifiers like RNA helicases DDX3X and EIF4A1, leading to initiation, promotion, and progression that ends in the malignant transformation of the infected cell.