Kaposi Sarcoma–Associated Herpesvirus-Associated Malignancies: Epidemiology, Pathogenesis, and Advances in Treatment

Kaposi sarcoma associated herpesvirus (KSHV), a γ2-herpesvirus, also known as human herpesvirus-8, is the etiologic agent of three virally associated tumors: Kaposi sarcoma, a plasmablastic form of multicentric Castleman disease (KSHV-MCD), and primary effusion lymphoma. These malignancies are predominantly seen in people with acquired immunodeficiencies, including acquired immunodeficiency syndrome and iatrogenic immunosuppression in the setting of organ transplantation, but can also develop in the elderly. Kaposi sarcoma (KS) is most frequent in regions with high KSHV seroprevalence, such as sub-Saharan Africa and some Mediterranean countries. In the era of combination antiviral therapy, inflammatory manifestations associated with KSHV-infection, including KSHV-MCD, a recently described KSHV-associated inflammatory cytokine syndrome and KS immune reconstitution syndrome also are increasingly appreciated. Our understanding of viral and immune mechanisms of oncogenesis continues to expand and lead to improved molecular diagnostics, as well as novel therapeutic strategies that employ immune modulatory agents, manipulations of the tumor microenvironment, virus-activated cytotoxic therapy, or agents that target interactions between specific virus-host cell signaling pathways. This review focuses on the epidemiology and advances in molecular and clinical research that reflects the current understanding of viral oncogenesis, clinical manifestations, and therapeutics for KSHV-associated tumors.