Infections and Cancer Biology Group
Based on evidence from epidemiological and biological studies, IARC has classified as Group 1 carcinogens six viruses associated with the origin of certain types of human cancers: Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus type 1 (HTLV-1), as well as the bacterium Helicobacter pylori. The mucosal high-risk HPV types are the etiological agents of cervical cancer as well as a subset of anogenital and head and neck carcinomas, and are responsible for about 5% of all virus-induced cancers. In addition to these infectious agents, emerging lines of evidence support the involvement of other infectious agents in human carcinogenesis. A novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was recently discovered and is associated with a rare tumour, Merkel cell sarcoma.
The cutaneous HPV types that belong to the genus beta of the HPV phylogenetic tree, together with ultraviolet irradiation, are associated with the development of non-melanoma skin cancer (NMSC) in patients affected by a rare autosomal recessive genetic disorder called epidermodysplasia verruciformis (EV). However, several findings also support their carcinogenic role in normal populations.
Many studies on oncogenic viruses have highlighted that two key events are associated with the development of cancers: (i) cellular transformation and (ii) establishment of persistent infection. Studies on specific cancer-associated viruses, e.g. mucosal high-risk HPV types, have clearly shown that the persistence of the infection promotes the accumulation of DNA damage that may lead to the inactivation of tumour suppressors or activation of cellular oncogenes, facilitating the neoplastic transformation of the infected cells.
Two complementary strategies are currently adopted by the Infections and Cancer Biology Group (ICB) to study the role of infections in human cancers:
(i) Functional studies to characterize the biological properties of specific infectious agents using in vitro and in vivo model systems
(ii) Development of laboratory assays that are being extensively used in epidemiological studies to evaluate the contribution of infections in cancer.
With regard to the functional studies, ICB′s research is focused on the characterization of the biological properties of oncoproteins from several human viruses, i.e. mucosal and cutaneous human papillomavirus (HPV) types, Merkel cell polyomavirus (MCPyV), and Epstein-Barr virus (EBV). In particular, ICB has evaluated the ability of viral oncoproteins to deregulate pathways involved in cellular transformation and immune response.
With regard to the second strategy, ICB′s efforts are focused on the development of highly sensitive diagnostic assays for many infectious agents that can be used for large-scale epidemiological studies.