Infectious causes of cancer and their detection

Abstract

Molecular techniques for identifying pathogens associated with cancer continue to be developed, including one reported recently in BMC Medical Genomics. Identifying a causal infectious agent helps in understanding the biology of these cancers and can lead ultimately to the development of antimicrobial drugs and vaccines for their treatment and prevention.

Figure 1

Continued persistent infection by a pathogen (outer circle) requires host-cell survival (red), host-cell proliferation (yellow), and evasion of the immune system by the pathogen (blue). These pathogen-driven processes are achieved via various mechanisms that interfere with normal cell physiology and are outlined in Figure 2. Alterations in these normally highly regulated pathways can lead to transforming events that have been described as the 'hallmarks of cancer' (inner circle) [2]. Accumulation of such events can lead to cancer development. Cancer is not, however, an outcome that has been specifically selected by evolution to aid pathogen survival. Rather, it is more likely an unfortunate coincidence of pathogen capabilities selected to enable successful infection. Therefore, certain infections may not necessarily cause the infected individual to develop cancer, but may be an associated risk factor (Figure adapted from [2]).

Figure 2

Infectious agents can contribute to malignant transformation by several mechanisms. These can be broadly divided into: chronic inflammation, which drives abnormal levels of cell proliferation (yellow); direct virus-induced transformation of infected cells, leading to increased cell survival (red); and immunosuppression, which allows the pathogen to evade the immune system and persist (blue). The colour coding is maintained from Figure 1. Chronic inflammation leads to the production of inflammatory cytokines as well as reactive oxygen and nitrogen oxide species (ROS and RNOS) by phagocytes at the site of infection, which can lead to DNA damage as well as cellular damage and increased cell cycling. Virus-induced transformation is caused by the actions of pathogen-encoded oncogenic proteins as well as by integration into the host genome (HPV). The transforming events outlined in this figure do not necessarily lead directly to cancer formation; for example, despite encoding similar proteins, other infectious agents do not cause cancer. The fact that some pathogens have evolved to persist without causing tumorigenesis also highlights that persistence is maybe a prerequisite for, but is on its own insufficient for, oncogenesis in humans. Immune evasion mechanisms include control of the adaptive and innate immune system, allowing avoidance of tumor surveillance. EBV, Epstein-Barr virus; HBV, human hepatitis virus B; HCV, hepatitis virus C; HIV, human immunodeficiency virus; HPV, human papillomavirus; HTLV-1, human T-lymphotropic virus 1; KSHV, Kaposi sarcoma-associated herpesvirus.