Infection and cancer in multicellular organisms

Abstract

Evolutionary considerations suggest that oncogenic infections should be pervasive among animal species. Infection-associated cancers are well documented in humans and domestic animals, less commonly reported in undomesticated captive animals, and rarely documented in nature. In this paper, we review the literature associating infectious agents with cancer to evaluate the reasons for this pattern. Non-malignant infectious neoplasms occur pervasively in multicellular life, but oncogenic progression to malignancy is often uncertain. Evidence from humans and domestic animals shows that non-malignant infectious neoplasms can develop into cancer, although generally with low frequency. Malignant neoplasms could be difficult to find in nature because of a low frequency of oncogenic transformation, short survival after malignancy and reduced survival prior to malignancy. Moreover, the evaluation of malignancy can be ambiguous in nature, because criteria for malignancy may be difficult to apply consistently across species. The information available in the literature therefore does not allow for a definitive assessment of the pervasiveness of infectious cancers in nature, but the presence of infectious neoplasias and knowledge about the progression of benign neoplasias to cancer is consistent with a widespread but largely undetected occurrence.

Peto's paradox and the promise of comparative oncology

“…The Ewalds [45] show that one regularity across species is the fact that infectious agents often cause neoplasms. This can be seen in the galls and boils in plants as well as many of the cancers reported in zoos and domesticated animals.…”

Short‐ and long‐term evolution in our arms race with cancer: Why the war on cancer is winnable

“…But approximately 15% of all human cancers worldwide are known to be caused by pathogens (Lunn, Jahnke, & Rabkin, ; Plummer et al., ), and some observers suggest the true figure may prove to be higher (Ewald & Swain Ewald, ). Pathogens are more different biochemically from healthy human cells than are human tumor cells, offering greater opportunities for selective toxicity (Ewald & Swain Ewald, , ), as well as more abundant preventive approaches to cancer (e.g., vaccination). Capitalizing on these opportunities, advances in the treatment some pathogen‐associated cancers are beginning to reduce cancer incidence and mortality (Casper & Fitzmaurice, ; Ewald & Swain Ewald, ; Global Burden of Disease Cancer Collaboration ; Plummer et al., ).…”

“…Inflammation increases cancer risk through several pathways, including by enhancing production of reactive oxygen and nitrogen species that damage DNA and producing various proliferative signals (Alibek, Kakpenova, & Baiken, ; Brennan & Garrett, ; Ewald & Swain Ewald, ; Graham, ). Immune suppression disrupts immune surveillance of cancer, resulting in broad increases in cancer risk (e.g., Schistosoma spp., HIV; Ewald & Swain Ewald, , , , ). The fitness of these pathogens is not directly enhanced by neoplasia in their host.…”

“…Furthermore, the finding that many tumor cells host only latent or “pseudolatent” viruses that are not actively replicating (Chang et al., ) suggests that viral evolution may not strongly oppose anticancer treatments. Once the cancer progresses to threaten host survival, the evolutionary interests of the cancer cells and the oncogenic virus are no longer well aligned (Chang et al., ; Ewald & Swain Ewald, ) and the reproductive value of viruses remaining in the host will be low; thus, oncogenic viruses may not strongly oppose treatments of metastatic cancer, especially if they arrest cancer development rather than creating an outright cure.…”

Transmissible cancers, are they more common than thought?

“…Although many cancers are associated with infectious agents (Ewald and Swain Ewald ), only four naturally occurring transmissible cancers have so far been identified in dogs, soft‐shell clams and Tasmanian devils (DFT1 and DFT2) (Pye et al. ).…”