Joint Infectious Causation of Human Cancers

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., ).…”

“…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., ). But, might the evolutionary continuity within pathogen populations cause our arms race with these cancers to unfold in a qualitatively different, and more adverse, way?…”

“…Second are pathogens, most of which are extracellular, that cause cancer largely by eliciting chronic inflammation or immune suppression in their host. 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, , , , ).…”

Infection and cancer in multicellular organisms

“…The means by which trematode parasites contribute to human cancer have been presumed to be through induction of inflammation [52]. Recent work suggests, however, that the two human cancers caused by trematodes (table 1) may involve joint infectious causation with viruses: hepatitis B and C viruses for cholangiosarcoma and human papillomaviruses for bladder cancer (reviewed by Ewald & Swain Ewald [51]). The trematode infections may thus be exacerbating viral causation in these cancers through oncogenic effects of inflammation.…”

“…The selection for increased propagation through host cell proliferation does not apply to extracellular parasites. In this regard, the mechanism by which Helicobacter pylori contributes to human cancer (table 1) is still unclear, although it does involve the compromising of host barriers to cancer to some extent [51]. The means by which trematode parasites contribute to human cancer have been presumed to be through induction of inflammation [52].…”