Cancer Microbiology

Abstract

Microbes play important roles in cancer from direct carcinogenic effects to their use in treatment. Cancers caused by microorganisms account for approximately 15% of cancers, primarily in low- and middle-income countries. Unique features of infectious carcinogens include their transmissibility, mutability, and specific immune interactions, which provide challenges and opportunities for cancer prevention and treatment. For these agents, infection control through exposure reduction, antivirals, antibiotics, and vaccines is cancer control. In addition, developing evidence suggests that microorganisms including the human microbiome can indirectly modulate cancer formation and influence the effectiveness and toxicity of cancer treatments. Finally, microorganisms themselves can be used to prevent or treat cancer. The convergence of these factors signals the emergence of a new field, cancer microbiology. Recognition of cancer microbiology will spur research, stimulate cross-disciplinary training, inform drug development, and improve public health.

Figure 1.

Global distribution of cancers associated with infectious agents. The figure shows a world map and the fraction of cancers in 2012 attributable to infections (1). This figure is reprinted from Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health. 2016;4(9):e609-16, with permission from Elsevier.

Figure 2.

Infectious agents and cancer. The figure summarizes in schematic form the many ways infectious microorganisms may enhance cancer formation and how various interventions can suppress cancer formation.

Figure 3.

Unique features of carcinogenic microorganisms. Schematic diagram of key ways infectious carcinogens differ from classic physical or chemical carcinogens: they can be transmitted between hosts; they can expand and spread; they can mutate and evolve; they can specifically modulate the immune and inflammatory response and vice versa; and infections can be prevented or cured by public health measures including vaccination or medical treatments, resulting in reduced cancer risk.

Figure 4.

Historic and projected cancer burden in the HIV-infected population. The graph shows marked decrease in AIDS-defining cancers (ADCs) in the United States with the widespread adoption of antiretroviral therapy, with little change in the number of non-AIDS-defining cancers (NADCs), including lung cancer, the most common NADC. Data were extracted from Shiels et al. (24).

Figure 5.

Effect of the microbiome on the hallmarks of cancer. The outer circle shows the 10 hallmarks of cancer defined by Hanahan and Weinberg (43). The center shows the effects of specific bacteria or their toxins on these hallmarks (44). This figure is reprinted from Fulbright LE, Ellermann M, Arthur JC. The microbiome and the hallmarks of cancer. PLoS Pathog 2017;13(9): e1006480. doi.org/10.1371/journal.ppat.1006480. BFT = Bacteroides fragilis toxin; FadA = Fusobacterium nucleatum adhesion protein; Fap2 = Fusobacterium nucleatum surface protein; pks+ E. coli = colibactin-producing E. coli; TLR = Toll-like receptor.

Figure 6.

Prevention of hepatocellular cancer by vaccination and antiviral treatments. A) Hepatitis B virus (HBV) vaccination reduces the incidence of hepatocellular carcinoma. Graph shows reduction in the incidence of hepatocellular carcinoma (HCC) in individuals vaccinated against HBV compared with unvaccinated (control) individuals (106). This figure is modified from Qu C, Chen T, Fan C, Zhan Q, Wang Y, et al. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong Hepatitis B intervention study: a cluster randomized controlled trial. PLoS Med. 2014;11(12): e1001774. 10.1371/journal.pmed.1001774. B) Direct acting antiviral drugs that cure hepatitis C virus (HCV) infection reduce the incidence of hepatocellular carcinoma. Graph shows reduction in the incidence of HCC in treated individuals displaying a sustained anti-HCV response to antiviral therapy (SVR) compared with treated individuals who did not display SVR. This figure is modified from Ioannou et al. (107), with permission from Elsevier.