Infection-Associated Cancers

Socioeconomic development associated with a decrease in infection-associated cancers

According to an article published on 25 July 2016 in the Lancet Global Health, of 14 million new cancer cases in 2012, 15.4% were attributable to carcinogenic infections. Two-thirds of infection-attributable cancers occurred in less developed countries, in which infections accounted for nearly one in four cancers.

The most important infectious agents worldwide were Helicobacter pylori, human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV). Kaposi's sarcoma was the second largest contributor to the cancer burden in sub-Saharan Africa.

Contribution of carcinogenic infections to the global burden of cancer has been periodically assessed. Evidence on the association between infection and cancer was comprehensively reviewed by an expert working group of the International Agency for Research on Cancer (IARC) in 2009. On the basis of these expert reviews, they published estimates of the global burden of cancer due to infection for the year 2008.

Since then, new cancer incidence estimates have become available from GLOBOCAN for the year 2012 and from many new epidemiological studies better evidence on the involvement of HPV in cancers of the head and neck and Helicobacter pylori in gastric cancer, notably gastric cardia cancer. In the latest study, the IARC researchers synthesised the available data to present an updated picture of cancer and infection burden worldwide, improving on the previous report by using the most recent data and giving more details of individual country estimates and analysis by level of socioeconomic development.

Infections with certain viruses, bacteria, and parasites are strong risk factors for specific cancers. 11 infectious agents have been classified as well established carcinogenic agents in human beings by the IARC: Helicobacter pylori, HBV, HCV, HIV type 1, HPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59—known collectively as high-risk types), EBV, human herpesvirus type 8 (HHV-8; also known as Kaposi's sarcoma herpesvirus), human T-cell lymphotropic virus type 1 (HTLV-1), Opisthorchis viverrini, Clonorchis sinensis, and Schistosoma haematobium.

Among these agents, HIV is unique in attributable risk calculations because it has been shown to increase cancer risk only in combination with other carcinogenic infectious agents; therefore, the IARC researchers chose to attribute cancers in HIV-positive people to the co-infection.

Therefore, they considered 10 infectious agents other than HIV and the associated cancer types as following:   

Helicobacter pylori - non-cardia gastric carcinoma, gastric cardia carcinoma, gastric non-Hodgkin’s lymphoma

HBV - liver cancer

HCV - liver cancer, non-Hodgkin’s lymphoma

HPV - cervical carcinoma, penile carcinoma, anal carcinoma, vulvar carcinoma, vaginal carcinoma, carcinoma of the oropharynx, including tonsils and base of tongue, cancer of the oral cavity, laryngeal cancer

EBV - Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma

HHV-8 - Kaposi’s sarcoma

HTLV-1 - adult T-cell leukaemia and lymphoma

Opisthorchis viverrini and Clonorchis sinensis - bile duct cancer

Schistosoma haematobium - bladder cancer.

In 2012, around one sixth of cancer cases worldwide were attributable to infectious agents. Two-thirds of infection-attributable cancers occurred in less developed countries, in which infections accounted for nearly one in four cancers. The main infectious agents contributing to the cancer burden were Helicobacter pylori, HPV, HBV, and HCV, which together accounted for 92% of all infection-attributable cancers worldwide.

The attributable friction for infection varied by country and development status—from less than 5% in the USA, Canada, Australia, New Zealand, and some countries in western and northern Europe to more than 50% in some countries in sub-Saharan Africa.

The authors emphasized that a large potential exists for reducing the burden of cancer caused by infections. Socioeconomic development is associated with a decrease in infection-associated cancers; however, to reduce the incidence of these cancers without delay, population-based vaccination and screen-and-treat programmes should be made accessible and available.

An associated comment emphasize that the proportion of cancers caused by infectious agents is likely to be under-represented in this analysis. Increased efforts and focus on vaccine development are of paramount importance. Other strategies to reduce the incidence of infection-related cancers are also worthy of consideration and behavioural or public health interventions to reduce incident cancer-associated infections. With the availability of vaccines, screen-and-treat approaches, and effective drugs to treat HCV, Helicobacter pylori, and HIV infections, the question is no longer limited to what to do but now extends to how to implement.

The expanding focus from basic research, drug development, and clinical trials that are historically concentrated in high-income countries, to the efforts in collaboration with centres in endemic areas, has the potential to both reduce the burden of infection-related cancers and shed light on presently unknown pathways in carcinogenesis.

References

Plummer M, de Martel C, Vignat J, et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Oncology 2016;Published Online 25 July. DOI: http://dx.doi.org/10.1016/S2214-109X(16)30143-7

Casper C, Fitzmaurice C. Infection-related cancers: prioritising an important and eliminable contributor to the global cancer burden. Lancet Global Health 2016; Published Online 25 July. DOI: http://dx.doi.org/10.1016/S2214-109X(16)30169-3