Abstract SY34-01: Infection causing cancer: An update on the global burden
Authors: de Martel Catherine 
Published: August 2015

Abstract
Authors: Catherine de Martel1, Jérôme Vignat1, Delphine Maucort-Boulch2,3,4, Eric Engels5, Meredith Shiels5, Edgar Simard6, H Irene Hall7, Silvia Franceschi1, Martyn Plummer1
1IARC, Lyon, France, 2Department of Biostatistics, Hospices Civils de Lyon, Lyon, France 3CNRS, Laboratoire Biostatistique Sante, UMR 5558, Pierre Benite, France 4Faculte de Medecine Lyon-Sud, Universite Claude Bernard Lyon 1, Villeurbanne, France 5 National Cancer Institute, Rockville, MD, USA 6 American Cancer Society, Atlanta, GA, USA 7Centers for Disease Control and Prevention, Atlanta, GA, USA Eleven infectious agents have been classified as carcinogenic to humans (1): hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), Opistorchis viverrini, Chlonorchis sinensis, Human papillomavirus (HPV), Epstein-Barr virus (EBV), Kaposi Sarcoma herpes virus (KSHV), Helicobacter pylori, human T-cell lymphotropic virus type 1, and Schistosoma haematobium.
We estimated the global burden of cancer attributable to these infections in the year 2008 (2). Of the 12.7 million new cancer cases that occurred in 2008, 2 million (16.1%) were attributable to infectious agents. The attributable fraction was higher in less developed countries (22.9%) than in more developed countries (7.4%). Four agents - H. pylori, HBV, HCV, and HPV - were responsible for 1.9 million cases worldwide, mainly cancers of the stomach, liver, and cervix.
The general methods developed by our group to provide these estimations in large geographical areas may be replicated at a country scale to help set local priorities in cancer prevention. However, we present here a few examples of major topics where new methods or more reliable quantitative inputs are needed:
1.
Helicobacter pylori in non-cardia gastric cancer
In recent years, evidence has accumulated that immunoblot (western blot) is more sensitive for detection of anti-H. pylori antibodies than ELISA, the detection method used in our previous analysis. We therefore reviewed the literature for studies comparing the risk of developing non-cardia gastric cancer (NCGC) in cases and controls, using both ELISA and multiple antigen immunoblot for detection of H. pylori. The results from prospective studies were combined, and the new pooled estimates were applied to the calculation of the AF for H. pylori in NCGC, then to the burden of infection-related cancers worldwide.
Using the immunoblot-based data, the worldwide attributable fraction for H. pylori in NCGC increased from 74.7% to 89.0%. This implies approximately 120,000 additional cases of NCGC attributable to H. pylori infection worldwide for a total of around 780,000 cases (6.2% instead of 5.2% of all cancers) (3).
These updated estimates reinforce the role of H. pylori as a major cause of cancer and encourage urgent efforts to determine the efficacy of H. pylori eradication in gastric cancer prevention.
2.
Hepatitis viruses causing hepatocellular carcinoma
We conducted a systematic review of the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in hepatocellular carcinoma (HCC). Eligible studies reported sero-prevalence of both hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), alone and in combination, for at least 20 adult HCC cases. Studies using first-generation ELISA for HCV detection were excluded. 119 000 HCC cases were included from 50 countries in 260 studies (4).
HBV and HCV are predominant in the etiology of HCC in virtually all world areas, with a growing fraction of HCC cases attributable to HCV infection in several countries. No data were available in large parts of Africa, Eastern Europe and Central Asia. Some countries show evidence of higher prevalence of HCV in HCC since the year 2000. Estimation of the global burden of HCC attributable to HBV and HCV requires statistical modeling to impute prevalences in countries where data are unavailable.
3.
Infection-associated cancers in the HIV/AIDS population.
In our initial report in the general population, we did not provide a separate assessment of HIV to avoid double-counting of malignancies that are jointly caused by oncogenic viruses and HIV-associated immunosuppression. In the HIV/AIDS population however, a substantially greater proportion of all cancer is expected to be attributable to infection, on account of higher prevalence of infectious agents strongly associated with cancers. In addition, immunosuppression due to HIV enhances the risk of persistent infection and neoplastic progression of several known oncogenic viruses. We therefore conducted further in-depth analysis of cancer in people with HIV in the United States. Incidence rates for cancer sites associated with infections were estimated from record linkage between HIV/AIDS registries and cancer registries. Rates were applied to estimates of the population living with diagnosed HIV in the United States in 2008 to obtain the number of incident cancer cases. Infection prevalence data were derived from literature review of case series.
In the HIV population of the United States, 40% (95%CI 39-42) of cancer cases were attributable to infection compared with 4% in the general population (5). The spectrum of agents in cancer is different between HIV-infected and general population and also changes by age in the HIV-infected population. Men who have sex with men were the HIV transmission group with the highest attributable fraction (48%, 95%CI 46-50), due to the high incidence of both Kaposi sarcoma and anal cancer. The very high fraction of cancer attributable to infection in HIV-infected people points to special opportunities to prevent these cancers.
References
1. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum 2012;100:1-441.
2. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 2012;13:607-15.
3. Plummer M, Franceschi S, Vignat J, et al. Global burden of gastric cancer attributable to pylori. Int J Cancer 2015;136:487-90.
4. de Martel C, Maucort-Boulch D, Plummer M, et al. Worldwide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma. (Submitted) 2015.
5. De Martel C, Shiels M, Franceschi S, et al. Cancers attributable to infections among adults with HIV in the United States.
Citation Format: Catherine de Martel. Infection causing cancer: An update on the global burden. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY34-01. doi:10.1158/1538-7445.AM2015-SY34-01