Infections are an important cause of many cancers worldwide, especially in economically transitioning countries.
Infectious agents are responsible for an estimated 15% of all new cancer cases annually worldwide, of which two-thirds occur in less developed countries (where they account for up to one quarter of all cancer). (Figure 1)
Figure 1. Proportion of cancers attributable to infections (%), by agent and region. In sub-Saharan Africa, 15.9% of cancers are attributable to human papillomavirus; 2.5% to Helicobacter pylori; 3.1% to hepatitis B virus; 1.5% to hepatitis C virus; 1.8% to Epstein-Barr virus; 5.9% to human herpesvirus-8; and 0.5% to other infections. In Eastern Asia (including China), 3.1% of cancers are attributable to human papillomavirus; 9.7% to Helicobacter pylori; 7% to hepatitis B virus; 1.6% to hepatitis C virus; 1.3% to Epstein-Barr virus; 0% to human herpesvirus-8; and 0.1% to other infections. In Central Asia (including India), 11.6% of cancers are attributable to human papillomavirus; 4.9% to Helicobacter pylori; 1.3% to hepatitis B virus; 0.7% to hepatitis C virus; 0.8% to Epstein-Barr virus; 0% to human herpesvirus-8; and 0% to other infections. In Pacific Islands, 11.3% of cancers are attributable to human papillomavirus; 2.6% to Helicobacter pylori; 3.4% to hepatitis B virus; 1.4% to hepatitis C virus; 0.4% to Epstein-Barr virus; 0% to human herpesvirus-8; and 0% to other infections. In Latin America, 7.2% of cancers are attributable to human papillomavirus; 4.7% to Helicobacter pylori; 0.8% to hepatitis B virus; 1% to hepatitis C virus; 0.5% to Epstein-Barr virus; 0.2% to human herpesvirus-8; and 0% to other infections. In North Africa and West Asia, 2.3% of cancers are attributable to human papillomavirus; 3.6% to Helicobacter pylori; 1% to hepatitis B virus; 3.4% to hepatitis C virus; 1.8% to Epstein-Barr virus; 0.2% to human herpesvirus-8; and 0.7% to other infections. In Europe, 2.5% of cancers are attributable to human papillomavirus; 3.2% to Helicobacter pylori; 0.4% to hepatitis B virus; 0.8% to hepatitis C virus; 0.3% to Epstein-Barr virus; 0.1% to human herpesvirus-8; and 0% to other infections. In North America, 1.8% of cancers are attributable to human papillomavirus; 1% to Helicobacter pylori; 0.2% to hepatitis B virus; 0.7% to hepatitis C virus; 0.3% to Epstein-Barr virus; 0.1% to human herpesvirus-8; and 0% to other infections. In Australia/New Zealand, 1.3% of cancers are attributable to human papillomavirus; 1.1% to Helicobacter pylori; 0.5% to hepatitis B virus; 0.4% to hepatitis C virus; 0.3% to Epstein-Barr virus; 0% to human herpesvirus-8; and 0% to other infections. Worldwide, 4.5% of cancers are attributable to human papillomavirus; 5.5% to Helicobacter pylori; 3% to hepatitis B virus; 1.2% to hepatitis C virus; 0.9% to Epstein-Barr virus; 0.3% to human herpesvirus-8; and 0.1% to other infections.
The four most important cancer-causing infections worldwide are Helicobacter pylori (770,000 cases globally in 2012), human papillomavirus (HPV) (640,000), hepatitis B virus (HBV) (420,000), and hepatitis C virus (HCV) (170,000), which together account for more than 90% of all infection-related cancers. (Figure 2)
Figure 2. Leading cancer-causing infections worldwide, by sex (%). Among infection-attributable cancers in females, 53.6% are due to human papillomavirus; 25.1% to Helicobacter pylori; 10.7% to hepatitis B virus; 5.1% to hepatitis C virus; and 5.5% to other agents. Among infection-attributable cancers in males, 46.1% are due to Helicobacter pylori; 27.3% to hepatitis B virus; 10.3% to hepatitis C virus; 10.6% to other agents; and 5.6% to human papillomavirus.
Helicobacter pylori causes 90% of stomach cancers, half of which occur in China alone. HPV infection is a necessary cause of cervical cancer, which is the leading cause of cancer death among women in many less-developed regions of the world because of lack of screening. HPV infection is also responsible for a proportion of vulvar (25%), vaginal (78%), anal (88%), penile (50%), oropharyngeal (31% on average, but much higher in North America and Northern Europe), oral cavity (2.2%) and laryngeal cancer (2.4%). (Figure 3)
Figure 3. Most common infection-attributable cancers worldwide. 35% of all infection-attributable cancers worldwide are stomach cancer; 27% are liver cancer; 24% are cervical cancer; 5% are head and neck cancer; 4% are other anogenital cancer; and 5% are other cancer sites.
One woman dies of cervical cancer every two minutes, making it one of the greatest threats to women's health... But it doesn't have to be this way. Cervical cancer is one of the most preventable and treatable forms of cancer.
Worldwide, HBV and HCV infections account for 56% and 20% of liver cancer deaths, respectively. However, these proportions substantially vary by region, with HBV the predominant cause of liver cancer in less developed countries (2/3 of cases) and HCV in more developed settings (44%). Other infections that cause cancer include Epstein-Barr virus (120,000 cases, estimated conservatively), Kaposi sarcoma-associated herpesvirus (HHV-8; 40,000 cases, mainly in sub-Saharan Africa), human T-cell lymphotropic virus, liver flukes, and schistosomal infections. Human immunodeficiency virus (HIV) infection also indirectly causes infection-related cancers through immunodepression. In the US, for instance, the proportion of infection-associated cancer in people with HIV (40%) is 10 times larger than in the general US population (4%).
Powerful prevention tools exist for infection-related cancer, including HPV and HBV vaccines, screening for HPV-driven cervical precancer, and drugs to treat HBV, HCV, Helicobacter pylori, and HIV infections.
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HPV infection causes virtually all cervical cancers. HPV vaccines can protect against the types of HPV that cause about 90% of all cervical cancers.
Cancer in sub-Saharan Africa related to infection:
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 Sep;4(9):e609-16.
Text:
de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017 Aug 15;141(4):664–670.
de Martel C, Shiels MS, Franceschi S, et al. Cancers attributable to infections among adults with HIV in the United States. AIDS. Oct 23 2015;29(16):2173–2181.
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 Sep;4(9):e609-16.
Map & Figures 1-3:
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 Sep;4(9):e609-16. Licence CC BY-NC-ND 4.0
Figure 3:
Notes: Stomach includes cardia, non-cardia, and NHL of gastric location. Liver includes cholangiocarcinoma. Other anogenital includes vulva, vagina, penile, and anus. Head and neck includes oropharynx, nasopharynx, oral cavity, and larynx. Other includes Hodgkin lymphoma, non-Hodgkin lymphoma, Burkitt adult T cell lymphoma, Kaposi sarcoma, and bladder.