Download Infectious causes of cancer factsheet

FACT SHEET
Infectious causes of cancer
KEY MESSAGES
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3.3% of all cancers in Australia can be attributed to infectious agents.
Cancers caused by infectious agents are more prevalent in developing regions of the
world.
Infections that cause cancer are common among humans. However, most people’s
immune systems will clear these infections. It is chronic infection with viruses,
bacteria, and parasites that leads to the development of cancer in a small proportion
of the population.
All cervical cancer, adult T-cell leukaemia/lymphomas, and Kaposi’s sarcomas can
be attributed to an infectious agent.
Effective vaccinations are available for human papillomavirus strains responsible for
most of cervical cancer, and the hepatitis B virus.
Effective antiviral treatments have been developed for hepatitis B virus, human
immunodeficiency virus 1, and hepatitis C virus.
Infections and Cancer
In 2008, about 2 million new cases of cancer worldwide were attributed to infections by
certain viruses, bacteria, and parasites.1 This equates to approximately 16% of all cancers
worldwide.1 As can be seen in Table 1, the proportion is higher in developing countries,
where 23% of all cancers were attributed to infections, and lower in developed countries,
where 7.4% of cancers were attributed to infectious causes.1 In Australia this proportion was
estimated to be even lower, at 3.3% of all cancers.1
Table 1: Number of new cancer cases globally in 2008 attributable to infectious
agents, by cancer type.
Cancer Type
Number of
new cancer
cases
Number of new
cancer cases
attributable to
infection in
less developed
regionsα
Number
attributed to
infection in
more
developed
regionsβ
PAF* (%)
Non-cardia gastric
870 000
470 000
180 000
74.4%
Liverφ
750 000
510 000
69 000
76.9%
Cervix uteri
530 000
450 000
77 000
100.0%
Vulva
27 000
4 100
7 500
43.0%
Anus
27 000
12 000
12 000
88.0%
Penis
22 000
7 600
3 200
50.0%
Carcinoma
1
Vagina
13 000
5 700
3 400
70.0%
Oropharynx
85 000
6 400
15 000
25.6%
Nasopharynx
84 000
66 000
5 900
85.5%
260 000
6 000
0
2.3%
Hodgkin’s
68 000
23 000
10 000
49.1%
Non-Hodgkin’s
gastric
18 000
6 500
6 700
74.1%
Burkitt
11 000
6 300
530
62.5%
360 000
18 000
11 000
8.2%
2 100
660
1 500
100.0%
43 000
39 000
4 100
100.0%
3 200 000
1 600 000
410 000
64.4%
Bladder
Lymphoma and leukaemia
Hepatitis C virus
associated nonHodgkin
Adult T-cell
leukemia/lymphoma
Kaposi’s sarcoma
Total infectiousdisease related sites
α Less developed regions = Africa; Caribbean; Central America; South America; Asia excluding
Japan; and Oceania excluding Australia and New Zealand.
β More developed regions = Australia and New Zealand; Europe; Japan; and Northern America.
*PAF = Population attributable fraction. Estimate of the proportion of cases of cancer that could be
avoided if exposure to the infectious agent were modified or removed.
φ Including cholangiocarcinoma.
Source - de Martel et al Lancet Oncology 2012
The types of viruses, bacteria and parasites that are linked to cancer are common in the
normal healthy population, worldwide. Most people’s immune systems will clear these
infections quickly. It is chronic infection with these viruses, bacteria and parasites that leads
to cancer development. It is however rare for an infection to develop into cancer. The many
ways in which chronic infections lead to cancer are not fully understood. There is evidence to
suggest that infections lead to cancer either directly, through accumulation of DNA damage
(viral DNA integrating itself into the human DNA) or through chronic inflammation causing
cells to rapidly divide. Evidence also suggests that infections can lead to cancer indirectly,
through chronic suppression of the immune system, or tissue damage caused by the
immune system’s attempts to fight off infection.2-4 Table 1 also illustrates that for cervical,
adult T-cell leukemia/lymphoma, and Kaposi’s sarcoma, all cancers can be attributed to their
respective infectious causes. However, for others, such as bladder cancer only a small
proportion of cancers are attributed to infectious causes.1
Table 2 presents the infectious agents that the International Agency for Research on Cancer
(IARC) have classified as either carcinogenic (cancer causing) or probably carcinogenic
(contributing to cancer development) in humans. IARC is a part of the World Health
2
Organization which convenes international expert working groups to evaluate the evidence
of the carcinogenicity of specific exposures.
Table 2: Infectious agents that are carcinogenic or probably carcinogenic to humans
Infectious agent
Associated cancers
Epstein-Barr virus
Burkitt lymphoma
Hodgkin lymphoma
Non-Hodgkin lymphoma
Nasopharyngeal carcinoma
NK/T-cell lymphoma
Hepatitis B virus
Hepatocellular carcinoma (a type of liver
cancer)
Hepatitis C virus
Hepatocellular carcinoma (including
cholangiocarcinoma, which is a type of liver
cancer)
Non-Hodgkin lymphoma
Human papillomavirus types 16, 18, and
others
Anal cancer
Cervical cancer
Oral cancer
Oropharyngeal cancer (cancer of the base
of the tongue, tonsils, or upper throat)
Penile cancer
Vaginal cancer
Vulvar cancer
Human immunodeficiency virus 1
Anal cancer
Cervical cancer
Conjunctiva cancer (in the eye)
Hodgkin lymphoma
Kaposi sarcoma
Non-Hodgkin lymphoma
Human T-cell lymphotropic virus 1
Adult T-cell leukemia/lymphoma
Kaposi sarcoma herpesvirus/ human
herpesvirus 8
Kaposi sarcoma
Primary effusion lymphoma
Helicobacter pylori (bacterium)
Non-cardia gastric carcinoma
B-cell MALT gastric cancer
Opisthorchis viverrini and Clonorchis sinensis
(parasites)
Cholangiocarcinoma
Schistosoma haematobium (parasite)
Bladder cancer
Source - IARC Mongraph Vol 100B, 2012
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The infectious agents responsible for the majority of infection-related cancers are:
Helicobacter pylori (H. pylori); cancer-causing strains of the human papillomavirus (HPV);
and the hepatitis B and C viruses. These four infectious agents alone cause more than 15%
of all cancers globally.2
In addition, Merkel cell polyomavirus (MCV) is a common human tumour virus. MCV is a
major risk factor for Merkel cell carcinoma (MCC), a rare but aggressive type of skin cancer,
most common in elderly and immune suppressed people. A 2008 study found that MCV
causes approximately 80% of MCCs.5
Epstein Barr Virus
Epstein-Barr Virus (EBV) is most commonly transmitted by oral exposure (for example prechewing food for infants or transfer via saliva). Whereas almost every adult has been
exposed to EBV at some point in their lives, in very rare circumstances it can cause certain
types of lymphoma.6 Immuno-suppressed organ transplant patients with EBV infection have
an increased risk of developing certain post-transplant lymphomas. EBV is also strongly
linked to Burkitt lymphoma, a common childhood cancer in equatorial Africa and Papua New
Guinea.6 Hodgkin’s lymphoma is associated with EBV worldwide, with EBV genome
detected in up to 50% of Hodgkin’s Lymphoma cases in western countries. Nasopharyngeal
carcinoma is a type of cancer most common in South East Asia, however all cases
worldwide are associated with EBV, suggesting that this virus is key to cancer development.6
Hepatitis B and hepatitis C
Globally, hepatitis B virus (HBV) is one of the most common infectious viruses. HBV is highly
contagious and is transmitted via exposure to infected blood, semen, vaginal fluid and
saliva.6 Hepatitis C virus (HCV) is transmitted via exposure to blood and blood products.6
Infection with HBV and HCV are established risk factors for liver cancer6 and these two viral
infections cause the majority of cases of liver cancer in Australia. Vaccination against HBV is
recommended for all babies and adolescents in Australia,7 and for certain high-risk adults,
e.g., immigrants from areas with high rates of Hepatitis B, people who have unprotected sex
with multiple partners and people who inject drugs who share injecting equipment.8
Currently there is no vaccination available for HCV.9 Safe and effective anti-viral treatments
are available for the control of HBV and HCV have been shown to reduce the risk of
developing liver cancer.6,10
HCV treatment is also safe and effective among people who inject drugs,11,12 and guidelines
encourage treatment in this group.13-15 Nevertheless, due to the extended treatment
regimens and adverse side-effects, rates of antiviral therapy among this group remain
low.16,17 Fortunately, safe, well-tolerated and highly effective therapies for HCV infection
have become available.18,19
Human papilloma virus
Human papilloma virus (HPV) is transmitted through skin-to-skin or skin-to-mucosa contact.6
HPV is a virus that comprises many types, some of which (the so-called “high risk” types)
can lead to cervical cancer. Most people will have HPV at some time in their life but not
know. Both men and women are commonly infected with HPV, and inadvertently transmit it
to others. The body's immune system usually clears the virus in around 12 months.4
4
Although HPV infection is very common, most women with HPV will not develop cervical
cancer. However, when high risk HPV infections (especially types 16 and 18) take longer
than usual to clear from the body, they increase the risk of cervical cancer. When cervical
cancer occurs, HPV is found in almost all cases. Additionally, HPV types 16 and 18 have
been found to cause up to 50 percent of vaginal, vulvar, and penile cancers.6,20
HPV is also associated with anal and other genital cancers.20 Approximately 85% of anal
cancer cases are caused by HPV type 16.20 More recently, researchers have estimated that
HPV type 16 is associated with more than 50% of cases of oropharynx cancer (cancer of the
middle part of the throat including the soft palate, the base of the tongue, and the tonsils).20
The incidence of HPV-associated oropharyngeal cancer has increased over the past 20
years, especially among men; and it is estimated that by the end of the next decade, HPV
will cause more oropharyngeal cancers than cervical cancers.21 Some studies have found
that skin cancers in people with weakened immune systems contain HPV, however ongoing
research is needed to determine the role of HPV in skin cancers.6
The HPV vaccine can prevent more than 70% of infections associated with the development
of cervical abnormalities that can progress to cancer.22 Gardasil is the HPV vaccine used in
Australia, whereas Cervaix is another competing HPV vaccine used in the UK. Australia’s
National Human Papillomavirus vaccination program began in 2007 to protect young women
against HPV infections that can lead to cancer. From 2013, the current school based
program for young women aged 12-13 years was extended to males aged 12-13 years, with
a catch up program in 2013 and 2014 for males aged 14-15 years.23
Human immunodeficiency virus
People who have unprotected sex with multiple partners, people who inject drugs and share
injecting equipment, and infants of mothers living with human immunodeficiency virus (HIV)
are at increased risk of acquiring HIV. At the early stages of discovery of HIV some people
acquired HIV via blood transfusions, before appropriate tests of the blood supply became
available. All blood products in Australia are extensively tested for HIV, so the likelihood of
acquiring HIV from a blood transfusion in Australia is extremely low. People with HIV and
acquired immunodeficiency syndrome (AIDS) have weakened immune systems and are at
risk of developing a number of cancers, including Kaposi sarcoma, non-Hodgkin lymphoma,
anal cancer, Hodgkin lymphoma, and cervical cancer.6
Human T-cell lymphotropic virus 1
Human T-cell lymphotropic virus 1 (HTLV-1) is transmitted via breast feeding, sexual
contact, blood transfusions, and the sharing of injecting equipment among people who inject
drugs. Regions that have high rates of HTLV-1 include south western Japan, parts of subSaharan Africa, the Caribbean Islands, and South America. Infection has also been
detected among Australia’s Aboriginal peoples. Found in at least 90 percent of cases of
adult T-cell leukemia/lymphomas, HTLV-1 is a diagnostic criterion for this cancer.6
Kaposi Sarcoma Associated Herpesvirus
Kaposi Sarcoma Associated Herpesvirus (KSHV), also known as Human Herpesvirus 8
(HHV8) is a common infection, primarily transmitted via saliva. KSHV/HHV8 has been linked
to Kaposi Sarcoma, a rare type of cancer in western countries.6 Only some groups of people
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who are immune suppressed (HIV patients, organ transplant patients) are at higher risk of
developing Kaposi Sarcoma. KSHV has also been associated with Primary Effusion
Lymphoma, a type of blood cancer which is a rare complication occurring mainly among
people with HIV.6
Helicobacter pylori
Helicobacter pylori (H. pylori) is a bacterium which was discovered as causing ulcers in the
stomach and duodenum (the first section of the small intestine), in Australia in 1982. In 1994,
the International Agency for Research on Cancer (IARC) classified chronic infection with H.
pylori as carcinogenic (cancer causing) to humans. A review of the evidence conducted by
IARC in 2012 concluded that chronic infection with H. pylori causes stomach cancer and a
rare type of lymphoma, low-grade B-cell MALT gastric lymphoma. As with many other
infections associated with cancers, H. pylori is a common infection in the human population.
Symptoms can range from none to serious upper gastric discomfort and ulcers. Cancer only
occurs in a small proportion of those people with the bacteria.6
Opisthorchis viverrine and Clonorchis sinensis (liver flukes)
A person may become infected by the liver fluke after ingesting raw or undercooked fish.
Liver fluke infection occurs frequently in countries whose residents traditionally eat
raw/undercooked fish, including Thailand, China, Republic of Korea, Laos and Cambodia.
Chronic infection with liver flukes can cause cholangiocarcinoma, a type of liver cancer.
Cholangiocarcinoma is a common cancer in those countries that have high rates of chronic
liver fluke infection, especially Thailand and the Republic of Korea.6
Schistosoma haematobium
Schistosomes are parasitic blood dwelling flatworms found mainly in sub-Saharan Africa.
Schistosoma infections occur after direct contact with fresh water that contain newly hatched
Schistosoma worms. Chronic infection with Schistosoma haematobium (S. haematobium)
can cause bladder cancer. S. haematobium eggs have been found in bladder tumours in
85% of bladder cancer patients in South Africa.6
The following websites are recommended for further information and support:
National Cancer Institute
Cancer Research UK
International Agency for Research on Cancer
Cancer Council Helpline on (freecall) 13 11 20
Publication Date: June 2013
Validation
This factsheet has been reviewed by:
6
Professor Freddy Sitas
Director, Cancer Research Division
Cancer Council NSW
Dr Monica Robotin
Medical Director, Cancer Information and Support Services
Cancer Council NSW
Kathy Chapman
Director, Health Strategies Division
Cancer Council NSW
Dr Libby Topp
Manager, Research Strategy Unit
Cancer Council NSW
For further information contact:
Nicci Bartley
Research Strategy Unit Project Officer
Cancer Council NSW
[email protected]
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References
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Oncology. 2012;13(6):607-15.
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Agents. Lyon: International Agency for Research on Cancer.
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http://www.hepatitisaustralia.com/about-hepatitis/hepatitis-b
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Medicine. 2013;366:273-5.
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Australia. 2012;196(10):629-32.
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http://www.cancer.gov/cancertopics/factsheet/Risk/HPV
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