Global burden of cancers attributable to infections in 2008: a review and synthetic analysis

doi:10.1016/S1470-2045(12)70137-7

The Lancet Oncology

Volume 13, Issue 6, June 2012, Pages 607-615

https://doi.org/10.1016/S1470-2045(12)70137-7 Get rights and content

Summary

Background

Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted.

Methods

We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data.

Findings

Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years.

Interpretation

Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide.

Funding

Fondation Innovations en Infectiologie (FINOVI) and the Bill & Melinda Gates Foundation (BMGF).

Introduction

Infection is recognised as a major cause of cancer worldwide. Prevention and treatment of infectious agents have already had a substantial effect on cancer prevention.¹ A useful statistic to quantify this effect is the population attributable fraction (PAF), defined as the proportion of new cancer cases in a specific population that would have been prevented by a hypothetical intervention on a specific exposure. For infectious agents classified as carcinogenic to humans,² we calculated the PAF worldwide and in eight regions, using GLOBOCAN statistics on estimated cancer incidence in 2008.³ Similar calculations have been done for cancer incidence data from 1990⁴ and 2002.⁵ In this report, we substantially revised the methods to reduce uncertainties and biases resulting from lack of data on population-specific and age-specific infection prevalence. We also discuss a framework for calculating global attributable fractions that might be applied to other causes of cancer. Some physical or chemical carcinogens act synergistically with infectious agents to cause cancers; in these cases, the attributable fractions can add to more than 100%. We report the attributable fractions of infectious agents but do not report the contribution of any non-infectious cofactor.

Section snippets

Infectious agents

In February, 2009, an expert working group reviewed infectious agents that have been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) Monographs programme.⁶ Panel 1 shows these agents and their associated cancers, namely Helicobacter pylori (H pylori), hepatitis B virus (HBV), hepatitis C virus (HCV), Opisthorchis viverrini, Clonorchis sinensis, human papillomavirus (HPV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus type 1 (HTLV-1),

Results

Table 2 shows the estimated number of cancer cases attributed to infection in 2008, in less developed and more developed regions. Of the estimated 12·7 million new cancers worldwide, around 2 million were attributable to infections, of which 1·6 million (80%) occurred in less developed regions. HBV, HCV, HPV, and H pylori were together responsible for 1·9 million cases worldwide. Figure 2 shows the contribution of these infectious agents to cancer burden in less developed and more developed

Discussion

The analysis described in this report and in the appendix shows that infection is an important contributor to the global cancer burden, with 16·1% of cancers diagnosed in 2008 being attributable to infections, although the contribution due to infection varies widely from region to region. The estimated burden of cancer in 2008 attributable to infections is an update of previous estimates for 2002⁵ and 1990.⁴ Our estimates for 2008 are slightly lower than those for 2002, for global burden of

References (26)

V Bouvard et al.
A review of human carcinogens–Part B: biological agents
Lancet Oncol
(2009)
A Shin et al.
Population attributable fraction of infection-related cancers in Korea
Ann Oncol
(2011)
AM Ekstrom et al.
Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection
Gastroenterology
(2001)
V Herrera et al.
Helicobacter pylori and gastric adenocarcinoma
Clin Microbiol Infect
(2009)
MH Chang et al.
Decreased incidence of hepatocellular carcinoma in hepatitis B vaccines: a 20-year follow-up study
J Natl Cancer Inst
(2009)
Monographs on the evaluation of carcinogenic risks to humans, volume 100. A review of carcinogen—Part B: biological agents
(2011)
J Ferlay et al.
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008
Int J Cancer
(2010)
P Pisani et al.
Cancer and infection: estimates of the attributable fraction in 1990
Cancer Epidemiol Biomarkers Prev
(1997)
DM Parkin
The global health burden of infection-associated cancers in the year 2002
Int J Cancer
(2006)
World population prospects: the 2008 revision highlights
(2009)

J Ferlay et al.

GLOBOCAN 2008 v1.2, cancer incidence and mortality worldwide: IARC CancerBase 10

(2010)

DM Parkin et al.

Cancer incidence in five continents, vol VIII. IARC scientific publications 155

(2002)

MP Curado et al.

Cancer incidence in five continents, vol IX. IARC scientific publications 160

(2007)

Cited by (1948)

A dual-electrode label-free immunosensor based on in situ prepared Au–MoO<inf>3</inf>-Chi/porous graphene nanoparticles for point-of-care detection of cholangiocarcinoma
2024, Talanta
A novel label-free electrochemical immunosensor was prepared for the detection of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) as biomarkers of cholangiocarcinoma (CCA). A nanocomposite of gold nanoparticles, molybdenum trioxide, and chitosan (Au–MoO₃-Chi) was layer-by-layer assembled on the porous graphene (PG) modified a dual screen-printed electrode using a self-assembling technique, which increased surface area and conductivity and enhanced the adsorption of immobilized antibodies. The stepwise self-assembling procedure of the modified electrode was further characterized morphologically and functionally. The electroanalytical detection of biomarkers was based on the interaction between the antibody and antigen of each marker via linear sweep voltammetry using ferrocyanide/ferricyanide as an electrochemical redox indicator. Under optimized conditions, the fabricated immunosensor showed linear relationships between current change (ΔI) and antigen concentrations in two ranges: 0.0025–0.1 U mL⁻¹ and 0.1–1.0 U mL⁻¹ for CA19-9, and 0.001–0.01 ng mL⁻¹ and 0.01–1.0 ng mL⁻¹ for CEA. The limits of detection (LOD) were 1.0 mU mL⁻¹ for CA19-9 and 0.5 pg mL⁻¹ for CEA. Limits of quantitation (LOQ) were 3.3 mU mL⁻¹ for CA19-9 and 1.6 pg mL⁻¹ for CEA. The selectivity of the developed immunosensor was tested on mixtures of antigens and was then successfully applied to determine CA19-9 and CEA in human serum samples, producing satisfactory results consistent with the clinical method.
Gut microbial dysbiosis in the pathogenesis of leukemia: an immune-based perspective
2024, Experimental Hematology
Leukemias are a set of clonal hematopoietic malignant diseases that develop in the bone marrow. Several factors influence leukemia development and progression. Among these, the gut microbiota is a major factor influencing a wide array of its processes. The gut microbial composition is linked to the risk of tumor development and the host's ability to respond to treatment, mostly due to the immune-modulatory effects of their metabolites. Despite such strong evidence, its role in the development of hematologic malignancies still requires attention of investigators worldwide. In this review, we make an effort to discuss the role of host gut microbiota–immune crosstalk in leukemia development and progression. Additionally, we highlight certain recently developed strategies to modify the gut microbial composition that may help to overcome dysbiosis in leukemia patients in the near future.
Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy
2024, Pharmacological Research
Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.
Cancer burden attributable to risk factors, 1990–2019: A comparative risk assessment
2024, iScience
An up-to-date comprehensive assessment of the cancer burden attributable to risk factors is essential for cancer prevention. We analyzed the population attributable fraction (PAF) of cancer disability-adjusted life years (DALYs) attributable to 11 level 2 risk factors using data from the Global Burden and Disease Study (GBD) 2019. We highlighted that almost half of the cancer DALYs can be preventable by modifying relevant risk factors. The attributable cancer DALYs increased by 60.42%–105.0 million from 1990 to 2019. Tobacco, dietary risks, alcohol use, high body-mass index, and air pollution were the top five risk factors. The PAFs attributable to high fasting plasma glucose, high body-mass index, and low physical activity have increased worldwide from 1990 to 2019. Unsafe sex was the leading risk factor for women before age of 54. Tailored prevention programs targeted at specific populations should be scaled up to reduce the cancer burden in the future.
Trends of gastric cancer burdens attributable to risk factors in China from 2000 to 2050
2024, The Lancet Regional Health - Western Pacific
The incidence of gastric cancer (GC) decreased in past decades, which was thought largely attributable to risk factors control, yet China still accounts for 44% of global GC burdens. We aimed to estimate changing trajectories of proportions of GC burdens attributable to modifiable risk factors from 2000 to 2050 in China, to inform future targeted preventive strategies.
The incidence and new cases of GC were predicted to 2050 using Bayesian age-period-cohort model based on incidence data by anatomical subsites drawn from 682 cancer registries from National Central Cancer Registry. Population attributable fractions (PAFs) were calculated based on prevalence of risk factors and relative risks with GC. Temporal trends of PAFs were described by sex and categories of risk factors using joinpoint analysis.
We observed declining trends of PAFs of Helicobacter pylori (H. pylori) infection, smoking, pickled vegetable and alcohol consumption, but increasing trends of PAFs of unhealthy body mass index and diabetes for GC in China. The combined PAFs of these risk factors were estimated to decrease by 10.57% from 2000 to 2050 for GC. We estimated there will be 279,707 GC (122,796 cardia gastric cancer [CGC] and 156,911 non-cardia gastric cancer [NCGC]) cases in 2050. Out of these cases, 70.18% of GC cases could be attributable to modifiable risk factors, while H. pylori infection was predicted to be responsible for 40.7% of CGC and 62.1% of NCGC cases in 2050.
More than half of GC remained attributable to modifiable risk factors in China. Continued effective strategies on risk factors control are needed to reduce the burden of this highly life-threatening cancer in future.
Beijing Nova Program (No. Z201100006820069), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-023), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-010), Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star).
Evolving Concepts in Helicobacter pylori Management
2024, Gastroenterology
Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.

View all citing articles on Scopus

View full text

ArticlesGlobal burden of cancers attributable to infections in 2008: a review and synthetic analysis

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Infectious agents

Results

Discussion

Lancet Oncol

Ann Oncol

Gastroenterology

Clin Microbiol Infect

Decreased incidence of hepatocellular carcinoma in hepatitis B vaccines: a 20-year follow-up study

J Natl Cancer Inst

Monographs on the evaluation of carcinogenic risks to humans, volume 100. A review of carcinogen—Part B: biological agents

Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008

Int J Cancer

Cancer and infection: estimates of the attributable fraction in 1990

Cancer Epidemiol Biomarkers Prev

The global health burden of infection-associated cancers in the year 2002

Int J Cancer

World population prospects: the 2008 revision highlights

GLOBOCAN 2008 v1.2, cancer incidence and mortality worldwide: IARC CancerBase 10

Cancer incidence in five continents, vol VIII. IARC scientific publications 155

Cancer incidence in five continents, vol IX. IARC scientific publications 160

Articles
Global burden of cancers attributable to infections in 2008: a review and synthetic analysis