Opinion

VIEWPOINT

Rolando Herrero, MD,

PhD
Section of Early
Detection and
Prevention,
International Agency
for Research on Cancer,
Lyon, France.
Julie Parsonnet, MD
Department of
Medicine, Stanford
University Medical
Center, Stanford,
California.
Edwin Robert
Greenberg, MD
Division of Public
Health Sciences, Fred
Hutchinson Cancer
Research Center,
Seattle, Washington.

Corresponding
Author: Rolando
Herrero, MD, PhD,
Section of Early
Detection and
Prevention,
International Agency
for Research on Cancer,
150 Cours Albert
Thomas, 69372 Lyon,
France (herreror@iarc
.fr).

Prevention of Gastric Cancer

This year, it is estimated that more than 700 000
people will die of gastric cancer, making this disease the
third most common cause of cancer death globally.1 Although gastric cancer rates have been declining by approximately 2% per year, the numbers of cases and
deaths are expected to increase in coming years, reflecting increasing numbers of older (and thus, higher-risk)
individuals in the world. Despite its importance, gastric
cancer receives little attention from research funding
agencies or public health organizations. For example, the
National Cancer Institute annually spends approximately $12 million on programs directly related to gastric cancer, just 0.2% of its budget, and only 10% of this
amount is allocated for prevention research.2 In contrast, the annual cost of treating gastric cancer in the
United States, a lower-risk country, is estimated at approximately $2 billion.3
Of the 989 000 gastric cancer cases in the world
in 2008, an estimated 770 000 could be attributed to
chronic infection with Helicobacter pylori.4 Although
there have been calls to prevent gastric cancer by
screening for this infection and treating individuals
who test positive, no randomized trial had shown a
clear benefit of this approach until recently. In 2012, a
trial in a general population of adults in China reported
a statistically significant reduction in gastric cancer risk
following treatment (4.6% in the control group vs
3.0% in the treated group; odds ratio, 0.61 [95% CI,
0.38-0.96]),5 and a meta-analysis of 6 reported randomized trials among asymptomatic adults has estimated a similar benefit (2.4% in the control group vs
1.6% in the treated group; relative risk, 0.66 [95% CI,
0.46-0.95]).6 Reduced risk of subsequent gastric cancer was also seen in 2 randomized trials of H pylori
treatment after endoscopic mucosal resection of early
gastric cancer.6
Although these data support screening for and treating H pylori infection, important uncertainties remain.
The trials, even viewed in aggregate, do not permit precise estimation of the benefits or possible harms of the
interventions, and the relative lack of success of antibiotic regimens used in some trials likely attenuated observed effects. Trial participants were principally middleaged Asian adults, so the generalizability of results to
other populations is uncertain and no trial provided direct data on the performance of programs applied in
community settings.
Population-based H pylori treatment has been
shown to reduce clinical visits for dyspepsia symptoms7
and may also prevent peptic ulcers. Possible harms include increased risk of esophageal adenocarcinoma. Reported protective associations between H pylori infection and asthma, other allergic diseases, obesity, diarrheal
diseases, and activation of latent tuberculosis are of uncertain significance and may not reflect a causal role.

Population-based H pylori treatment could select for antibiotic-resistant pathogens in the community, although in many countries, such an effect might be overshadowed by indiscriminate use of antibiotics for other
human and veterinary purposes. Treating H pylori will alter the overall composition of the intestinal flora; the
health consequences are unknown.
Screening and treatment for H pylori is generally acceptable and affordable. An inexpensive serological test
can determine who may be infected, with a sensitivity
and specificity that could be sufficient for populationbased prevention programs. Low-cost treatment regimens using 2 or 3 generic antibiotics plus a proton pump
inhibitor for 7 to 14 days can eradicate the infection in
more than 80% of cases, depending on the antibiotic resistance patterns of H pylori within the population.8 Economic modeling studies indicate that H pylori screening and treatment strategies are cost-effective under a
large range of assumptions about effectiveness and
costs.9 However, the models are limited by reliance on
observational data rather than randomized trial results, by a lack of information on possible adverse effects of treatment, and by limited data from lowerincome countries.
In December 2013, a working group meeting convened by the International Agency for Research on
Cancer reviewed evidence regarding eradication of
H pylori as a strategy for gastric cancer prevention and
prepared a technical report.10 The participants in the
working group concluded that the large global burden
of gastric cancer and the feasibility of treating its principal cause make this disease a logical target for intervention. They further called for countries with high
rates of gastric cancer to focus more resources on this
condition, to include it within their national cancer
control programs, and to assess its human and economic effects and the potential value of prevention
strategies.
Within the next 10 years, results from several
ongoing randomized trials will likely resolve many
uncertainties about H pylori screening and treatment.
Nevertheless, practical questions about the implementation and outcomes of population-based gastric
cancer prevention programs could best be answered
by direct observation in the communities where they
are applied. National health authorities should consider conducting demonstration programs of H pylori
screening and eradication using designs that can provide an unbiased assessment of program effectiveness. The determination of whether and how to
undertake such programs will require population data
about gastric cancer rates and H pylori infection
prevalence, information that also may identify subpopulations at particularly elevated risk (eg, immigrants from high-risk countries). From a practical

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Opinion Viewpoint

standpoint, many countries will first need to develop more effective systems for determining and tabulating causes of death and
for cancer registration. Locally derived data on antibiotic resistance in H pylori, treatment regimen effectiveness, and reinfection rates will also be useful for planning.
The particular features of an intervention, such as the target age,
screening approach, and treatment regimen, can be adapted based
on the results of cost-effectiveness models, available resources, and
prevailing medical and public health practices. Any programs that
ARTICLE INFORMATION
Conflict of Interest Disclosures: All authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
REFERENCES
1. International Agency for Research on Cancer.
Stomach cancer. Estimated incidence, mortality and
prevalence worldwide in 2012. http://globocan.iarc
.fr/old/FactSheets/cancers/stomach-new.asp.
Accessed April 25, 2014.
2. National Cancer Institute at the National
Institutes of Health. A snapshot of stomach cancer.
http://www.cancer.gov/researchandfunding
/snapshots/stomach. Accessed July 22, 2014.
3. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ,
Brown ML. Projections of the cost of cancer care in

1198

are implemented should include objective assessments of feasibility, acceptance, costs, effectiveness, and adverse consequences;
these results must be made available in the public domain. A clusterrandomized trial design with staged implementation is a possible assessment strategy.
Ignoring gastric cancer in the hope that it will soon disappear is
not a tenable health policy. Implementing large, population-based
evaluationprogramsofHpyloriscreeningandtreatmentoffersapromising opportunity to prevent deaths from this important cancer.

the United States: 2010-2020. J Natl Cancer Inst.

2011;103(2):117-128.
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de Martel C. Global burden of gastric cancer
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Helicobacter pylori eradication on dyspepsia, health

resource use, and quality of life in the Bristol

helicobacter project: randomised controlled trial.
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8. Gatta L, Vakil N, Vaira D, Scarpignato C. Global
eradication rates for Helicobacter pylori infection:
systematic review and meta-analysis of sequential
therapy. BMJ. 2013;347:f4587.
9. Lansdorp-Vogelaar I, Sharp L. Cost-effectiveness
of screening and treating Helicobacter pylori for
gastric cancer prevention. Best Pract Res Clin
Gastroenterol. 2013;27(6):933-947.
10. International Agency for Research on Cancer.
IARC Working Group Reports. Helicobacter pylori:
eradication as a strategy for preventing gastric
cancer. http://www.iarc.fr/en/publications
/pdfs-online/wrk/wrk8/. Accessed August 28, 2014.

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