H. pylori and cancer

Using GLOBOCAN cancer incidence for 2024, IARC researchers estimated that 2.3 million new cancers, 12% of the global total, were attributable to infections. H. pylori accounted for the largest number (760,000, a population-attributable fraction of 4%), ahead of human papillomavirus (750,000), hepatitis B (360,000), Epstein-Barr virus (260,000) and hepatitis C (160,000). Eastern Asia carried 42% of all infection-attributable cancers [1]. An earlier IARC update that used the more sensitive immunoblot blood test put the share of non-cardia stomach cancers attributable to H. pylori at 89.0%, up from 74.7% with the older ELISA test [6]. Looking forward, an IARC projection for people born between 2008 and 2017 expects 15.6 million lifetime stomach cancers in that generation, 76% of them attributable to H. pylori, with two-thirds in Asia [14].

A meta-analysis of 184 studies from 62 countries estimated that about 4.4 billion people carried H. pylori in 2015. Prevalence was highest in Africa (70.1%) and lowest in Oceania (24.4%), and ranged by country from 18.9% in Switzerland to 87.7% in Nigeria [7]. A larger update of 1,748 studies from 111 countries found adult prevalence fell from 52.6% before 1990 to 43.9% in 2015 to 2022, a decline of 15.9% over three decades, while prevalence in children and adolescents stayed at 35.1% and fell in no WHO region. Stomach cancer incidence fell in the countries where infection declined [8].

In a pooled analysis of 12 case-control studies nested in prospective cohorts (1,228 cases), infection was associated with 3.0 times the odds of non-cardia stomach cancer (95% CI 2.3 to 3.8), and 5.9 times (3.4 to 10.3) when blood had been taken 10 or more years before diagnosis; the authors judged 5.9 the best estimate, because infection can clear as cancer develops. There was no association with cardia cancer (odds ratio 1.0) [13]. The absolute numbers are smaller than the relative risk suggests. In 1,526 Japanese patients followed with endoscopy for a mean 7.8 years, stomach cancer developed in 36 of 1,246 infected patients (2.9%) and in none of 280 uninfected patients. Risk concentrated in those with severe atrophy, corpus-predominant gastritis or intestinal metaplasia, and none of the 275 patients with duodenal ulcers developed stomach cancer [9]. Set against roughly 4.4 billion carriers [7], about 760,000 attributable cancers a year [1] means the great majority of infected people never develop the disease.

Strains differ. CagA (cytotoxin-associated gene A) is a protein made by some H. pylori strains. A meta-analysis of 16 case-control studies (2,284 cases, 2,770 controls) found that H. pylori antibodies raised the odds of stomach cancer 2.28-fold and CagA antibodies 2.87-fold. Among infected people, CagA-positive strains added further risk: 1.64 times overall (95% CI 1.21 to 2.24) and 2.01 times for non-cardia cancer (1.21 to 3.32). Cardia cancer was not associated with either infection or CagA status [10].

A Cochrane review of 101 diagnostic-accuracy studies (11,003 participants) compared non-invasive tests against endoscopic biopsy, the confirming test. At a fixed specificity of 0.90, sensitivity was 0.94 for the carbon-13 urea breath test, 0.92 for the carbon-14 breath test, 0.84 for blood antibody tests (serology) and 0.83 for stool antigen tests. Per 1,000 people tested at a typical 53.7% prevalence, that is about 30 missed infections with the carbon-13 breath test against 86 with serology and 89 with stool antigen. The authors concluded breath tests had high accuracy and the others less, in people who had not recently taken antibiotics or acid-suppressing proton pump inhibitors; much of the comparison was indirect [11].

Treatment is a course of antibiotics with acid suppression. The American College of Gastroenterology 2024 guideline prefers 14 days of bismuth quadruple therapy for people treated for the first time when antibiotic susceptibility is unknown, with rifabutin triple therapy or potassium-competitive acid blocker dual therapy for 14 days as alternatives for people without penicillin allergy. Regimens containing clarithromycin or levofloxacin are reserved for infections with confirmed susceptibility, and every treatment is followed by a test of cure [12]. The European Maastricht VI/Florence consensus, written by 41 experts from 29 countries, describes rising antibiotic resistance as the main challenge to treatment and supports susceptibility testing [15].

A 2025 meta-analysis of 11 randomised trials and 13 observational studies found eradication therapy lowered stomach cancer in healthy H. pylori-positive adults (8 trials, relative risk 0.64, 95% CI 0.48 to 0.84) and stomach cancer death (5 trials, 0.78, 0.62 to 0.98). After endoscopic removal of early cancer, it lowered new cancers (3 trials, 0.52), and observational studies agreed (0.56 in people without neoplasia) [5]. In a Korean trial of 1,838 first-degree relatives of stomach cancer patients, cancer developed in 1.2% of the treated group and 2.7% of the placebo group over a median 9.2 years (hazard ratio 0.45); among those whose infection was actually cleared it was 0.8% against 2.9% with persistent infection (0.27). Mild side effects were more common with treatment (53.0% against 19.1%) [2]. In 396 patients after removal of early stomach cancer, new cancer developed in 7.2% treated and 13.4% on placebo over 5.9 years (hazard ratio 0.50), and the thinning of the stomach lining improved in 48.4% against 15.0% [4]. In the Shandong Intervention Trial in Linqu County, China, which randomised 2,258 seropositive adults, two weeks of treatment lowered stomach cancer incidence over 22 years (odds ratio 0.48) and stomach cancer death (hazard ratio 0.62) [3].

H. pylori is the largest single factor, but not the only one. The highest salt intake was associated with 68% more stomach cancer than the lowest across 10 cohorts and 268,718 people (relative risk 1.68) [16]. Current smokers had 53% more stomach cancer than never smokers across 92 studies, and 2.08 times for cardia cancer [17]. The highest processed-meat intake was associated with 45% more [18], and a parent, sibling or child with stomach cancer with 84% higher odds (odds ratio 1.84) [19]. The Korean family-history trial describes infection and a family history as the two main risk factors for stomach cancer [2].