Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

Department of Medicine and Department of Gastrointestinal Oncology 1st Faculty of Medicine Charles University and Military University Hospital Prague Czech Republic

Freiburg Klinik für Innere Medizin 2 Universitätsklinikum Freiburg Freiburg Germany

Health Bureau of Linqu County Weifang China

Institute of Pathology Friedrich Alexander University Erlangen Nuremberg Klinikum Bayreuth Bayreuth Germany

Key Laboratory of Carcinogenesis and Translational Research Department of Cancer Epidemiology Peking University Cancer Hospital and Institute Beijing China

School of Medicine and Health Technical University of Munich Munich Germany

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Department of Cancer Epidemiology Peking University Cancer Hospital and Institute Beijing China

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Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). PubMed

Chen, Y. C. et al. Global prevalence of Helicobacter pylori infection and incidence of gastric cancer between 1980 and 2022. Gastroenterology 166, 605–619 (2024). PubMed

You, W. C. et al. Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors. J. Natl Cancer Inst. 92, 1607–1612 (2000). PubMed

Correa, P. Human gastric carcinogenesis: a multistep and multifactorial process—First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 52, 6735–6740 (1992).

Correa, P. et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy. J. Natl Cancer Inst. 92, 1881–1888 (2000). PubMed

Piazuelo, M. B. et al. The Colombian Chemoprevention Trial: 20-year follow-up of a cohort of patients with gastric precancerous lesions. Gastroenterology 160, 1106–1117 (2021). PubMed

Saito, D. et al. Impact of H. pylori eradication on gastric cancer prevention: endoscopic results of the Japanese intervention trial (JITHP-study). A randomized multi-center trial. Gastroenterology 128, A4 (2005).

Choi, I. J. et al. Family history of gastric cancer and Helicobacter pylori treatment. N. Engl. J. Med. 382, 427–436 (2020). PubMed

Wong, B. C. et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 291, 187–194 (2004). PubMed

Yan, L. et al. Effect of Helicobacter pylori eradication on gastric cancer prevention: updated report from a randomized controlled trial with 26.5 years of follow-up. Gastroenterology 163, 154–162 (2022). PubMed

Leung, W. K. et al. Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication. Gut 53, 1244–1249 (2004). PubMed PMC

Zhou, L. et al. Relationship of Helicobacter pylori eradication with gastric cancer and gastric mucosal histological changes: a 10-year follow-up study. Chin. Med. J. (Engl.) 127, 1454–1458 (2014). PubMed

You, W. C. et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J. Natl Cancer Inst. 98, 974–983 (2006). PubMed

Ma, J. L. et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J. Natl Cancer Inst. 104, 488–492 (2012). PubMed PMC

Li, W. Q. et al. Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. Br. Med. J. 366, l5016 (2019).

Li, W. Q. et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. J. Natl Cancer Inst. 106, dju116 (2014). PubMed PMC

Wong, B. C. et al. Effects of selective COX-2 inhibitor and Helicobacter pylori eradication on precancerous gastric lesions. Gut 61, 812–818 (2012). PubMed

You, W. C. et al. Precancerous gastric lesions in a population at high risk of stomach cancer. Cancer Res. 53, 1317–1321 (1993). PubMed

Ford, A. C., Yuan, Y. & Moayyedi, P. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Gut 69, 2113–2121 (2020). PubMed

Ford, A. C., Yuan, Y. & Moayyedi, P. Long-term impact of Helicobacter pylori eradication therapy on gastric cancer incidence and mortality in healthy infected individuals: a meta-analysis beyond 10 years of follow-up. Gastroenterology 163, 754–756 (2022). PubMed

Helicobacter pylori Working Group. Helicobacter pylori eradication as a strategy for preventing gastric cancer. IARC Working Group Report Vol. 8 (IARC, 2014); https://publications.iarc.fr/Book-And-Report-Series/Iarc-Working-Group-Reports/-Em-Helicobacter-Pylori-Em-Eradication-As-A-Strategy-For-Preventing-Gastric-Cancer-2014

Gao, H. et al. Systematic review with meta-analysis: association of helicobacter pylori infection with esophageal cancer. Gastroenterol. Res. Pract. 2019, 1953497 (2019). PubMed PMC

El-Serag, H. B. et al. Houston Consensus Conference on Testing for Helicobacter pylori infection in the United States. Clin. Gastroenterol. Hepatol. 16, 992–1002 (2018). PubMed PMC

Malfertheiner, P. et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 71, 1724–1762 (2022).

Sugano, K. et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 64, 1353–1367 (2015). PubMed

Gupta, S. et al. AGA clinical practice guidelines on management of gastric intestinal metaplasia. Gastroenterology 158, 693–702 (2020). PubMed

Pan, K. F. et al. A large randomised controlled intervention trial to prevent gastric cancer by eradication of Helicobacter pylori in Linqu County, China: baseline results and factors affecting the eradication. Gut 65, 9–18 (2016). PubMed

Zhou, L. et al. 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment. Chin. Med. J. (Engl.) 135, 2899–2910 (2022). PubMed

Song, Z. et al. Prospective multi-region study on primary antibiotic resistance of Helicobacter pylori strains isolated from Chinese patients. Dig. Liver Dis. 46, 1077–1081 (2014). PubMed

Chen, J. et al. Primary antibiotic resistance of Helicobacter pylori in different regions of China: a systematic review and meta-analysis. Pathogens 11, 786 (2022). PubMed PMC

De Francesco, V. et al. Worldwide H. pylori antibiotic resistance: a systematic review. J. Gastrointestin. Liver Dis. 19, 409–414 (2010). PubMed

Camargo, M. C. et al. The problem of Helicobacter pylori resistance to antibiotics: a systematic review in Latin America. Am. J. Gastroenterol. 109, 485–495 (2014). PubMed PMC

Kuo, Y. T. et al. Primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 2, 707–715 (2017). PubMed

Savoldi, A., Carrara, E., Graham, D. Y., Conti, M. & Tacconelli, E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology 155, 1372–1382 (2018). PubMed

Chey, W. D., Leontiadis, G. I., Howden, C. W. & Moss, S. F. ACG clinical guideline: treatment of Helicobacter pylori infection. Am. J. Gastroenterol. 112, 212–239 (2017). PubMed

Fallone, C. A., Moss, S. F. & Malfertheiner, P. Reconciliation of recent Helicobacter pylori treatment guidelines in a time of increasing resistance to antibiotics. Gastroenterology 157, 44–53 (2019). PubMed

Gerrits, M. M., van Vliet, A. H., Kuipers, E. J. & Kusters, J. G. Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications. Lancet Infect. Dis. 6, 699–709 (2006). PubMed

Kumar, S., Metz, D. C., Kaplan, D. E. & Goldberg, D. S. Low rates of retesting for eradication of Helicobacter pylori infection after treatment in the Veterans Health Administration. Clin. Gastroenterol. Hepatol. 19, 305–313 (2021). PubMed

Graham, D. Y. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology 148, 719–731 (2015). PubMed

Yang, L. et al. The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study. Lancet Public Health 6, e888–e896 (2021). PubMed PMC

Doorakkers, E., Lagergren, J., Santoni, G., Engstrand, L. & Brusselaers, N. Helicobacter pylori eradication treatment and the risk of Barrett’s esophagus and esophageal adenocarcinoma. Helicobacter 25, e12688 (2020). PubMed

Chiang, T. H. et al. Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands. Gut 70, 243–250 (2021). PubMed

Butt, J. et al. Serologic response to Helicobacter pylori proteins associated with risk of colorectal cancer among diverse populations in the United States. Gastroenterology 156, 175–186 (2019). PubMed

Ralser, A. et al. Helicobacter pylori promotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature. Gut 72, 1258–1270 (2023). PubMed

Wang, T. G., You, W. C., Henderson, B. E. & Blot, W. J. A case-control study of stomach cancer in Shandong Province. Natl Cancer Inst. Monogr. 69, 9–10 (1985). PubMed

You, W. C. et al. Diet and high risk of stomach cancer in Shandong, China. Cancer Res. 48, 3518–3523 (1988). PubMed

Zhang, L. et al. Helicobacter pylori antibodies in relation to precancerous gastric lesions in a high-risk Chinese population. Cancer Epidemiol. Biomark. Prev. 5, 627–630 (1996).

Ma, J. L. et al. Helicobacter pylori infection and mode of transmission in a population at high risk of stomach cancer. Int. J. Epidemiol. 27, 570–573 (1998). PubMed

You, W. C. et al. Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancer. Int. J. Cancer 83, 615–619 (1999). PubMed

Li, W. Q. et al. Beneficial effects of endoscopic screening on gastric cancer and optimal screening interval: a population-based study. Endoscopy 54, 848–858 (2022). PubMed

Grambsch, P. M. & Therneau, T. M. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 81, 515–526 (1994).

Dupont, W. D. Statistical Modeling for Biomedical Researchers: A Simple Introduction to the Analysis of Complex Data (Cambridge Univ. Press, 2009).