Mass Eradication of Helicobacter pylorito Prevent Gastric Cancer: Theoretical and Practical Considerations

Yi-Chia Lee, Tsung-Hsien Chiang, Jyh-Ming Liou, Hsiu-Hsi Chen, Ming-Shiang Wu, David Y Graham, Yi-Chia Lee, Tsung-Hsien Chiang, Jyh-Ming Liou, Hsiu-Hsi Chen, Ming-Shiang Wu, David Y Graham

Abstract

Although the age-adjusted incidence of gastric cancer is declining, the absolute number of new cases of gastric cancer is increasing due to population growth and aging. An effective strategy is needed to prevent this deadly cancer. Among the available strategies, screen-and-treat for Helicobacter pylori infection appears to be the best approach to decrease cancer risk; however, implementation of this strategy on the population level requires a systematic approach. The program also must be integrated into national healthcare priorities to allow the limited resources to be most effectively allocated. Implementation will require adoption of an appropriate screening strategy, an efficient delivery system with a timely referral for a positive test, and standardized treatment regimens based on clinical efficacy, side effects, simplicity, duration, and cost. Within the population, there are subpopulations that vary in risk such that a "one size fits all" approach is unlikely to be ideal. Sensitivity analyses will be required to identify whether the programs can be utilized by heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations.

Keywords: Eradication; Helicobacter pylori; Population screening; Stomach neoplasms.

Figures

Fig. 1
Fig. 1
The preventable phase of a cancer includes (A) the preclinical detectable phase (PCDP; the number in parenthesis indicates the length of the PCDP in years for a specific cancer) and (B) the carcinogenic phase related to exposure to risk factors (well-known risk factors for the development of a specific cancer are shown in parentheses).
Fig. 2
Fig. 2
The efficacy/effectiveness of the population-based interventions for prevention of gastric cancer according to the surrogate end-points of premalignant gastric lesions and primary end-points of gastric cancer incidence and mortality in the Correa’s multistate model. GCA, gastric cancer; s/p, status post.
Fig. 3
Fig. 3
Cost-effectiveness analysis comparing different regimens/strategies using acceptability curves: (A) the choice between sequential and triple therapies in the treatment of H. pylori infection and (B) the choice between screen-and-treat for H. pylori infection and endoscopic screening based on the serum pepsinogen method to prevent death from gastric cancer. Adapted from Liou JM, et al. Lancet 2013;381:205–213, and Lee YC, et al. Cancer Epidemiol Biomarkers Prev 2007;16:875–885.
Fig. 4
Fig. 4
The presence of confounders in the observed relationship between Helicobacter pylori infection and extragastric diseases.

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.
    1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386. doi: 10.1002/ijc.29210.
    1. Herrero R, Parsonnet J, Greenberg ER. Prevention of gastric cancer. JAMA. 2014;312:1197–1198. doi: 10.1001/jama.2014.10498.
    1. Park JY, von Karsa L, Herrero R. Prevention strategies for gastric cancer: a global perspective. Clin Endosc. 2014;47:478–489. doi: 10.5946/ce.2014.47.6.478.
    1. . All nobel prizes in physiology or medicine [Internet] Stockholm: Nobel Media AB; c2015. [cited 2015 Jan 26]. Available from:
    1. Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J Clin Invest. 2007;117:60–69. doi: 10.1172/JCI30111.
    1. IARC Helicobacter pylori Working Group. Helicobacter pylori eradication as a strategy for preventing gastric cancer (IARC Working Group Reports, No. 8) [Internet] Lyon: International Agency for Research on Cancer; 2014. [cited 2015 Nov 9]. Available from: .
    1. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64:1353–1367. doi: 10.1136/gutjnl-2015-309252.
    1. Graham DY, Shiotani A. The time to eradicate gastric cancer is now. Gut. 2005;54:735–738. doi: 10.1136/gut.2004.056549.
    1. Lee YC, Chen TH, Chiu HM, et al. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013;62:676–682. doi: 10.1136/gutjnl-2012-302240.
    1. Lee YC, Chiu HM, Chiang TH, et al. Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions. BMJ Open. 2013;3:e003989. doi: 10.1136/bmjopen-2013-003989.
    1. Wilson JM, Jungner G. Principles and practice of screening for disease. WHO Chron. 1968;22:473.
    1. Taiwan Cancer Registry. Cancer statistics [Internet] Taipei: Taiwan Cancer Registry; c2008. [cited 2015 Jan 5]. Available from: .
    1. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132:1133–1145. doi: 10.1002/ijc.27711.
    1. Wu GH, Auvinen A, Määttänen L, et al. Number of screens for overdetection as an indicator of absolute risk of overdiagnosis in prostate cancer screening. Int J Cancer. 2012;131:1367–1375. doi: 10.1002/ijc.27340.
    1. Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467:1114–1117. doi: 10.1038/nature09515.
    1. Patz EF, Jr, Pinsky P, Gatsonis C, et al. Overdiagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med. 2014;174:269–274. doi: 10.1001/jamainternmed.2013.12738.
    1. Sanduleanu S, Le Clercq CM, Dekker E, et al. Definition and taxonomy of interval colorectal cancers: a proposal for standardising nomenclature. Gut. 2015;64:1257–1267. doi: 10.1136/gutjnl-2014-307992.
    1. Chiang TH, Chuang SL, Chen SL, et al. Difference in performance of fecal immunochemical tests with the same hemoglobin cutoff concentration in a nationwide colorectal cancer screening program. Gastroenterology. 2014;147:1317–1326. doi: 10.1053/j.gastro.2014.08.043.
    1. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356:1928–1943. doi: 10.1056/NEJMoa061760.
    1. Chang MH, Chen CJ, Lai MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. 1997;336:1855–1859. doi: 10.1056/NEJM199706263362602.
    1. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012;13:607–615. doi: 10.1016/S1470-2045(12)70137-7.
    1. Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187–194. doi: 10.1001/jama.291.2.187.
    1. Correa P, Fontham ET, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst. 2000;92:1881–1888. doi: 10.1093/jnci/92.23.1881.
    1. Mera R, Fontham ET, Bravo LE, et al. Long term follow up of patients treated for Helicobacter pylori infection. Gut. 2005;54:1536–1540. doi: 10.1136/gut.2005.072009.
    1. You WC, Brown LM, Zhang L, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006;98:974–983. doi: 10.1093/jnci/djj264.
    1. Li WQ, Ma JL, Zhang L, et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. J Natl Cancer Inst. 2014:106. pii: dju116.
    1. Leung WK, Lin SR, Ching JY, et al. Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication. Gut. 2004;53:1244–1249. doi: 10.1136/gut.2003.034629.
    1. Zhou L. Ten-year follow-up study on the incidence of gastric cancer and the pathological changes of gastric mucosa after H. pylori eradication in China. Gastroenterology. 2008;134(4 Suppl 1):A233. doi: 10.1016/S0016-5085(08)61077-X.
    1. Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392–397. doi: 10.1016/S0140-6736(08)61159-9.
    1. Ford AC, Forman D, Hunt RH, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014;348:g3174. doi: 10.1136/bmj.g3174.
    1. Yoon SB, Park JM, Lim CH, Cho YK, Choi MG. Effect of Helicobacter pylori eradication on metachronous gastric cancer after endoscopic resection of gastric tumors: a meta-analysis. Helicobacter. 2014;19:243–248. doi: 10.1111/hel.12146.
    1. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection: the Maastricht IV/ Florence Consensus Report. Gut. 2012;61:646–664. doi: 10.1136/gutjnl-2012-302084.
    1. Granstrom M, Lehours P, Bengtsson C, Mégraud F. Diagnosis of Helicobacter pylori. Helicobacter. 2008;13(Suppl 1):7–12. doi: 10.1111/j.1523-5378.2008.00637.x.
    1. Gisbert JP, de la Morena F, Abraira V. Accuracy of monoclonal stool antigen test for the diagnosis of H. pylori infection: a systematic review and meta-analysis. Am J Gastroenterol. 2006;101:1921–1930. doi: 10.1111/j.1572-0241.2006.00668.x.
    1. Lee YC, Tseng PH, Liou JM, et al. Performance of a one-step fecal sample-based test for diagnosis of Helicobacter pylori infection in primary care and mass screening settings. J Formos Med Assoc. 2014;113:899–907. doi: 10.1016/j.jfma.2012.05.014.
    1. Loy CT, Irwig LM, Katelaris PH, Talley NJ. Do commercial serological kits for Helicobacter pylori infection differ in accuracy? A meta-analysis. Am J Gastroenterol. 1996;91:1138–1144.
    1. Benson VS, Atkin WS, Green J, et al. Toward standardizing and reporting colorectal cancer screening indicators on an international level: the International Colorectal Cancer Screening Network. Int J Cancer. 2012;130:2961–2973. doi: 10.1002/ijc.26310.
    1. Porras C, Nodora J, Sexton R, et al. Epidemiology of Helicobacter pylori infection in six Latin American countries (SWOG Trial S0701) Cancer Causes Control. 2013;24:209–215. doi: 10.1007/s10552-012-0117-5.
    1. Greenberg ER, Anderson GL, Morgan DR, et al. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet. 2011;378:507–514. doi: 10.1016/S0140-6736(11)60825-8.
    1. Peleteiro B, Bastos A, Ferro A, Lunet N. Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Dig Dis Sci. 2014;59:1698–1709. doi: 10.1007/s10620-014-3063-0.
    1. Lee YC, Wu HM, Chen TH, et al. A community-based study of Helicobacter pylori therapy using the strategy of test, treat, retest, and retreat initial treatment failures. Helicobacter. 2006;11:418–424. doi: 10.1111/j.1523-5378.2006.00432.x.
    1. Graham DY, Dore MP. Variability in the outcome of treatment of Helicobacter pylori infection: a critical analysis. In: Hunt RH, Tytgat GN, editors. Helicobacter pylori: basic mechanisms to clinical cure 1998. Dordrecht: Springer; 1998. pp. 426–440.
    1. Liou JM, Chen CC, Chen MJ, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013;381:205–213. doi: 10.1016/S0140-6736(12)61579-7.
    1. Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014;12:177–186.e3. doi: 10.1016/j.cgh.2013.05.028.
    1. Lee SY. Current progress toward eradicating Helicobacter pylori in East Asian countries: differences in the 2013 revised guidelines between China, Japan, and South Korea. World J Gastroenterol. 2014;20:1493–1502. doi: 10.3748/wjg.v20.i6.1493.
    1. Zullo A, Vaira D, Vakil N, et al. High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther. 2003;17:719–726. doi: 10.1046/j.1365-2036.2003.01461.x.
    1. Romano M, Marmo R, Cuomo A, et al. Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of Helicobacter pylori. Clin Gastroenterol Hepatol. 2003;1:273–278. doi: 10.1016/S1542-3565(03)00131-9.
    1. Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med. 2007;146:556–563. doi: 10.7326/0003-4819-146-8-200704170-00006.
    1. Demir M, Gokturk HS, Ozturk NA, Arslan H, Serin E, Yilmaz U. Clarithromycin resistance and efficacy of clarithromycin-containing triple eradication therapy for Helicobacter pylori infection in type 2 diabetes mellitus patients. South Med J. 2009;102:1116–1120. doi: 10.1097/SMJ.0b013e3181bca538.
    1. Romano M, Cuomo A, Gravina AG, et al. Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial. Gut. 2010;59:1465–1470. doi: 10.1136/gut.2010.215350.
    1. Wu DC, Hsu PI, Wu JY, et al. Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol Hepatol. 2010;8:36–41.e1. doi: 10.1016/j.cgh.2009.09.030.
    1. Sirimontaporn N, Thong-Ngam D, Tumwasorn S, Mahachai V. Ten-day sequential therapy of Helicobacter pylori infection in Thailand. Am J Gastroenterol. 2010;105:1071–1075. doi: 10.1038/ajg.2009.708.
    1. Yakoob J, Abid S, Abbas Z, Jafri SN. Antibiotic susceptibility patterns of Helicobacter pylori and triple therapy in a high-prevalence area. Br J Biomed Sci. 2010;67:197–201.
    1. Hsu PI, Wu DC, Wu JY, Graham DY. Is there a benefit to extending the duration of Helicobacter pylori sequential therapy to 14 days? Helicobacter. 2011;16:146–152. doi: 10.1111/j.1523-5378.2011.00829.x.
    1. Malfertheiner P, Bazzoli F, Delchier JC, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 2011;377:905–913. doi: 10.1016/S0140-6736(11)60020-2.
    1. Mahachai V, Sirimontaporn N, Tumwasorn S, Thong-Ngam D, Vilaichone RK. Sequential therapy in clarithromycin-sensitive and -resistant Helicobacter pylori based on polymerase chain reaction molecular test. J Gastroenterol Hepatol. 2011;26:825–828. doi: 10.1111/j.1440-1746.2011.06660.x.
    1. Molina-Infante J, Romano M, Fernandez-Bermejo M, et al. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology. 2013;145:121–128.e1. doi: 10.1053/j.gastro.2013.03.050.
    1. World Health Organization (WHO) What is an “organized” screening programme [Internet] Geneva: WHO; 2015. [cited 2015 Dec 8]. Available from: .
    1. Liou JM, Chen CC, Chang CY, et al. Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial. J Antimicrob Chemother. 2013;68:450–456. doi: 10.1093/jac/dks407.
    1. Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut. 2010;59:1143–1153. doi: 10.1136/gut.2009.192757.
    1. Briggs AH, Goeree R, Blackhouse G, O’Brien BJ. Probabilistic analysis of cost-effectiveness models: choosing between treatment strategies for gastroesophageal reflux disease. Med Decis Making. 2002;22:290–308. doi: 10.1177/027298902400448867.
    1. Lee YC, Lin JT, Wu HM, et al. Cost-effectiveness analysis between primary and secondary preventive strategies for gastric cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:875–885. doi: 10.1158/1055-9965.EPI-06-0758.
    1. Parsonnet J, Harris RA, Hack HM, Owens DK. Modelling cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: a mandate for clinical trials. Lancet. 1996;348:150–154. doi: 10.1016/S0140-6736(96)01501-2.
    1. Fendrick AM, Chernew ME, Hirth RA, Bloom BS, Bandekar RR, Scheiman JM. Clinical and economic effects of population-based Helicobacter pylori screening to prevent gastric cancer. Arch Intern Med. 1999;159:142–148. doi: 10.1001/archinte.159.2.142.
    1. Harris RA, Owens DK, Witherell H, Parsonnet J. Helicobacter pylori and gastric cancer: what are the benefits of screening only for the CagA phenotype of H. pylori? Helicobacter. 1999;4:69–76. doi: 10.1046/j.1523-5378.1999.98057.x.
    1. Mason J, Axon AT, Forman D, et al. The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial. Aliment Pharmacol Ther. 2002;16:559–568. doi: 10.1046/j.1365-2036.2002.01204.x.
    1. Roderick P, Davies R, Raftery J, et al. Cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease, using simulation. J Med Screen. 2003;10:148–156. doi: 10.1258/096914103769011067.
    1. Wang Q, Jin PH, Lin GW, Xu SR, Chen J. Cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: Markov decision analysis. Zhonghua Liu Xing Bing Xue Za Zhi. 2003;24:135–139.
    1. Xie F, Luo N, Lee HP. Cost effectiveness analysis of population-based serology screening and (13)C-Urea breath test for Helicobacter pylori to prevent gastric cancer: a markov model. World J Gastroenterol. 2008;14:3021–3027. doi: 10.3748/wjg.14.3021.
    1. Xie F, O’Reilly D, Ferrusi IL, et al. Illustrating economic evaluation of diagnostic technologies: comparing Helicobacter pylori screening strategies in prevention of gastric cancer in Canada. J Am Coll Radiol. 2009;6:317–323. doi: 10.1016/j.jacr.2009.01.022.
    1. Yeh JM, Kuntz KM, Ezzati M, Goldie SJ. Exploring the cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer in China in anticipation of clinical trial results. Int J Cancer. 2009;124:157–166. doi: 10.1002/ijc.23864.
    1. Ford AC, Forman D, Bailey AG, Axon AT, Moayyedi P. A community screening program for Helicobacter pylori saves money: 10-year follow-up of a randomized controlled trial. Gastroenterology. 2005;129:1910–1917. doi: 10.1053/j.gastro.2005.09.016.
    1. Chow WH, Blaser MJ, Blot WJ, et al. An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res. 1998;58:588–590.
    1. Chen Y, Blaser MJ. Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis. 2008;198:553–560. doi: 10.1086/590158.
    1. Wu MS, Lee WJ, Wang HH, Huang SP, Lin JT. A case-control study of association of Helicobacter pylori infection with morbid obesity in Taiwan. Arch Intern Med. 2005;165:1552–1555. doi: 10.1001/archinte.165.13.1552.
    1. Papamichael K, Konstantopoulos P, Mantzaris GJ. Helicobacter pylori infection and inflammatory bowel disease: is there a link? World J Gastroenterol. 2014;20:6374–6385. doi: 10.3748/wjg.v20.i21.6374.
    1. Perry S, de Jong BC, Solnick JV, et al. Infection with Helicobacter pylori is associated with protection against tuberculosis. PLoS ONE. 2010;5:e8804. doi: 10.1371/journal.pone.0008804.
    1. Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology. 2015;148:719–731.e3. doi: 10.1053/j.gastro.2015.01.040.
    1. Lee YC, Yen AM, Tai JJ, et al. The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease. Gut. 2009;58:174–181. doi: 10.1136/gut.2008.162305.
    1. Yaghoobi M, Farrokhyar F, Yuan Y, Hunt RH. Is there an increased risk of GERD after Helicobacter pylori eradication? A meta-analysis. Am J Gastroenterol. 2010;105:1007–1013. doi: 10.1038/ajg.2009.734.
    1. Wald NJ, Hackshaw AK, Frost CD. When can a risk factor be used as a worthwhile screening test? BMJ. 1999;319:1562–1565. doi: 10.1136/bmj.319.7224.1562.
    1. Dan YY, So JB, Yeoh KG. Endoscopic screening for gastric cancer. Clin Gastroenterol Hepatol. 2006;4:709–716. doi: 10.1016/j.cgh.2006.03.025.
    1. Shiotani A, Cen P, Graham DY. Eradication of gastric cancer is now both possible and practical. Semin Cancer Biol. 2013;23(6 Pt B):492–501. doi: 10.1016/j.semcancer.2013.07.004.
    1. Rugge M, Correa P, Di Mario F, et al. OLGA staging for gastritis: a tutorial. Dig Liver Dis. 2008;40:650–658. doi: 10.1016/j.dld.2008.02.030.
    1. Guyatt GH, Oxman AD, Vist G, et al. GRADE guidelines: 4. rating the quality of evidence: study limitations (risk of bias) J Clin Epidemiol. 2011;64:407–415. doi: 10.1016/j.jclinepi.2010.07.017.
    1. Choi HS, Lee SY, Kim JH, et al. Combining the serum pepsinogen level and Helicobacter pylori antibody test for predicting the histology of gastric neoplasm. J Dig Dis. 2014;15:293–298. doi: 10.1111/1751-2980.12144.
    1. Fock KM, Graham DY, Malfertheiner P. Helicobacter pylori research: historical insights and future directions. Nat Rev Gastroenterol Hepatol. 2013;10:495–500.

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