Introduction
Gastric cancer (GC) is a major cause of cancer-related deaths worldwide. According to global cancer statistics,1 1,089,103 new cases of GC and 768,793 related deaths occurred in 2020, ranking fifth and third for cancer incidence and mortality, respectively. In China, GC causes a leading burden of 0.40 to 0.47 million deaths per year.2,3 Over the last few decades, several key risk factors for the development of GC have been identified, including tobacco use, high salt intake, older age, and a family history of GC. Among these factors, Helicobacter pylori infection has been identified as the most important preventable and controllable risk factor owing to the nature of this highly virulent bacterium being able to be detected and treated, as emphasized in multiple international consensus reports.4–6 In fact, China has a high prevalence of both H. pylori infection and GC. More than 40% (478,508 of 1,089,103) of GC cases worldwide were identified in China, which is alarmingly high given that China accounts for only 25% of the world’s population. The fact that the H. pylori infection rate is 44% in the general Chinese population further confirms this trend. The high concordance of H. pylori-prevalent areas having high cancer incidence provides significant potential benefits and valuable opportunities to implement national GC prevention and control initiatives.
Although there exists substantial, high-quality research elaborating the effect and affordability of different GC prevention approaches, few systematic reviews have been performed to synthesize trial results and provide definite conclusions based on dynamic epidemiological changes in China. In this article, we aim to synthesize the latest evidence on the rationale of H. pylori management, the effect of various H. pylori management, and various established H. pylori management approaches. We hope our results will help focus future research directions and inform policy-making on GC prevention in China, as well as in other countries carrying a high cancer burden in the foreseeable future.
Rationale of H. pylori eradication for GC prevention
The relationship between H. pylori and stomach-related diseases has been a focus of gastroenterologists since its discovery by Barry J Marshall and J. Robin Warren in 1983.7 The Correa cascade, a stepwise progression from atrophy to metaplasia, dysplasia, and ultimately gastric adenocarcinoma initiated by H. pylori infection, provides a useful framework for understanding the carcinogenic mechanisms involved.8 In fact, most clinical investigations into the relationship between H. pylori and GC can be divided into three main topics (Fig. 1): (1) examining the correlation between H. pylori infection and GC, (2) assessing whether eradication of H. pylori can prevent the development of GC, and (3) determining the feasibility of eradicating H. pylori on a population scale as a preventive measure against GC.
Does H. pylori infection lead to GC (correlation between H. pylori infection and GC)?
During the period from the 1980s to the 2000s, numerous studies have directly or indirectly indicated a causal relationship between H. pylori infection and GC. For instance, in animal model trials in 1998, Watanabe9 reported that 37% of Mongolian gerbils orally inoculated with H. pylori developed GC within 62 weeks. Epidemiological studies10 conducted in 1991 also suggested that infection with H. pylori was associated with a 3.6-fold increased risk of GC, marking an important milestone in the understanding of H. pylori. Currently, it is recognized that up to 89% of noncardia gastric cancer cases can be attributed to chronic H. pylori infection,11 while H. pylori-negative GC accounts for only 0.4–2.3% of cases.12 This valuable recognition is intricately connected with relevant studies conducted during the late 20th century.
Could H. pylori eradication counteract the progression of precancerous lesions and block the development of GC?
In the 21st century, as consensus was reached regarding the carcinogenic potential of H. pylori, academic attention of medical specialists has gradually shifted to the effectiveness of H. pylori eradication on GC prevention, both for clinical utility and public health considerations. A number of high-quality randomized controlled trials (RCTs) were initiated in China (Yantai,13 Shandong,14 Fujian,15 Taiwan16), and Korea,17 and after years of follow-up, most of the findings were published between 2010 and 2020. As research deepened, understanding of the benefits of H. pylori eradication can be broadly divided into two stages.
Firstly, H. pylori treatment can block the progression of precancerous disease along the stepwise inflammatory pathway. A randomized double-blind, placebo-controlled trial13 in China with 435 farmers infected with H. pylori, randomized to either therapy or placebo groups, demonstrated that treatment of H. pylori is protective against premalignant gastric lesions progression over a median of 10 years of follow-up. Gastric precancerous disease can also be reversed to lower-level lesions or even normal mucosa, as shown by a mass H. pylori chemoprevention program on Taiwan Matsu Island.18 In this community-based study, the prevalence of gastric atrophy in 1,762 residents declined from 59.9% in 2004 (immediately before eradication) to 13.7% in 2008 (4 years after intervention), yielding an effectiveness of 77.2% in reversing gastric atrophy. Prior to 2017, the generally accepted point-of-no-return theory stated that by H. pylori eradication, the histological severity of intestinal metaplasia (IM) or dysplasia could not be reduced, nor the progression toward GC be halted or reversed, with this view adopted by the Maastricht consensus.4 However, studies with longer follow-up periods have demonstrated significant regression in IM. Extending the follow-up period from 4 to 14 years for the previously mentioned mass eradication study in Matsu Island16 revealed a decrease in the prevalence rates of both early and advanced-stage IM from 31.7 to 21.4% and from 11.8 to 1.8%, respectively. A subsequent meta-analysis19 supported this conclusion, which has now been accepted in the guideline of latest version.20 The development of GC involves a complex and protracted evolution over several years. Although studies with longer follow-up periods are more challenging to conduct due to financial and medical limitations, they typically yield more objective and robust conclusions, providing a more comprehensive understanding of disease progression and treatment efficacy.
Secondly, eradication of H. pylori has been shown to reduce the incidence of GC. In recent years, several high-quality meta-analyses have assessed the benefits of H. pylori eradication in preventing GC (Table 1).21–27 These studies, with low heterogeneity, consistently demonstrate H. pylori eradication has a strong preventive effect on GC, with relative risks ranging from 0.46 to 0.66 for both primary and metachronous cancer. Ford’s conclusion,21 although limited to three trials, further indicates that H. pylori eradication not only reduces the incidence of GC, but also leads to a decrease in disease-specific mortality. This finding highlights the importance of H. pylori treatment as a preventive measure and suggests directions for future investigations. In this section, the argument regarding the “point of unstoppable” persists, as demonstrated by Chen et al.22 that eradication of H. pylori in lesions have progressed to IM does not significantly reduce the incidence of GC. However, Sugano study23 found the benefit of eradication was strongly correlated with time to eradication, and the reduction in incidence after eradication was significantly greater (p = 0.01) in groups with long-term (> 5 years) follow-up (odds ratio of 0.32) compared with those with shorter follow-up (< 5 years). Hence, confirming the potential benefit of H. pylori eradication for preventing GC in IM patients is still required. It is important to note that most of the studies included in the current meta-analyses were conducted in East Asia. Given the variability of GC heterogeneity by ethnicity in multi-ethnic societies, caution should be exercised when extrapolating above conclusions in other populations without sufficient evidence.
Table 1High-quality meta-analysis evaluating the association between Helicobacter pylori eradication and GC development
| First author, year | Country | Database (timespan) | Sample size | Study inclusion | Enrolled targets | GC incidence
| GC mortality
|
|---|
| Effect | RR | Heterogeneity | Effect | RR | Heterogeneity |
|---|
| Ford AC, 201424 | UK | Medline (1946–2013); Embase (1947–2013); Cochrane central register | 6,497 | 6 RCTs | Healthy asymptomatic infected Asian adults | 1.6% vs. 2.4% | 0.66 | I2 = 0% | | NA | |
| Ford AC(a), 202021 | UK | MEDLINE (1947 to February 2020); Embase and Embase Classic (1947 to February 2020); Cochrane central register | 8,323 | 7 RCTs | Healthy asymptomatic infected adults | 1.6% vs. 3.0% | 0.54 | I2 = 0% | 1.14% vs. 1.87% | 0.61 | I2 = 0% |
| Ford AC(b), 202021 | UK | Same as above | 1,841 | 3 RCTs | Individuals after GC resection | 4.5% vs. 9.3% | 0.49 | I2 = 0% | NA | | |
| Chen HN, 201622 | China | MEDLINE, EMBASE, Cochrane Library (up to March 2014) | 7,955 | 8 RCTs | Individuals with normal mucosa or precancerous lesions | 1.9% vs. 2.9% | 0.64 (< IM RR = 0.25); (≥ IM RR = NS) | I2 = 0% | | | |
| Sugano K, 201923 | Japan | MEDLINE and Ichushi-Web (up to December 2016) | 31,106 | 32 (RCTs and cohort studies) | Individuals with normal mucosa, precancerous lesions, peptic ulcer, or GC undergone resection | 1.9% vs. 3.6% | 0.46 | I2 = 15% | | | |
| Lee YC, 201625 | China (Taiwan) | PubMed, Cochrane Library, ClinicalTrials.gov (up to May 2015) | 48,064 | 24 (8 RCTs and 16 cohort studies) | Individuals with normal mucosa or after GC resection | 1.2% vs. 1.7% | 0.54 | I2 = 0% | | | |
| Doorakkers E, 201626 | Sweden | PubMed, Web of Science, Embase, and Cochrane Library (up to November 2015) | 31,544 | 9 (1 RCT and 8 cohort studies) | General population | 0.9% vs. 1.1% | 0.46 | I2 = 32.3% | | | |
| Duan F, 201927 | China | MEDLINE, PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang (January 1997 to January 2017) | 40,740 | 13 (4 RCTs and 9 cohort studies) | Individuals with normal mucosa or precancerous lesions | 0.13% vs. 0.14% | 0.52 | I2 = 0% | | | |
Is it feasible to eradicate H. pylori on a population scale to prevent GC?
Clarifying the effectiveness of H. pylori eradication in preventing GC serves as a strong basis to support population-wide strategies as policy recommendations. The Taipei Consensus28 published in 2020 discussed the feasibility of population-based screening, marking the gradual emergence of population-based screening as a mainstream issue for policy makers. However, a variety of factors must be considered when initiating a universal H. pylori screening program.
Target countries or areas
Mass screening for H. pylori infection should prioritize countries or regions with a high burden of both H. pylori infection and GC, since programs in highly H. pylori-infected regions could obtain higher screening efficiency and additional health benefits by identifying more H. pylori-infected participants with equal number of tests conducted. However, the carcinogenic effect of H. pylori infection does not show uniformity across global regions but is influenced by various factors, such as ethnicity and the type of infected strain. African and certain Asian countries, such as India, exhibit a high prevalence of H. pylori infection ranging from 63.5 to 87.7%,29 surpassing the global average of 44.3%30; but their age-standardized GC incidence (4.5 per 100,000) is significantly lower than the world average of 11.10/100,000.1 Population-wide eradication is only necessary and feasible in areas where H. pylori infection is clearly carcinogenic, that is, where both H. pylori infection and GC incidence are remaining in high levels. East Asia is known for its high incidence of GC; in particular, nearly 40% of GC cases seen globally occurred in China,1 a typical country of both H. pylori and GC prevalence. A recent decision analysis synthesizing data from China’s latest epidemiological surveys and trial results concluded that implementing a universal eradication program for H. pylori would be cost effective in reducing the cancer burden in the long term.31 This program may serve as a reference for other countries or regions with similar epidemiological conditions. Recently, an effect of H. pylori eradication on the incidence of noncardia gastric adenocarcinoma was observed in a large diverse population in the USA.32 In 716,567 individuals with a history of H pylori testing and/or treatment, the adjusted subdistribution hazard ratios (HRs) and 95% confidence intervals (CIs) of GC for H pylori-positive/untreated and treated individuals were 6.07 (4.20–8.76) and 2.68 (1.86–3.86), respectively, compared with H pylori-negative individuals.
Target populations
Different demographic characteristics of the target population can result in varying levels of benefit. Health economics evaluations33,34 have consistently shown that H. pylori screening at a younger age (20–40 years) is more cost-effective owing to the higher efficacy of GC prevention. This can be attributed to the degree of mucosal damage at the time of intervention. H. pylori infection primarily occurs during childhood and adolescence and tends to persist in the absence of external intervention. Therefore, the age of the patient is considered an indicative factor of the duration of the infection and the extent and severity of the damage to the gastric mucosa. In 2016, a meta-analysis22 consisting of 7,955 subjects concluded that after H. pylori eradication therapy, the relative risk of GC decreased by 12% in 2,115 participants with IM at baseline compared to controls, and by 75% in 1,337 participants without precancerous lesions or with only atrophy, indicating early eradication of H. pylori during the early stages of mucosal damage provides the greatest benefit. In other words, the earlier the eradication of H. pylori, the greater the benefit.
Although severe damage, such as advanced-stage IM and extensive dysplasia, is more commonly observed in older individuals, there are still significant benefits to performing H. pylori eradication in this population. A retrospective study conducted in Hong Kong, China, involving 73,237 patients who had undergone H. pylori eradication and were followed up for 7.6 years, revealed that the risk of GC was reduced by 18% among individuals over 60 years of age. Therefore, the eradication of H. pylori in elderly patients is to be encouraged.
Improving the eradication success rate
Effective control of GC relies on successful eradication of H. pylori. An RCT15 conducted in Fujian, China in 2022 showed failure of first-line H. pylori therapy did not result in a statistically significant benefit in preventing GC over a 26.5-year follow-up period (HR = 0.46, p = 0.289) compared with those who achieved successful treatment (HR = 0.46, p = 0.009). Based on the experience gained from extensive screening initiatives,17,35,36 the current success rate of eradicating H. pylori infection is limited, ranging from 70.1 to 78.2%, with considerable potential for further enhancement. Scientific and effective selection of first-line treatment regimens, along with timely adjustments based on regional variations, can significantly offset these deficiencies, and this is particularly crucial given the primary resistance rates to clarithromycin, metronidazole, and levofloxacin exceeding 15% in all regions.37 As outlined in the VI consensus report,20 the first-line algorithm for empirical H. pylori eradication in areas with low clarithromycin resistance includes bismuth quadruple therapy [proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole] and clarithromycin triple therapy (PPI, clarithromycin, and amoxicillin). In areas with high (> 15%) clarithromycin resistance, the recommended first-line treatments are bismuth quadruple therapy and nonbismuth quadruple therapy (PPI, clarithromycin, amoxicillin, and metronidazole). Triple therapy based on potassium-competitive acid blockers (also referred to as P-CAB) also demonstrated promising results in achieving high eradication rates among patients infected with clarithromycin-resistant strains.38 Meanwhile, regular monitoring of treatment efficacy in at least a subset of the population is crucial for timely adjustment of the regimen before resistance compromises therapy effects, as empirical therapy failing to achieve a cure rate of at least 90% should be abandoned.39
The failed eradication of H. pylori has become a growing concern because of the continuous increase in antibiotic resistance rates. The latest Chinese national guideline on H. pylori40 recommends treatment based on the patient’s history of antibiotic use in empirical treatment and the utilization of antibiotic sensitivity tests (ASTs) in individuals with a previous history of treatment failure. Data from China41–43 suggests that personalized therapy guided by ASTs has a higher eradication rate compared with empirical treatment regimens, resulting in an average increase of 56–126 successful eradication cases per 1,000 patients. For refractory H. pylori infection (unsuccessful eradication after two consecutive standardized eradication treatments), the use of low-resistance antibiotics such as tetracycline and furazolidone yields better eradication outcomes.40
Compliance considerations
While symptomatic patients with H. pylori infection are more likely to undergo voluntary eradication, the majority of H. pylori-infected individuals from population screening programs are asymptomatic. This presents a significant challenge to the adherence of H. pylori management. For example, the implementation of a large-scale H. pylori screening program in Taiwan revealed that 20% of participants (3,764 of 18,821) did not respond to an invitation for a 13C-urea breath test (13C-UBT), and 17.31% of H. pylori-infected patients (5,493 of 6,643) refused the eradication therapy.44 Another study demonstrated that 10% of patients prescribed H. pylori eradication regimen failed to take even 60% of their medications.45 Consequently, ensuring compliance with screening and treatment protocols needs to be emphasized. (1) Compliance with H. pylori screening: Noninvasive screening tests, such as the 13C-UBT, Helicobacter pylori stool antigen (HpSA) test, and serology testing, can help mitigate negative emotions and resistance to treatment. The 13C-UBT is the most precise noninvasive screening method, but it necessitates fasting prior to testing and a 30 m wait between two expirations. Although serology tests are the most convenient, they are not able to differentiate between current and previous infections. The HpSA test is less commonly used for screening and is not well-received by the general population. Also, H. pylori infection status can be accurately assessed by magnetic controlled capsule endoscopy.46 (2) Compliance with H. pylori therapy: The willingness to receive antibiotic therapy and the ability to adhere to the prescribed regimen are prerequisites for effective eradication. However, the incidence of short-term adverse events during treatment may discourage patients from receiving treatment, leading to lower levels of compliance.47 The European Registry on H. pylori management conducted a prospective analysis of 22,492 patients who underwent eradication therapy and found that 23% of the patients experienced at least one adverse event during medication. The most common adverse reactions observed were taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%).48 Notably, the classic bismuth-based quadruple therapy regimen, which is widely used worldwide, was associated with a higher incidence of side effects of 37%. At the same time, long-term adverse events, such as antimicrobial resistance, constitute a potential concern for treated patients. (3) Compliance with follow-up retesting: In the context of increasing drug resistance, post-treatment retesting is becoming increasingly important. A negative test result would be considered as the official endpoint of treatment process. According to the fifth edition of the Chinese consensus on H. pylori eradication,49 retesting should be performed 4–6 weeks after medication cessation to minimize the impact of residual drugs (such as PPIs, bismuth, and antibiotics) on test results.
Active promotion of knowledge about H. pylori, including its potential gastrointestinal (GI) and extra-GI harms, as well as the benefits of eradication therapy, could be an effective approach to improving compliance among the public.50 Specific ways to conduct public education include strengthening publicity through mass media and providing health education at the community and individual level. Physicians-targeted education is also important, as study found significant proportion (more than 30%) of physicians may have incorrect knowledge or inappropriate use of eradication regimens and antibiotic combinations.48 Ensuring patients receive the appropriate treatments would be a powerful tool in overcoming public skepticism.
Existing H. pylori management strategies
In 1997, gastroenterologists from the European Helicobacter Study Group suggested performing H. pylori testing in patients over 45 years old who have dyspeptic symptoms. This recommendation was later established as a “test and treat strategy” in the Maastricht III consensus (Table 2),5,51,52,53,54 which was published in 2007. The strategy does not necessitate physicians to engage in community-based surveillance to identify infected patients. Instead, it relies on testing patients who present to the hospital with GI symptoms for H. pylori infection and is therefore categorized as a passive screening measure. Despite the recommendation for implementing the strategy in highly infected areas, it has a limited target audience and efficacy in meeting the needs for H. pylori eradication in highly infected countries, and is unable to provide a sufficiently powerful intervention for reducing population infection levels.
Table 2Comparison of existing Helicobacter pylori management strategies
| Strategy | Test and treat | Screen and treat (also called “search and screen” strategy) | Family-based control and management |
|---|
| Aims | GC prevention and dyspeptic symptom control | GC prevention | GC prevention and intrafamily spread interruption |
| Target populations | Uninvestigated dyspeptic patients with no alarm symptoms | Populations with a high incidence or high risk of GC. intermediate or high incidence of GC. | Cohabitants and family members of H. pylori-infected patients |
| Target areas | H. pylori-prevalent regions (>20%) | Incidence of GC higher than 15–20 per 100,000. | Both high and low prevalent regions |
| Type of strategy | Passive | Active | Either active or passive |
| Recurrence | Moderate | Moderate | Low |
| Eradication rates | >80% | >80% | >90% |
| Cancer prevention effect | Low to Moderate | High | Moderate to high |
| Cost | Low | High | Moderate |
| Benefit-cost ratio | Moderate to high | Moderate to high | High |
| Compliance | Moderate | Moderate | Potentially high (awaiting evidence) |
| H. pylori detection ability | Moderate | Moderate | Moderate (slightly higher) |
| Formal inception, year | Maastricht II53 and III51 Consensus Report, 2000–2006 | Maastricht IV Consensus Report5 and Kyoto global consensus report,54 2006–2015 | Chinese Consensus Report on Family-Based H. pylori Infection,52 2022 |
The 2012 Maastricht IV Consensus5 proposed a screen and treat strategy (Table 2) to effectively address the aforementioned issues by expanding the screening audience from solely outpatients to the entire population of a given region. In contrast to the test and treat approach, which depends on patients seeking care at clinics, this strategy involves policymakers making deliberate efforts to search and detecting H. pylori carriers within the community, making it an active screening strategy. Population-based mass eradication programs for H. pylori have been implemented in various regions, including Japan,55 mainland China,35 and Taiwan,16 using both invasive testing (endoscopy) and noninvasive methods (e.g., 13C-UBT). For example, from 2004 to 2018, a large-scale H. pylori screening program was conducted in Ma Zu, resulting in a notable reduction in the H. pylori prevalence from 64.2% to 15.0% in the local population.16 Furthermore, this program led to a significant decrease in the incidence and mortality of GC by 53% and 25%, respectively, providing compelling evidence to confirm the effectiveness of “screen and treat” strategy in cancer prevention.
China is a vast country with a population of more than 1.4 billion individuals and nearly 500 million households, as per the seventh National Census.56 Achieving population-wide H. pylori eradication often requires years or decades and re-infection among the selected population would be inevitable during the lengthy process of screening implementation if the screen and treat strategy is directly applied in China. In addition, the significant regional variation of infection rates across the country combined with the uneven distribution of medical resources, further weakens the feasibility of this strategy.
In 2021, a group of Chinese scholars proposed a novel approach,52 a family-based H. pylori management strategy (Table 2), to prevent and control H. pylori infection at the community level. It supplements the first two existing strategies and focuses on countries with high rates of GC and limited per capita resources. This approach is not designed to function autonomously from the previous two strategies, but rather serves to enhance their efficacy and applicability in real-world settings. The family strategy, integrated with the test and treat approach, encompasses screening, treatment, and follow-up care for family members after identifying an H. pylori-carrier during outpatient visit, with aims to enhance family engagement, awareness, and contain the probability of bacterial transmission within the household. When used in conjunction with the screen and treat approach, the family screening strategy entails modifying the basic H. pylori screening unit from individuals to the entire family, with all family members being screened before moving on to the next household. The primary difference between family-based screening and conventional strategies lies in the order of individual screening during the procedure, despite the ultimate objective being unchanged of testing the entire population.57 The latest guideline from China provided feasible eradication treatment for completing the family screening strategy.40 Also, compared with a genetic cause, H. pylori has a larger role in GC development.58
The advantages of family-based strategy (Table 2) are: (1) Applicability in both high and low infection areas. The phenomenon of H. pylori family clustering has been demonstrated in various regions worldwide,58–61 indicating the universal suitability of the family-based strategy across regions and ethnicities. (2) Blocking intrafamily transmission. Eliminating the source of H. pylori infection in households can reduce the risk of children acquiring the bacterium and provide long-term benefits to newborns. A meta analysis62 confirmed that H. pylori family management strategies have higher success rates in eradicating H. pylori infection and lower rates of recurrence compared with traditional individual-based approaches. (3) Higher patient compliance, as family management strategies are intrinsically linked to the health of household members and cohabitants, trial participants may exhibit greater enthusiasm and higher levels of compliance for undergoing screening. This may lead to a swifter implementation of the program. (4) Higher cost-effectiveness, according to a health economics analysis, family-based strategies were more cost-effective than screen-and-treat strategies, with a cost of $9.18 per quality-of-life year gained, as opposed to $12.08 for the latter.63 (5) Better H. pylori detection, as the efficiency of screening would be enhanced by searching along the H. pylori intrafamilial transmission chain, compared with random selection. The family-based strategy has a potentially higher yield for detecting H. pylori-infected individuals, with approximately 4.02% more infections identified with equal numbers of tests conducted.64
Conclusions
GC is a preventable disease, and H. pylori infection is the most important controllable risk factor, serving as an essential step toward effective prevention and control of GC. Despite numerous studies confirming that eradicating H. pylori reduces the risk of GC, there remains a significant gap between fundamental and clinical knowledge and public health interventions. A family-based approach to H. pylori management represents a novel strategy for future GC prevention and control, boasting numerous advantages and having the potential to play a crucial role in future policy making. In addition, secondary screening measures for GC based on H. pylori represent a critical focus of attention (Table 3).65–81 Both primary and secondary preventive strategies are crucial components of effective GC management. Much like the indispensable nature of both legs in bipedal locomotion, either strategy cannot be overlooked without compromising the overall efficacy of the treatment.
Table 3Screening models or strategies for GC that includes indicators of Helicobacter pylori infection
| Model | Country | Target population | Sample size | Indicators included in the model | Discrimination |
|---|
| Prediction models |
| Ikeda F, 201665 | Japan | General Japanese population | 2,446 | PG, H. pylori | 0.77 |
| Taninaga J, 201966 | | Healthy population | 1,431 | H. pylori serology testing and chronic atrophic gastritis, sex, age, and body mass index, white blood cell counts, neutrophil ratio, lymphocyte ratio, eosinophil ratio, monocyte ratio, basophil ratio, platelet count, hemoglobin, mean corpuscular volume, and hemoglobin A1c, gastric, or duodenal ulcers including scars, GERD, or Barrett’s esophagus and postgastrectomy | 0.736–0.874 |
| Charvat H, 201667 | Japan | Japanese residents | 19,028 | Age, family GC history, smoking, salted food, PG, H. pylori | 0.768 |
| Murphy JD, 202268 | USA | Healthy individuals across Japan, China, and Korea | 1,422 | Sex, age, UreA, Hp 0305, Hp 1564, PGs | 0.738 |
| Ishikura N, 202169 | Japan | Participants of the Hospital Epidemiology Research Program | 3,678 | Age, ABCD classification defined by H. pylori and PGs, smoking, alcohol consumption, fruit and vegetable intake, and 3 GWAS-identified SNP polymorphisms | 0.77–0.78 |
| Song M, 201870 | USA | Finnish male smokers | 21,895 | PGI, H. pylori | NA |
| Lee TY, 201571 | China | Patients with Peptic Ulcer Disease from Taiwan | 278,898 | Age, sex, ulcer site, ulcer complication, H. pylori eradication, NSAIDs duration, surveillance endoscopy | 0.78 |
| Diagnostic models |
| Tu, 201772 | China | Population from high GC mortality area | 9,002 | PGI, PGII, PGR, G-17, H. pylori IgG | 0.803 |
| Iida M, 201773 | Japan | General Japanese population | 2,444 | Age, sex, H. pylori and atrophic gastritis, Hemoglobin A1c, Current smoking | 0.79 |
| So JBY, 202174 | Singapore | Singapore Chinese population | 682 | miRNAs, Age, H. pylori, PG, CA199, CEA | 0.849–0.890 |
| Cai QC, 201975 | China | Chinese individuals with a ‘high risk’ of GC | 14,929 | Age, H. pylori, sex, pickled food, fried food, PG, G-17 | 0.73–0.76 |
| Tao W, 202076 | China | Chinese individuals with precancerous lesions | 383 | Age, sex, tap water drinking, H. pylori infection, GC family history, PGs | |
| Park CH, 201677 | Japan | Consecutive Japanese patients | 562 | Age, sex, PGs, H. pylori | NA |
| Liu MM, 201878 | China | Patients with gastric diseases | 620 | 34 variables including age, BMI, sex, H. pylori infection | 0.62–0.74 |
| Ji L, 202079 | China | General residents | 7,773 | Positive family history of GC in first-degree relatives, PG, H. pylori, age | NA |
| Lin JT, 199580 | China | Subjects underwent endoscopy from Taiwan | 686 | Peptic ulcer, PGI, H. pylori | 0.84 |
| Kaise M, 201181 | Japan | Medical health checkup population | 1,446 | TFFs, PGs, H. pylori | 0.812–0.893 |
Abbreviations
- 13C-UBT:
13C-urea breath test
- AST:
antibiotic sensitivity tests
- GC:
gastric cancer
- GI:
gastrointestinal
- HpSA:
Helicobacter pylori stool antigen
- HR:
hazard ratio
- IM:
intestinal metaplasia
- P-CAB:
potassium-competitive acid blockers
- PPI:
proton pump inhibitor
- RCT:
randomized controlled trial
Declarations
Funding
This investigation was supported by the grant from the three-year action plan for the construction of Shanghai’s public health system (2023–2025), key discipline construction project (GWVI-11.1-21), and 2020 Hainan Provincial Major Science and Technology Program (No. ZDKJ202005).
Conflict of interest
Prof. Zhaoshen Li has been an editor-in-chief of Cancer Screening and Prevention since August 2021. Prof Yiqi Du has been an executive associate editor of Cancer Screening and Prevention since December 2022. Xianzhu Zhou has no other conflict of interests related to this publication.
Authors’ contributions
Contributed to study concept and design (YD and ZL), acquisition of the data (XZ and YD), assay performance and data analysis (XZ and YD), drafting of the manuscript (XZ and YD), critical revision of the manuscript (YD and ZL), supervision (YD and ZL). All authors have made a significant contribution to this study and have approved the final manuscript.