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1
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Sun HT. Helicobacter pylori-related serum indicators: Cutting-edge advances to enhance the efficacy of gastric cancer screening. World J Gastrointest Oncol 2025; 17:100739. [PMID: 40092953 PMCID: PMC11866254 DOI: 10.4251/wjgo.v17.i3.100739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
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Affiliation(s)
- Hao-Tian Sun
- Cancer Institute, University College London, London WC1E 6BT, United Kingdom
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2
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Chang WL, Yeh YC, Sheu BS. The impacts of H. pylori virulence factors on the development of gastroduodenal diseases. J Biomed Sci 2018; 25:68. [PMID: 30205817 PMCID: PMC6131906 DOI: 10.1186/s12929-018-0466-9] [Citation(s) in RCA: 125] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 08/21/2018] [Indexed: 12/12/2022] Open
Abstract
Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.
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Affiliation(s)
- Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Yi-Chun Yeh
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan. .,Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
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3
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Li H, Zhang B, Hu X, Dong Y, Fan Q, Guo F, Ren X, Zhou H, Tian W, Zhao Y. Serum Helicobacter pylori FliD antibody and the risk of gastric cancer. Oncotarget 2017; 7:22397-408. [PMID: 26968951 PMCID: PMC5008368 DOI: 10.18632/oncotarget.7981] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 02/23/2016] [Indexed: 02/06/2023] Open
Abstract
FliD and CagA are important virulence factors of H. pylori. We aimed to evaluate the screening values of FliD and CagA for gastric cancer (GC). Serum samples were obtained from 232 cases and 266 controls in a case-control study. Unconditional multivariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs) was used to analyze the relationships between FliD, CagA and GC. The sensitivities, specificities and receiver operating characteristic (ROC) curves were calculated. Finally, the combined screening values of FliD, FlaA, NapA and CagA were assessed based on discriminant analysis. In all subjects, the associations of FliD and CagA with GC were evident with ORs (95% CIs) of 7.6 (4.7-12.3) and 2.5 (1.6-3.8), respectively (*p<0.001). The areas under ROC curves (AUCs) for FliD and CagA were 0.800 and 0.653, respectively. The AUC for the combination of FliD, FlaA and NapA was 0.915, which represented an increase of 0.115 over that of FliD alone (*p<0.001). These findings indicate that the FliD antibody is associated with GC and could exhibit high validity as a biomarker in screening for GC patients. The combination of FliD, FlaA and NapA improved the screening validity.
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Affiliation(s)
- Hailin Li
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Bing Zhang
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Xiaomeng Hu
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Yingzi Dong
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Qing Fan
- Xiangfang Center for Disease Control and Prevention, Harbin, Heilongjiang Province, P. R. China
| | - Fang Guo
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Xiyun Ren
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Haibo Zhou
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Wenjing Tian
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
| | - Yashuang Zhao
- Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China
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Matsuo Y, Kido Y, Akada J, Shiota S, Binh TT, Trang TTH, Dung HDQ, Tung PH, Tri TD, Thuan NPM, Tam LQ, Nam BC, Khien VV, Yamaoka Y. Novel CagA ELISA exhibits enhanced sensitivity of Helicobacter pylori CagA antibody. World J Gastroenterol 2017; 23:48-59. [PMID: 28104980 PMCID: PMC5221286 DOI: 10.3748/wjg.v23.i1.48] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 10/03/2016] [Accepted: 10/27/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To develop a novel Helicobacter pylori (H. pylori) CagA antibody enzyme-linked immunosorbent assay (ELISA) suitable for detecting serum anti-CagA antibodies with high sensitivity.
METHODS Recombinant East Asian-type CagA protein was purified and immobilized for ELISA. Serum samples from 217 Vietnamese individuals (110 H. pylori-infected and 107 uninfected individuals) were applied. Conventional ELISA from Western-type CagA and our East Asian-type CagA ELISA were evaluated by comparing 38 subjects with the Western-type genotype and 72 subjects with the East Asian-type cagA genotype. Histological scores of the gastric mucosa were determined using the updated Sydney System to examine the relationship with anti-CagA antibody titers.
RESULTS Recombinant 70-100 kDa fragments were immobilized on the ELISA plate. In ROC analysis, the area under the curve of our East Asian-type CagA ELISA was comparable to that of conventional CagA ELISA. The sensitivity of the two ELISAs differed depending on the cagA genotype. The sensitivity of East Asian-type CagA ELISA was higher for subjects infected with East Asian-type cagA H. pylori (P < 0.001), and the sensitivity of the conventional CagA ELISA tended to be higher for subjects infected with Western cagA H. pylori (P = 0.056). The titer of anti-CagA antibody tended to correlate with monocyte infiltration scores (r = 0.25, P = 0.058) and was inversely correlated with H. pylori density (r = -0.26, P = 0.043).
CONCLUSION The novel ELISA is useful to detect anti-CagA antibodies in East Asian countries, and the titer may be a marker for predicting chronic gastritis.
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Sekar D, Krishnan R, Thirugnanasambantham K, Rajasekaran B, Islam VIH, Sekar P. Significance of microRNA 21 in gastric cancer. Clin Res Hepatol Gastroenterol 2016; 40:538-545. [PMID: 27179559 DOI: 10.1016/j.clinre.2016.02.010] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 02/01/2016] [Accepted: 02/17/2016] [Indexed: 02/04/2023]
Abstract
Despite promising developments of treatment, the mortality due to gastric cancer remains high and the mechanisms of gastric cancer initiation and the development also remains elusive. It has been reported that patients with positive serologic tests for H. pylori have a higher risk of the development of gastric cancer. microRNAs (miRNAs) are short non-coding RNA molecules consisting of 21-25 nucleotides (nt) in length. The miRNAs silence their cognate target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3'-untranslated (UTR) regions and plays a very important role in cancer biology. Recent evidences indicate that miR-21 is overexpressed in tumour tissue, including gastric cancer and plays a vital role in tumour cell proliferation, apoptosis, invasion and angiogenesis. Elevated levels of miR-21 is associated with downregulation of tumour suppressor genes, such as programmed cell death 4 (PDCD4), tissue inhibitor of metalloproteinase 3, phosphatase and tensin homolog (PTEN), tropomyosin 1, ras homolog gene family member B, and maspin. Silencing of miR-21 through the use of a miR-21 inhibitor affected cancer cell viability, induced cell cycle arrest and increased chemosensitivity to anticancer agents indicating that miR-21 functions as an oncogene. Although an increased expression level of miR-21 has been observed in gastric cancer, studies related to the role of miR-21 in gastric cancer progression is very limited. The main thrust of this mini review is to explain the potency of miR-21 as a prognostic and/or diagnostic biomarker and as a new target for clinical therapeutic for interventions of gastric cancer progression.
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Affiliation(s)
- Durairaj Sekar
- Narayana Medical College and Hospital, Chintha Reddy Palem, Nellore 524002, India; Stem Cell Division, Cryovault Biotech India Pvt. Ltd, Bangalore 560016, India.
| | - Ramalingam Krishnan
- Narayana Medical College and Hospital, Chintha Reddy Palem, Nellore 524002, India
| | | | - Baskaran Rajasekaran
- Biochemistry and Molecular Biology, Pondicherry University, RV Nagar, Pondicherry 6-5014, India
| | | | - Punitha Sekar
- Stem Cell Division, Cryovault Biotech India Pvt. Ltd, Bangalore 560016, India
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6
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Wang YK, Kuo FC, Liu CJ, Wu MC, Shih HY, Wang SSW, Wu JY, Kuo CH, Huang YK, Wu DC. Diagnosis of Helicobacter pylori infection: Current options and developments. World J Gastroenterol 2016. [PMID: 26523098 DOI: 10.3748/wjg.v21.i40.11221.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2022] Open
Abstract
Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.
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Affiliation(s)
- Yao-Kuang Wang
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Fu-Chen Kuo
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Chung-Jung Liu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Meng-Chieh Wu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Hsiang-Yao Shih
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Sophie S W Wang
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Jeng-Yih Wu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Chao-Hung Kuo
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Yao-Kang Huang
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Deng-Chyang Wu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
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Cai H, Ye F, Michel A, Murphy G, Sasazuki S, Taylor PR, Qiao YL, Park SK, Yoo KY, Jee SH, Cho ER, Kim J, Chen SC, Abnet CC, Tsugane S, Cai Q, Shu XO, Zheng W, Pawlita M, Epplein M. Helicobacter pylori blood biomarker for gastric cancer risk in East Asia. Int J Epidemiol 2016; 45:774-81. [PMID: 27170766 DOI: 10.1093/ije/dyw078] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2016] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Incidence and mortality rates for gastric cancer, the fifth most commonly diagnosed and third most deadly cancer worldwide, are highest in East Asia. We sought to identify gastric cancer risk biomarkers among eight prospective studies from China, Japan and Korea. METHODS This pooled nested case-control study included 1608 incident non-cardia gastric cancer cases and 1958 matched controls. Pre-diagnostic antibody levels to 15 Helicobacter pylori proteins were assessed using multiplex serology. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Sero-positivity to 10 H. pylori antigens (Omp, CagA, VacA, HcpC, HP 0305, GroEL, NapA, HyuA, Cad, HpaA) was associated with a 1.29- to 3.26-fold increase in odds of gastric cancer. Omp and HP 0305 consistently remained associated with gastric cancer risk after mutually adjusting for all other markers. Sero-positivity to both Omp and HP 0305 was associated with an over 4-fold increase in gastric cancer incidence (OR, 4.09; 95% CI 3.26-5.13). When limited to only those who are CagA+ H. pylori+, Omp/HP 0305 sero-positivity remained strongly associated with an over 3-fold increase in the odds of gastric cancer (OR, 3.34; 95% CI 2.27-4.91). The results were highly consistent among the cohorts. CONCLUSIONS We have confirmed new H. pylori biomarkers that are strongly associated with gastric cancer risk, even among those infected with the known H. pylori virulence factor CagA. These results may help to design cost-efficient prevention strategies to reduce gastric cancer incidence in East Asia.
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Affiliation(s)
- Hui Cai
- Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center
| | - Fei Ye
- Vanderbilt Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Angelika Michel
- Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DFKZ), Heidelberg, Germany
| | - Gwen Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Shizuka Sasazuki
- Epidemiology and Prevention Group, National Cancer Center, Tokyo, Japan
| | - Philip R Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - You-Lin Qiao
- Department of Cancer Epidemiology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sue K Park
- Cancer Research Institute, Department of Biomedical Sciences and Department of Preventive Medicine
| | - Keun-Young Yoo
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sun Ha Jee
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, Yonsei University, Seoul, Korea
| | - Eo Rin Cho
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, Yonsei University, Seoul, Korea
| | - Jeongseon Kim
- Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea
| | - Sheau-Chiann Chen
- Vanderbilt Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christian C Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, National Cancer Center, Tokyo, Japan
| | - Qiuyin Cai
- Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center
| | - Xiao-Ou Shu
- Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center
| | - Wei Zheng
- Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center
| | - Michael Pawlita
- Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DFKZ), Heidelberg, Germany
| | - Meira Epplein
- Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center
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Abdi E, Latifi-Navid S, Yazdanbod A, Zahri S. Helicobacter pylori babA2 Positivity Predicts Risk of Gastric Cancer in Ardabil, a Very High-Risk Area in Iran. Asian Pac J Cancer Prev 2016; 17:733-8. [DOI: 10.7314/apjcp.2016.17.2.733] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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9
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Wang YK, Kuo FC, Liu CJ, Wu MC, Shih HY, Wang SSW, Wu JY, Kuo CH, Huang YK, Wu DC. Diagnosis of Helicobacter pylori infection: Current options and developments. World J Gastroenterol 2015; 21:11221-11235. [PMID: 26523098 PMCID: PMC4616200 DOI: 10.3748/wjg.v21.i40.11221] [Citation(s) in RCA: 232] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 08/06/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.
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