Several infectious agents are considered to be causes of cancer in humans. The fraction of the different types of cancer, and of all cancers worldwide and in different regions, has been estimated using several methods; primarily by reviewing the evidence for the strength of the association (relative risk) and the prevalence of infection in different world areas. The estimated total of infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of the global cancer burden. The principal agents are the bacterium Helicobacter pylori (5.5% of all cancer), the human papilloma viruses (5.2%), the hepatitis B and C viruses (4.9%), Epstein-Barr virus (1%), human immunodeficiency virus (HIV) together with the human herpes virus 8 (0.9%). Relatively less important causes of cancer are the schistosomes (0.1%), human T-cell lymphotropic virus type I (0.03%) and the liver flukes (0.02%). There would be 26.3% fewer cancers in developing countries (1.5 million cases per year) and 7.7% in developed countries (390,000 cases) if these infectious diseases were prevented. The attributable fraction at the specific sites varies from 100% of cervix cancers attributable to the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide) caused by liver flukes.

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The global health burden of infection-associated cancers in the year 2002.

Background: Guidelines on the management of Helicobacter pylori , which cover indications for management and treatment strategies, were produced in 2000. Aims: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer. Results: Eradication of H pylori infection is recommended in ( a ) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; ( b ) patients with atrophic gastritis; ( c ) first degree relatives of patients with gastric cancer; ( d ) patients with unexplained iron deficiency anaemia; and ( e ) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a “test and treat” strategy if other causes are excluded. Eradication of H pylori infection ( a ) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and ( b ) may prevent peptic ulcer in patients who are naive users of non-steroidal anti-inflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility. Conclusion: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development.

https://gut.bmj.com/content/gutjnl/56/6/772.full.pdf

Current concepts in the management of Helicobacter pylori infection - The Maastricht III Consensus Report

Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.

Pathogenesis of Helicobacter pylori Infection

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

https://gut.bmj.com/content/gutjnl/66/1/6.full.pdf

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Management of Helicobacter pylori infection is evolving and in this 4th edition of the Maastricht consensus report aspects related to the clinical role of H pylori were looked at again in 2010. In the 4th Maastricht/Florence Consensus Conference 44 experts from 24 countries took active part and examined key clinical aspects in three subdivided workshops: (1) Indications and contraindications for diagnosis and treatment, focusing on dyspepsia, non-steroidal anti-inflammatory drugs or aspirin use, gastro-oesophageal reflux disease and extraintestinal manifestations of the infection. (2) Diagnostic tests and treatment of infection. (3) Prevention of gastric cancer and other complications. The results of the individual workshops were submitted to a final consensus voting to all participants. Recommendations are provided on the basis of the best current evidence and plausibility to guide doctors involved in the management of this infection associated with various clinical conditions.

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Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report

ContextAlthough chronic Helicobacter pylori infection
is associated with gastric cancer, the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers
is unknown.ObjectiveTo determine whether treatment of H pylori infection
reduces the incidence of gastric cancer.Design, Setting, and ParticipantsProspective, randomized, placebo-controlled, population-based primary
prevention study of 1630 healthy carriers of H pylori infection
from Fujian Province, China, recruited in July 1994 and followed up until
January 2002. A total of 988 participants did not have precancerous lesions
(gastric atrophy, intestinal metaplasia, or gastric dysplasia) on study entry.InterventionPatients were randomly assigned to receive H pylori eradication treatment: a 2-week course of omeprazole, 20 mg, a combination
product of amoxicillin and clavulanate potassium, 750 mg, and metronidazole,
400 mg, all twice daily (n = 817); or placebo (n = 813).Main Outcome MeasuresThe primary outcome measure was incidence of gastric cancer during follow-up,
compared between H pylori eradication and placebo
groups. The secondary outcome measure was incidence of gastric cancer in patients
with or without precancerous lesions, compared between the 2 groups.ResultsAmong the 18 new cases of gastric cancers that developed, no overall
reduction was observed in participants who received H pylori eradication treatment (n = 7) compared with those who did not (n =
11) (P = .33). In a subgroup of patients with no
precancerous lesions on presentation, no patient developed gastric cancer
during a follow-up of 7.5 years after H pylori eradication
treatment compared with those who received placebo (0 vs 6; P = .02). Smoking (hazard ratio [HR], 6.2; 95% confidence interval
[CI], 2.3-16.5; P<.001) and older age (HR, 1.10;
95% CI, 1.05-1.15; P<.001) were independent risk
factors for the development of gastric cancer in this cohort.ConclusionsWe found that the incidence of gastric cancer development at the population
level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period
of 7.5 years in a high-risk region of China. In the subgroup of H pylori carriers without precancerous lesions, eradication of H pylori significantly decreased the development of gastric
cancer. Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted.

https://jamanetwork.com/journals/jama/articlepdf/197985/JOC30303.pdf

Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial.

Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study.

AIM: To determine the prevalence of antralization at the edge of proximal gastric ulcers, and the effect of H. pylori eradication on the mucosal appearances.

METHODS: Biopsies were taken from the antrum, body and the ulcer edge of patients with benign proximal gastric ulcers before and one year after treatment. Gastric mucosa was classified as antral, transitional or body type. H. pylori positive patients received either triple therapy, or omeprazole.

RESULTS: Patients with index ulcers in the incisura, body or fundus (n = 116) were analyzed. Antral-type mucosa was more prevalent at the ulcer edge in H. pylori-positive patients than H. pylori-negative patients (93% vs 60%, OR = 8.95, 95%CI: 2.47-32.4, P = 0.001). At one year, there was a significant reduction in the prevalence of antralization (from 93% to 61%, P = 0.004) at the ulcer edge in patients with H. pylori being eradicated. However, there was no difference in the prevalence of antralization at the ulcer edge in those with persistent infection.

CONCLUSION: H. pylori infection is associated with antralization at the edge of proximal gastric ulcers, which may be reversible in some patients after eradication of the infection.

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Wayne Hsing Cheng Hu

Papers

Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial.

Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study.

Antralization at the edge of proximal gastric ulcers: does Helicobacter pylori infection play a role?