Helicobacter pylori

In brief

What it is, and how it survives the stomach

Helicobacter pylori is a bacterium: a single-celled organism, far smaller and simpler than the worms and flukes elsewhere in this Atlas, and the only one of this season's confirmed carcinogens that is not an animal. It is Gram-negative, meaning that in the stain microbiologists use to sort bacteria its thin cell wall takes the pink counter-stain rather than the purple, and it is shaped like a short corkscrew a few micrometers long, a micrometer being a thousandth of a millimeter ². Its first genome, published in 1997, was a single circular chromosome of 1,667,867 base pairs carrying 1,590 predicted genes, with well-developed machinery for movement and for scavenging iron ⁴.

Its home is the one organ built to be nearly sterile. The stomach bathes its contents in acid strong enough to kill most swallowed microbes, and for most of the twentieth century that was the reason no one believed bacteria could live there ¹⁸. H. pylori lives there by two tricks. It makes large amounts of urease, an enzyme that splits urea — a small waste molecule present in the stomach — into ammonia, which neutralizes the acid in the thin layer of fluid around each cell; and it drives itself with a tuft of whip-like flagella down out of the acid and into the mucus gel that lines the stomach wall, where the acid is buffered ^3,4. The genome paper noted that the organism's survival in acid depends in part on its ability to hold a positive electrical charge on the inside of its membrane at low pH ⁴.

Urease is not a convenience but a requirement. When researchers fed gnotobiotic (germ-free) piglets a mutant strain whose urease had been crippled to 0.4% of normal activity by chemical mutagenesis, the mutant colonized none of ten animals, while the ordinary strain colonized all seven, and only the ordinary strain produced gastritis ¹⁷. The ammonia the enzyme makes is also what two of the common diagnostic tests look for, as later sections describe.

The infection is usually caught in early childhood, passed person to person within families by the mouth, and once established it persists for life unless it is treated ³. More than half the world's people carry it. A 2017 meta-analysis of 184 studies from 62 countries estimated about 4.4 billion infected in 2015, with the pooled prevalence highest in Africa at 70.1% (95% confidence interval 62.6 to 77.7) and lowest in Oceania at 24.4%, ranging among individual countries from 18.9% in Switzerland to 87.7% in Nigeria ⁵. A confidence interval is the range within which the true value probably lies given the size of the studies. The share is falling where sanitation and eradication improve: a 2023 meta-analysis of 224 studies estimated that global prevalence dropped from 58.2% in 1980–1990 to 43.1% in 2011–2022, the decline sharpest after 2011 and largest in the World Health Organization (WHO) African region, though the heterogeneity between studies was very high ⁶.

The reversal: from stress and acid to a bacterium

For most of the twentieth century, peptic ulcers — raw sores in the lining of the stomach or the first part of the small intestine — were taught to be caused by stress and stomach acid, and treated by suppressing acid; the idea that a bacterium lived in the acid stomach was dismissed ^13,18. The reversal is the reason this page exists, because it is the clean precedent for everything the season asks about the parasites: an infectious cause hidden in plain sight, resisted for years, and finally proven. Spiral organisms in the stomach were not, in fact, new to science when Warren and Marshall began: the Italian pathologist Giulio Bizzozero had described a closely related Helicobacter in the canine stomach roughly a hundred years earlier, and comparable sightings in animals and people were made and forgotten repeatedly across the following decades, so the bacterium was almost literally hidden in plain sight long before anyone proved what it did ²⁷.

In 1983 two letters in The Lancet, from the pathologist J. Robin Warren and the physician Barry Marshall in Perth, Western Australia, reported curved bacteria sitting on the stomach lining of patients with chronic gastritis ¹. In 1984 they published the full study: antral (from the antrum, the lower stomach) biopsies from 100 consecutive patients showed spiral or curved bacilli in 58, they cultured the organism from 11, found it to be Gram-negative, flagellate and related to the genus Campylobacter, and noted it was present in almost every patient with active chronic gastritis, duodenal ulcer or gastric ulcer ². That was an association, and the medical world's skepticism turned on exactly that point: the bacteria might be passengers on already-damaged tissue rather than its cause.

Marshall answered the objection on himself. In 1985 he and colleagues reported that a volunteer with a histologically normal stomach — Marshall — had swallowed a culture of the organism, developed a short illness, and had histologically proven gastritis on the tenth day that had largely resolved by the fourteenth ¹⁸. One self-experiment cannot prove that the bacterium causes ulcers or cancer, and it did not; what it showed was that the organism could take a healthy stomach and inflame it, which broke the passenger argument. Over the next decade the bacterium was renamed Helicobacter pylori, its genome was sequenced, its link to cancer was measured, and in 2005 Warren and Marshall were awarded the Nobel Prize in Physiology or Medicine for the discovery that peptic ulcer disease is caused by infection with H. pylori ^4,12,13.

The lesson the season takes from it is narrow and exact. A bacterium was living where no bacterium was thought to live, causing a disease blamed on something else, and the proof required culturing it, giving it to a host, and watching the disease appear — a version of Koch's postulates, the classic checklist for showing a microbe causes a disease ¹⁸. The parasites this season asks about are harder on every count, as the final section sets out, but the shape of the question is the one Warren and Marshall answered.

What it does to you: gastritis, ulcer, cancer, lymphoma

In almost everyone it infects, H. pylori produces chronic gastritis, a lasting inflammation of the stomach lining, and in most people that is all it ever does: the infection is silent and causes nothing a patient would notice ³. The diseases that matter grow out of that inflammation in a minority, over years to decades.

The first is peptic ulcer disease, the sores in the stomach or duodenum that the bacterium was discovered through; it is the cause of most such ulcers that are not due to anti-inflammatory painkillers, and eradicating it heals them and stops them returning ^2,3. The second, and the reason the organism is in a cancer season, is gastric adenocarcinoma, cancer of the glandular lining of the stomach. The link was first measured in 1991: a nested case-control study drawn from a cohort of 128,992 people, using blood stored since the 1960s, found that 84% of 109 confirmed non-cardia gastric adenocarcinomas had been infected beforehand, against 61% of matched controls, an odds ratio of 3.6 (95% confidence interval 1.8 to 7.3); tumors at the junction with the esophagus were not linked ²⁸. An odds ratio compares the odds of prior infection in cases and controls; 3.6 means roughly three and a half times the odds.

The strongest human evidence that the infection comes first is a prospective study. Uemura and colleagues followed 1,526 Japanese patients for a mean of 7.8 years: gastric cancer developed in 36 (2.9%) of the 1,246 who were infected and in none of the 280 who were not, and within the infected group the risk was concentrated in those who already had severe atrophy, corpus-predominant gastritis or intestinal metaplasia ⁷. These patients were referred for endoscopy rather than drawn at random, so the percentages describe that population, not the general public, but the contrast — cancer only in the infected — is the point.

The third disease is the one that makes the season's case most sharply: gastric MALT lymphoma, a cancer of the immune tissue (mucosa-associated lymphoid tissue) that H. pylori provokes in the stomach wall. About 90% of gastric MALT lymphomas are related to the infection ¹⁹. In 1993 Wotherspoon and colleagues treated 6 patients who had low-grade gastric MALT lymphoma and H. pylori with antibiotics; the bacterium was eradicated in all, and on repeat biopsy the lymphoma had disappeared in 5 ⁸. A cancer that regresses when an antibiotic clears the organism driving it is a rare and powerful thing, and it is examined again in the prevention section. Not every case obliges: tumors carrying the chromosomal translocation t(11;18), which fuses two genes into a protein that switches on the inflammatory regulator NF-κB, are more often H. pylori-negative and do not respond to eradication ¹⁹.

Why most infected people never get any of this is itself a live question. Only a small fraction of colonized people develop gastric cancer, and the risk is shaped by the strain's genotype and the host's — chiefly how fierce an inflammatory response the pair produces — which is why the same bacterium is nearly harmless in one person and carcinogenic in another ^7,26.

The classification: Group 1 since 1994

In 1994 the International Agency for Research on Cancer — the World Health Organization's cancer agency, in Lyon, France — convened a Working Group that met from 7 to 14 June and produced Monographs Volume 61, 241 pages, titled 'Schistosomes, liver flukes and Helicobacter pylori' ¹⁰. That is the point the season keeps returning to: the stomach bacterium was evaluated in the same volume, by the same kind of panel, as the blood fluke and the liver flukes that this Atlas covers elsewhere. The resulting classification put H. pylori in Group 1, the category for agents with sufficient evidence of causing cancer in humans — a statement about how certain the causal link is, not about how large the risk is in any one person.

A word on sourcing. The PubMed record for Volume 61 carries no abstract, so the Group 1 assignment itself is not quotable from that record; it is taken from the peer-reviewed literature that restates it, including IARC's own current burden analysis, which lists H. pylori among exactly 12 Group 1 infectious agents ^9,10. The classification was not a one-time call: in 2012 IARC published Volume 100B, a deliberate re-review of the agents already in Group 1, and H. pylori was examined again and kept there, alongside S. haematobium and the liver flukes ¹¹.

Group 1 is a hazard classification, which asks only whether an agent can cause cancer, not how much. For H. pylori the 'how much' turns out to be very large, which is the subject of the next section, and unlike most Group 1 agents it is one that can be found with a cheap test and removed with antibiotics. The current ratings for all the Group 1 biological agents, this one included, are kept on IARC's public Monographs pages and in the agency's periodic burden analyses ^9,11.

The burden: the largest infectious cause of cancer

IARC counts, every few years, how many of the world's cancers can be attributed to infection, and in every edition H. pylori has led the list. The current analysis, using 2024 incidence data, attributes 2.3 million new cancers — 12% of all cancer worldwide — to the 12 Group 1 infectious agents, and of those H. pylori accounts for about 760,000 (a population-attributable fraction of 4%), more than any other single agent and just ahead of human papillomavirus at 750,000 ⁹. A population-attributable fraction is the share of cases that would not have happened without the exposure. The burden is concentrated: eastern Asia alone carried 990,000 of the 2.3 million infection-attributable cancers, 42% of the world total ⁹.

The figure has been stable and is easing slightly as infection recedes. The previous editions attributed to H. pylori about 810,000 cancers in 2018, 770,000 in 2012, and — in the founding paper of the series — a leading share of roughly 2 million infection-attributable cancers in 2008, when H. pylori, the hepatitis B and C viruses and human papillomavirus together accounted for 1.9 million ^32,33,34. Reading the series in order, the H. pylori count drifts down from 810,000 to 760,000 even as the world's population grows, which is what a falling prevalence does to a cancer count. These analyses are produced by IARC, the same agency that issues the Group 1 classifications being counted, a point worth naming even though the arithmetic is standard ⁹.

The cancer behind most of that number is gastric adenocarcinoma, which is itself one of the world's major cancers. A separate IARC modeling study estimated about 1.1 million new gastric cancers and 770,000 deaths in 2020, highest in eastern Asia, and projected the annual burden to rise to about 1.8 million cases and 1.3 million deaths by 2040 on current demographic trends, naming eradication of H. pylori as the key route to primary prevention ³⁵. That projection is the argument for treating the infection as a public-health target rather than a private nuisance: a single, findable, treatable organism sits behind a seven-figure cancer burden. A 2025 IARC analysis reframed the same problem across a lifetime: of about 15.6 million lifetime gastric cancers expected (95% uncertainty interval 14.0 to 17.3 million) in the people born between 2008 and 2017 across 185 countries, 76% were attributable to H. pylori, two-thirds of the cases fell in Asia, and 42% were expected in historically lower-incidence regions as populations change — with the future burden in sub-Saharan Africa possibly six times its 2022 level, which is why the IARC authors, like Morgan's group, call for population-wide H. pylori screen-and-treat ³⁶.

Set against the parasites this season is really about, the scale is the first thing that stands out. In the same 2024 analysis, the three Group 1 parasites together account for fewer than 10,000 cancers — about 5,900 bladder cancers from the blood fluke and about 3,800 intrahepatic bile-duct cancers (cholangiocarcinomas) from the two liver flukes — against H. pylori's 760,000 ⁹. The bacterium is not a better-studied version of the fluke problem; it is a vastly larger one that happens to be easier to solve.

How it causes cancer: CagA, VacA and chronic inflammation

The bacterium does not sit inside the cells it transforms; it sits in the mucus above them and acts on them from there, through secreted toxins and a decades-long inflammation. The honest frame, from the field's own reviews, is that infection is necessary but nowhere near sufficient: only a small fraction of infected people develop cancer, and strain and host genotype decide which ²⁶.

The sharpest-studied factor is CagA. The most virulent strains carry the cag pathogenicity island, a block of about 40,000 base pairs of DNA, present only in the disease-associated 'type I' strains, that assembles a molecular syringe (a type IV secretion system) and injects the CagA protein directly into the stomach lining cells ^21,22. Once inside, CagA is tagged with phosphate at repeated sequence motifs called EPIYA segments and latches onto SHP-2, a human signaling protein that behaves as an oncoprotein when deregulated ^21,23. That this is not merely correlation was shown in animals: mice engineered to make CagA throughout the body or in the stomach developed gastric epithelial overgrowth and, in some, adenocarcinomas of the stomach and small intestine, along with leukemias and B-cell lymphomas, while mice making a phosphorylation-resistant CagA stayed healthy — the first direct evidence that a bacterial protein can act as an oncoprotein in a mammal ²². This is animal evidence from engineered mice, not from natural infection, and it is strong for exactly that reason and limited for exactly that reason.

CagA's form varies by geography in a way that tracks the cancer. Western strains carry an EPIYA-C segment that binds SHP-2 weakly; East Asian strains carry an EPIYA-D segment that binds it strongly, and mice making East Asian CagA developed more tumors than mice making the Western form — a mechanistic correlate, in mice, of why gastric cancer is commoner in East Asia ³⁷. It is a correlate, not a measurement in people.

A second toxin, VacA, the vacuolating cytotoxin, is made by almost all strains; it drives cells to form large vacuoles and die by apoptosis (programmed cell death), helps the bacterium persist, and may work together with CagA ²⁴. Around both, the cag island provokes the lining to secrete interleukin-8, a signal that recruits inflammatory white cells, so the infection maintains a chronic inflammation — one of the recognized general routes to cancer — for decades, generating the oxygen and nitrogen radicals that damage DNA ^21,25.

The inflammation and the damage climb a defined staircase, the Correa cascade, named for the pathologist Pelayo Correa, who assembled it from pathology and epidemiology in 1992: chronic gastritis, then atrophy (loss of the glands), then intestinal metaplasia (the lining turning intestine-like), then dysplasia, then carcinoma, with H. pylori and dietary salt driving the early steps and nitrosating chemicals (nitrogen compounds that can chemically damage DNA) proposed as the carcinogens that finish the job ²⁰. The model was built from pathology and epidemiology, including the early prospective case-control studies, assembled in a 1994 review, that showed infection precedes the adenocarcinoma rather than merely accompanying it ^20,38. The prospective Japanese data map onto it: cancer arose overwhelmingly in patients who had already reached severe atrophy or intestinal metaplasia ⁷.

A final wrinkle explains why the risk is set by duration rather than by the bug being present at the end. CagA appears to start the process rather than sustain it: once enough genetic changes, and epigenetic ones — shifts in gene activity that leave the DNA letters unchanged — have accumulated, the cancer no longer needs the bacterium, so the carcinogenesis is described as 'hit-and-run' ²³. That is why decades of silent infection, not the organism caught red-handed in the tumor, is what the risk tracks — a point that matters directly to the parasite question, where the worm may be long gone by the time the cancer appears.

Finding it and killing it, against rising resistance

Because the organism is easy to detect and, in principle, easy to remove, the clinical strategy is 'test and treat': find the infection, give a short course of drugs, then confirm it is gone. It can be found without an endoscopy by a urea breath test — the patient swallows urea labeled with a carbon isotope and the bacterium's urease releases labeled carbon dioxide into the breath — or by a stool antigen test, or by serology for antibodies in blood; or it can be found at endoscopy, where a biopsy is examined under the microscope, tested for urease on the spot, or cultured ³. The 2015 Kyoto global consensus went further and recommended reclassifying gastritis by its cause and, where feasible, eradicating H. pylori before the precancerous changes of the Correa cascade set in ³⁹. In the United States, where gastric cancer is uncommon overall but concentrated in identifiable groups, a 2025 American Gastroenterological Association (AGA) practice update set out a targeted version of the same idea: H. pylori eradication as primary prevention, and endoscopic screening and surveillance of precancerous changes such as gastric intestinal metaplasia as secondary prevention, aimed at higher-risk people — first-generation immigrants from high-incidence regions and those with a first-degree relative who had gastric cancer ⁴⁰.

Treatment is a strong acid-suppressing drug combined with two antibiotics, or with bismuth and antibiotics, for one to two weeks ^3,15. The problem is that the antibiotics are losing their edge. A 2018 meta-analysis of 178 studies and 66,142 isolates from 65 countries found resistance to clarithromycin, metronidazole and levofloxacin at or above 15% in most WHO regions and rising, and showed that clarithromycin resistance made failure of a clarithromycin-based regimen almost seven times as likely (odds ratio 6.97, 95% confidence interval 5.23 to 9.28) ⁴¹. In 2017 the World Health Organization placed clarithromycin-resistant H. pylori in the high-priority tier of its list of antibiotic-resistant bacteria in need of new drugs ³⁰.

The guidelines have been rewritten around that resistance. The 2022 Maastricht VI/Florence consensus, 41 experts from 29 countries, recorded that H. pylori infection is now formally an infectious disease in the ICD-11 — which in principle means every infected patient should be offered treatment — and called for susceptibility testing and careful choice of first-line and rescue regimens ¹⁵. The 2024 American College of Gastroenterology guideline made bismuth quadruple therapy for 14 days the preferred first-line treatment when the strain's susceptibility is unknown, with rifabutin-based or acid-blocker dual therapy as alternatives, and insisted that clarithromycin- or levofloxacin-based salvage regimens be used only when susceptibility is confirmed and that every patient have a test of cure afterward ¹⁴. The reason the test of cure matters is that resistance has made failure common enough that you can no longer assume a course worked. A parallel shift concerns the acid-suppressing drug itself: a 2024 AGA update advised that the newer potassium-competitive acid blockers (P-CABs, such as vonoprazan), which block acid production faster and more potently, should take the place of the older proton-pump inhibitors — the long-standard acid-suppressing drugs — in eradication regimens for most patients ⁴².

This is the first way the H. pylori precedent is more forgiving than the parasite problem: the organism gives itself away through its own urease in a breath test, and a two-week course of common drugs clears most infections. The caveat, growing each year, is that 'most' is shrinking as resistance rises ^14,41.

• Urea breath testThe patient swallows urea labeled with a carbon isotope; the bacterium's urease splits it, and the labeled carbon dioxide turns up in the breath — a non-invasive test that detects an active infection ³.A standard non-invasive test both to diagnose the infection and, afterward, to confirm it has been cured ^3,14Endorsed across current guidelines as a first-line non-invasive test and as the post-treatment test of cure ^14,15It shows the bacterium is present, not which antibiotics will kill it; resistance needs culture or molecular testing ^15,41
• Stool antigen testDetects bacterial proteins shed in the feces, another non-invasive way to find an active infection ³.Diagnosis and confirmation of cure, including where a breath test is not available ^3,14Accepted in guidelines as a non-invasive diagnostic and test of cure ¹⁴Like the breath test, it cannot report which drugs the strain resists ⁴¹
• Endoscopic biopsy (histology, rapid urease test, culture)At endoscopy a fragment of stomach lining is examined under the microscope for the bacterium and its inflammation, tested on the spot for urease, or grown in culture ^2,3.The way to stage the damage along the Correa cascade and to grow the organism for antibiotic susceptibility testing ^20,41The only approach that both stages the mucosal damage and, through culture, measures which drugs still work ^15,41It requires an endoscopy, so it is not used for simple screening, and culture is demanding and not available everywhere ^14,15
• Serology (antibody test)Detects antibodies the body has made against the bacterium in blood; Parsonnet's 1991 study read H. pylori IgG antibodies in serum stored since the 1960s ²⁸.Epidemiology and research, including the large studies that estimate how many people are infected ^5,28Good for measuring exposure across a population, which is how global prevalence is estimated ^5,6It reflects past or present exposure rather than a confirmed live infection, so guidelines rely on breath or stool tests to confirm cure ¹⁴

Killing it can prevent, and even reverse, the cancer

The feature that sets H. pylori apart from almost every other carcinogen is that removing it has been shown, in randomized trials, to lower the cancer it causes — and in one cancer to reverse it. This is the part of the story the season most wants to hold up against the parasites, because it is the proof that an infectious cause of cancer, once identified, can be acted on.

The reversal is the MALT lymphoma. Wotherspoon's 1993 report of 6 patients whose low-grade gastric MALT lymphoma disappeared in 5 after antibiotics cleared H. pylori has been borne out: eradication is now first-line treatment for early H. pylori-associated gastric MALT lymphoma, and a large share respond, the exceptions being tumors with the t(11;18) translocation ^8,19. A cancer that regresses when you kill the bacterium behind it is close to unique.

For gastric adenocarcinoma the effect is prevention rather than reversal, and it has been measured in three kinds of trial. In patients who had already had an early gastric cancer removed, eradication cut the rate of a new (metachronous) cancer: an open-label trial of 544 patients found 9 new cancers in the treated group versus 24 in controls at 3 years (odds ratio 0.353, 95% confidence interval 0.161 to 0.775), and a later double-blind trial of 470 patients found a hazard ratio of 0.50 (0.26 to 0.94) and, strikingly, that gastric-body atrophy improved in 48.4% of the treated versus 15.0% of controls — the Correa cascade partly running backwards ^29,43. In people at high risk because a first-degree relative had gastric cancer, a double-blind trial of 1,676 relatives found that eradication cut gastric cancer over a median 9.2 years (hazard ratio 0.45, 0.21 to 0.94), and the effect was larger still in those actually cleared of the infection (0.8% versus 2.9% with persistent infection) ³¹.

In the general population the evidence is a Cochrane meta-analysis of 7 randomized trials and 8,323 healthy, asymptomatic infected adults: searching for and eradicating H. pylori reduced gastric-cancer incidence (risk ratio 0.54, 95% confidence interval 0.40 to 0.72) and death from gastric cancer (0.61, 0.40 to 0.92), at moderate certainty ¹⁶. The caveat the authors insist on is that six of the seven trials were in Asian populations, where gastric cancer is common, so the benefit cannot simply be assumed in low-incidence countries ¹⁶. Still, the direction is settled: across prevention trials, removing the carcinogen lowers the cancer.

That is the whole appeal of the precedent. For H. pylori the chain runs clean — find it, kill it, and the cancer falls — in a way that has not been demonstrated for any of the parasites, where no trial has yet shown that treating the infection lowers the cancer it is linked to.

Why it is the right analogy, and where it breaks

H. pylori is the season's load-bearing precedent because its story is the one the parasite question is reaching for: an infectious agent, long dismissed, shown to cause a human cancer, placed in IARC Group 1, and — crucially — counted in the millions and acted on. If a bacterium could make that journey against decades of certainty that ulcers were about stress and acid, then the possibility that a worm causes more cancer than anyone counts is not absurd on its face ^9,10,18.

It is the right analogy in three specific ways. First, it was resisted for the same reason: the organism was found alongside the disease, and critics said it was a passenger, exactly the charge leveled at parasites found in tumors ^2,18. Second, it sits in the very same IARC volume as the blood fluke and liver flukes, Volume 61 of 1994, evaluated by the same machinery ¹⁰. Third, it proves the end state the season is testing for — that an infection can cause a common cancer and that removing it can prevent that cancer ^8,16.

But the analogy breaks in ways that matter, and the honest version of the argument needs them. A bacterium is easy to find: it betrays itself through its own urease in a breath test, and it is small enough to be caught by non-invasive tests done at scale ³. A worm is not: it may be gone from the body by the time the cancer appears, leaving nothing to detect, which is the recurring theme of the parasite pages. A bacterium is also easy to kill — a week or two of common antibiotics — whereas the flukes require specific antiparasitic drugs and reinfection is routine where they are endemic. And the cleanest part of the H. pylori story, the regression of MALT lymphoma when the organism is cleared, has no counterpart in the fluke cancers: there is no trial showing that treating schistosomiasis or liver-fluke infection makes the associated bladder or bile-duct cancer regress or even fall ^8,9.

There is one more asymmetry that cuts against treating H. pylori as a simple villain, and it is worth stating because it keeps the account honest. The same bacterium that causes stomach cancer is inversely associated with cancer of the esophagus: a meta-analysis of 19 studies found H. pylori, and specifically its CagA-positive strains, associated with roughly half the risk of esophageal adenocarcinoma (summary odds ratio 0.56, 95% confidence interval 0.46 to 0.68; CagA-positive 0.41, 0.28 to 0.62), and its authors suggested that the decline of the organism may be part of why that cancer has risen in the West ⁴⁴. So the precedent is not 'a germ causes cancer, remove the germ'; it is subtler — an ancient inhabitant of the human stomach that drives one cancer while guarding against another, proven to cause the first and worth removing for it, but not a pure pathogen. That nuance is the adult version of the lesson the parasite question should take from it.

What was believed and is not, and what is still unknown

What changed. The belief that ulcers were caused by stress and acid, and that no bacterium could live in the stomach, was overturned by Warren and Marshall's cultures, by Marshall's self-experiment, and by the prospective and trial evidence that followed; the discovery earned the 2005 Nobel Prize ^7,12,18. The belief that a cancer could not be cured by an antibiotic was overturned, in one cancer, by the regression of gastric MALT lymphoma after eradication ⁸. And the belief that the carcinogenic organism must be present in the tumor was complicated by the 'hit-and-run' finding that CagA can start the process and then be dispensable ²³.

How much cancer it causes, and where. The 760,000 figure for 2024 is an attributable estimate built on prevalence and relative-risk data, produced by IARC, and it drifts as prevalence falls; it is a careful model, not a tally of tumors sequenced for the organism ^9,32. The burden is overwhelmingly in eastern Asia and in lower-income regions today, but it is projected to shift: on the IARC lifetime estimate a rising share of future gastric cancers will fall in historically lower-incidence areas, sub-Saharan Africa most of all, where the burden could run to several times its current level ³⁶. Whether population-wide screen-and-treat should be adopted outside the high-incidence Asian settings where the trials were done is unsettled, because the Cochrane evidence cannot simply be extrapolated ^16,35; the most recent US expert guidance answers the question only for identifiable high-risk groups rather than for the whole population ⁴⁰.

Why most infected people never get cancer. Only a small fraction of the billions infected develop gastric cancer, and although strain genotype (such as the cag island and the East Asian form of CagA) and host inflammatory genotype are known to shift the risk, the full set of factors that decides who progresses up the Correa cascade and who does not is not settled ^7,26,37. Nor is it known how far the atrophy that eradication reverses translates, in every setting, into cancers actually prevented ⁴³.

The double-edged organism. H. pylori has lived in human stomachs for the whole of recorded history and is now disappearing from them, and it both causes stomach cancer and appears to protect against esophageal adenocarcinoma; what the loss of the organism will do to the overall balance of these cancers, and whether eradicating it in people at low gastric-cancer risk does more good than harm, is an open question the inverse-association data raise but cannot answer ^6,44. For the season's purpose the settled part is enough: a once-dismissed infection is the largest known infectious cause of human cancer, found with a breath and killed with a pill — the proof of concept against which the harder, quieter parasite question is measured ^8,9.

Where it connects

Sources

44 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1. 1
   Warren JR, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis.Lancet · 1983 · 1(8336):1273-5PMID 6134060

   The two 1983 Lancet letters by Warren and by Marshall that first reported spiral bacteria on the gastric lining in chronic gastritis. The PubMed record carries no abstract, so the detail comes from the 1984 paper and later reviews; this is the dated primary record of the first report.

2. 2
   Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.Lancet · 1984 · 1(8390):1311-5doi:10.1016/s0140-6736(84)91816-6 · PMID 6145023

   The foundational paper: antral biopsies from 100 consecutive patients, spiral bacilli in 58, cultured from 11, Gram-negative, flagellate, microaerophilic, 'a new species related to the genus Campylobacter,' present in almost all patients with active chronic gastritis, duodenal ulcer or gastric ulcer. Association, not yet proof of cause.

3. 3
   Malfertheiner P, Camargo MC, El-Omar E, Liou JM, Peek R, Schulz C, Smith SI, Suerbaum S. Helicobacter pylori infection.Nat Rev Dis Primers · 2023 · 9(1):19doi:10.1038/s41572-023-00431-8 · PMID 37081005

   Authoritative current review: H. pylori causes chronic gastritis that can progress to peptic ulcer, gastric cancer and MALT lymphoma; is usually transmitted in childhood and persists for life if untreated; affects about half the world; colonizes gastric epithelium in an acidic environment; is diagnosed by endoscopic and non-invasive (breath, stool, serology) tests; treatment combines acid suppression with antibiotics and/or bismuth, and rising resistance demands susceptibility testing. A review, not new data.

4. 4
   Tomb JF, White O, Kerlavage AR, et al. The complete genome sequence of the gastric pathogen Helicobacter pylori.Nature · 1997 · 388(6642):539-47doi:10.1038/41483 · PMID 9252185

   First genome of the organism (strain 26695): a circular chromosome of 1,667,867 base pairs and 1,590 predicted coding sequences, with systems for motility and iron scavenging, and acid survival depending in part on establishing a positive inside-membrane potential at low pH. A single reference strain.

5. 5
   Hooi JKY, Lai WY, Ng WK, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis.Gastroenterology · 2017 · 153(2):420-429doi:10.1053/j.gastro.2017.04.022 · PMID 28456631

   Pooled 184 studies from 62 countries: Africa highest at 70.1% (95% CI 62.6-77.7), Oceania lowest at 24.4%, Switzerland 18.9% and Nigeria 87.7%; about 4.4 billion people infected worldwide in 2015. A meta-analysis of heterogeneous studies; the global total is an extrapolation.

6. 6
   Li Y, Choi H, Leung K, Jiang F, Graham DY, Leung WK. Global prevalence of Helicobacter pylori infection between 1980 and 2022: a systematic review and meta-analysis.Lancet Gastroenterol Hepatol · 2023 · 8(6):553-564doi:10.1016/S2468-1253(23)00070-5 · PMID 37086739

   224 studies, ~2.98 million people: estimated global prevalence fell from 58.2% (95% CI 50.7-65.8) in 1980-90 to 43.1% (40.3-45.9) in 2011-22, static in between and declining sharply after 2011, largest decline in the WHO African region. Heterogeneity was very high (I² 99.9%); a meta-analysis, not a count.

7. 7
   Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer.N Engl J Med · 2001 · 345(11):784-9doi:10.1056/NEJMoa001999 · PMID 11556297

   Prospective study of 1,526 Japanese patients, mean follow-up 7.8 years: gastric cancer developed in 36 (2.9%) of 1,246 infected patients and in none of 280 uninfected; risk was higher with severe atrophy, corpus-predominant gastritis and intestinal metaplasia. Human cohort; patients were referred for endoscopy, not a general population.

8. 8
   Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori.Lancet · 1993 · 342(8871):575-7doi:10.1016/0140-6736(93)91409-f · PMID 8102719

   Six patients with low-grade gastric MALT lymphoma and H. pylori were given antibiotics; the bacterium was eradicated in all, and the lymphoma vanished on repeat biopsy in 5. The first demonstration that killing the bacterium can regress a cancer. Six patients, short follow-up.

9. 9
   Rumgay H, Georges D, Huang Y, et al. Global burden of cancer attributable to infections in 2024: a worldwide incidence analysis.Lancet Oncol · 2026 · 27(10):1237-1248doi:10.1016/S1470-2045(26)00307-4 · PMID 42805198

   IARC's current accounting: 12 Group 1 infectious agents (H. pylori, HPV, HBV, HCV, EBV, KSHV, S. haematobium, HTLV-1, O. viverrini, C. sinensis, Merkel cell polyomavirus, HIV) caused 2.3 million cancers in 2024, 12% of all cancer; H. pylori was the largest single cause at 760,000 (population-attributable fraction 4%), ahead of HPV at 750,000, with eastern Asia holding 990,000 (42%). The authors declare no competing interests; they are IARC/WHO staff, the same agency that issues the Group 1 classifications being counted.

10. 10
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Schistosomes, liver flukes and Helicobacter pylori.IARC Monogr Eval Carcinog Risks Hum · 1994 · 61:1-241PMID 7715068

    IARC Monographs Volume 61, the 1994 evaluation that classified H. pylori as carcinogenic to humans (Group 1) in the same 241-page volume as the schistosomes and liver flukes; the Working Group met in Lyon 7-14 June 1994. The PubMed record has no abstract, so the Group 1 assignment itself is taken from peer-reviewed papers that restate it; this record fixes the volume, scope and date.

11. 11
    IARC. Biological agents. Volume 100 B. A review of human carcinogens.IARC Monogr Eval Carcinog Risks Hum · 2012 · 100(Pt B):1-441PMID 23189750

    IARC Monographs Volume 100B (2012), the re-review of agents already in Group 1, including H. pylori alongside the liver flukes and S. haematobium. The record has no abstract; it documents that the classification was re-examined and upheld, with the wording taken from the volume itself.

12. 12
    Hellström PM. Spotlight on gastroenterology - the Nobel Prize Laureates in Physiology or Medicine 2005: John Robin Warren and Barry James Marshall.Scand J Gastroenterol · 2005 · 40(12):1383-5doi:10.1080/00365520500390402 · PMID 16293551

    An editorial marking the 2005 Nobel Prize in Physiology or Medicine awarded to Warren and Marshall. Secondary; the date and fact of the prize are the load-bearing points.

13. 13
    Zetterström R. The Nobel Prize in 2005 for the discovery of Helicobacter pylori: implications for child health.Acta Paediatr · 2006 · 95(1):3-5doi:10.1080/08035250500479616 · PMID 16373288

    Editorial: states the 2005 prize was for the discovery that peptic ulcer disease is caused by H. pylori infection, which affects about half the world's population and starts as an asymptomatic gastritis that can progress to ulcer. Secondary and framed for pediatrics.

14. 14
    Chey WD, Howden CW, Moss SF, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection.Am J Gastroenterol · 2024 · 119(9):1730-1753doi:10.14309/ajg.0000000000002968 · PMID 39626064

    The 2024 American College of Gastroenterology guideline: for treatment-naive patients, bismuth quadruple therapy for 14 days is preferred when antibiotic susceptibility is unknown, with rifabutin triple or potassium-competitive-acid-blocker dual therapy as alternatives; salvage regimens with clarithromycin or levofloxacin should be used only when susceptibility is confirmed, and every patient needs a post-treatment test of cure. A guideline for North America.

15. 15
    Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report.Gut · 2022 · 71(9):1724-1762doi:10.1136/gutjnl-2022-327745 · PMID 35944925

    The sixth Maastricht/Florence consensus, 41 experts from 29 countries: H. pylori infection is now recognized as an infectious disease in the ICD-11, which in principle means all infected patients should be offered treatment, and the continuing rise in antibiotic resistance calls for susceptibility testing and careful choice of first-line and rescue regimens. A consensus report.

16. 16
    Ford AC, Yuan Y, Forman D, Hunt R, Moayyedi P. Helicobacter pylori eradication for the prevention of gastric neoplasia.Cochrane Database Syst Rev · 2020 · 7(7):CD005583doi:10.1002/14651858.CD005583.pub3 · PMID 32628791

    Cochrane meta-analysis, 7 trials and 8,323 healthy asymptomatic infected adults: eradication reduced gastric-cancer incidence (risk ratio 0.54, 95% CI 0.40-0.72) and death from gastric cancer (0.61, 0.40-0.92), moderate-certainty evidence, six of seven trials in Asian populations, so the authors caution against extrapolating elsewhere; esophageal cancer was not significantly affected (1.22, 0.59-2.54). One author is at IARC.

17. 17
    Eaton KA, Brooks CL, Morgan DR, Krakowka S. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets.Infect Immun · 1991 · 59(7):2470-5doi:10.1128/iai.59.7.2470-2475.1991 · PMID 2050411

    A urease-weak mutant (0.4% of parental urease activity, otherwise identical) was given to gnotobiotic (germ-free) piglets: all 7 piglets given the parental strain became infected and none of 10 given the urease-negative strain did. Animal evidence that urease is essential for colonization.

18. 18
    Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. Attempt to fulfil Koch's postulates for pyloric Campylobacter.Med J Aust · 1985 · 142(8):436-9doi:10.5694/j.1326-5377.1985.tb113443.x · PMID 3982345

    The self-experiment: a volunteer (Marshall himself) with a histologically normal stomach swallowed the bacterium, developed a mild illness lasting 14 days, and had histologically proven gastritis on day 10 that had largely resolved by day 14. One subject; it showed the organism can cause acute gastritis, not that it causes ulcers or cancer.

19. 19
    Asano N, Iijima K, Koike T, Imatani A, Shimosegawa T. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review.World J Gastroenterol · 2015 · 21(26):8014-20doi:10.3748/wjg.v21.i26.8014 · PMID 26185372

    Review: about 90% of gastric MALT lymphomas are H. pylori-related and roughly 10% are not; the translocation t(11;18)(q21;q21), which makes the API2-MALT1 fusion protein and activates NF-κB, is more common in H. pylori-negative tumors and marks those that will not respond to eradication. A review; names the subset in which eradication fails.

20. 20
    Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention.Cancer Res · 1992 · 52(24):6735-40PMID 1458460

    The Correa model: a sequence from chronic gastritis to atrophy to intestinal metaplasia to dysplasia to carcinoma, with the early stages linked to salt and H. pylori and nitrosating agents proposed as candidate carcinogens. An award lecture synthesizing pathology and epidemiology; no PubMed DOI on the record.

21. 21
    Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors.Proc Natl Acad Sci U S A · 1996 · 93(25):14648-53doi:10.1073/pnas.93.25.14648 · PMID 8962108

    Defined the cag pathogenicity island: a ~40-kb block of DNA present only in type I (disease-associated) strains, carrying cagA and genes resembling a bacterial secretion system; inactivating several abolished induction of interleukin-8 in gastric cells. Molecular. Several authors were employed by Chiron Vaccines, a commercial vaccine maker.

22. 22
    Ohnishi N, Yuasa H, Tanaka S, et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse.Proc Natl Acad Sci U S A · 2008 · 105(3):1003-8doi:10.1073/pnas.0711183105 · PMID 18192401

    Mice engineered to make CagA throughout the body or in the stomach developed gastric epithelial hyperplasia and, in some, adenocarcinomas of the stomach and small intestine, plus leukemias and B-cell lymphomas; mice making a phosphorylation-resistant CagA did not. Called 'first direct evidence' that CagA is a bacterium-derived oncoprotein. Animal (transgenic mice), not natural infection.

23. 23
    Hatakeyama M. Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis.Cell Host Microbe · 2014 · 15(3):306-16doi:10.1016/j.chom.2014.02.008 · PMID 24629337

    Review: CagA delivered into gastric cells deregulates the SHP-2 oncoprotein and other pathways, acting as an oncoprotein that also drives genetic instability; but because CagA is not needed to maintain an established cancer, carcinogenesis is 'hit-and-run,' CagA's early push later taken over by accumulated genetic and epigenetic changes. A review.

24. 24
    Ansari S, Yamaoka Y. Role of vacuolating cytotoxin A in Helicobacter pylori infection and its impact on gastric pathogenesis.Expert Rev Anti Infect Ther · 2020 · 18(10):987-996doi:10.1080/14787210.2020.1782739 · PMID 32536287

    Review of VacA, the vacuolating cytotoxin: present in almost all strains but toxigenic only in some, it causes cell vacuolation and apoptosis, helps the bacterium persist and evade antibiotics and host defense, and may act with CagA. A review; a US NIH-funded laboratory with the senior author also at Baylor College of Medicine.

25. 25
    Panchal PC, Forman JS, Blumberg DR, Wilson KT. Helicobacter pylori infection: pathogenesis.Curr Opin Gastroenterol · 2003 · 19(1):4-10doi:10.1097/00001574-200301000-00002 · PMID 15699887

    Review of pathogenesis: the cag pathogenicity island regulates signaling and interleukin-8 secretion in epithelial cells, with roles identified for VacA, urease and host responses including apoptosis and nitric oxide, part of which the bacterium limits to evade immunity. A short review of mechanisms.

26. 26
    Peek RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas.Nat Rev Cancer · 2002 · 2(1):28-37doi:10.1038/nrc703 · PMID 11902583

    Review: gastric adenocarcinoma is associated with H. pylori, yet only a small fraction of colonized people develop it, and strain genotype (such as cag status) and host genotype shift the risk by changing inflammation and epithelial physiology. A review emphasizing that infection is necessary but far from sufficient.

27. 27
    Lazarate Cuba RJ, Quigley EM. A History of the Discovery of Helicobacter Pylori, with Special Reference to Giulio Bizzozero.J Gastrointestin Liver Dis · 2024 · 33(4):535-541doi:10.15403/jgld-5942 · PMID 39733316

    A historical review: though H. pylori was introduced to science by Warren and Marshall in 1983, a closely related Helicobacter had been described about a hundred years earlier, by the Italian pathologist Giulio Bizzozero, in the canine stomach; spiral gastric organisms were seen and forgotten repeatedly before 1983. A secondary history, included for the pre-discovery record.

28. 28
    Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma.N Engl J Med · 1991 · 325(16):1127-31doi:10.1056/NEJM199110173251603 · PMID 1891020

    Nested case-control study within a 128,992-person cohort, using serum stored since the 1960s, mean 14.2 years before diagnosis: 84% of 109 confirmed gastric adenocarcinomas (excluding gastro-esophageal junction) had prior H. pylori infection versus 61% of matched controls, odds ratio 3.6 (95% CI 1.8-7.3); junction and cardia tumors not linked. Human observational; the authors called the bacterium a possible cofactor.

29. 29
    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(9636):392-7doi:10.1016/S0140-6736(08)61159-9 · PMID 18675689

    544 patients after endoscopic resection of early gastric cancer, randomized to eradication or control: new (metachronous) cancers in 9 versus 24 at 3 years, odds ratio 0.353 (95% CI 0.161-0.775). Open-label (patients and clinicians unblinded); funded by the Hiroshima Cancer Seminar Foundation.

30. 30
    Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis.Lancet Infect Dis · 2018 · 18(3):318-327doi:10.1016/S1473-3099(17)30753-3 · PMID 29276051

    The WHO 2017 priority list of antibiotic-resistant bacteria for drug development: clarithromycin-resistant H. pylori is placed in the high-priority tier among community-acquired pathogens. Commissioned by WHO.

31. 31
    Choi IJ, Kim CG, Lee JY, et al. Family History of Gastric Cancer and Helicobacter pylori Treatment.N Engl J Med · 2020 · 382(5):427-436doi:10.1056/NEJMoa1909666 · PMID 31995688

    Double-blind, placebo-controlled trial in 1,676 first-degree relatives of gastric-cancer patients, median follow-up 9.2 years: eradication therapy cut gastric cancer to 1.2% versus 2.7% on placebo, hazard ratio 0.45 (95% CI 0.21-0.94); among those in whom the bacterium was actually eradicated it was 0.8% versus 2.9% with persistent infection (hazard ratio 0.27). Funded by the National Cancer Center, South Korea.

32. 32
    de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis.Lancet Glob Health · 2019 · 8(2):e180-e190doi:10.1016/S2214-109X(19)30488-7 · PMID 31862245

    The previous estimate (GLOBOCAN 2018): 2.2 million infection-attributable cancers, H. pylori the leading cause at 810,000 (age-standardized incidence rate 8.7 per 100,000). IARC-funded; the 810,000 figure next to the 2024 figure of 760,000 shows the count easing as prevalence falls.

33. 33
    Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden of cancers attributable to infections in 2012: a synthetic analysis.Lancet Glob Health · 2016 · 4(9):e609-16doi:10.1016/S2214-109X(16)30143-7 · PMID 27470177

    GLOBOCAN 2012 estimate: 2.2 million of 14 million new cancers (15.4%) attributable to infection, H. pylori leading at 770,000. IARC authors, funded by Fondation de France.

34. 34
    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(6):607-15doi:10.1016/S1470-2045(12)70137-7 · PMID 22575588

    The founding paper of the series (GLOBOCAN 2008): a population-attributable fraction of 16.1%, about 2 million cancers, with H. pylori, the hepatitis viruses and HPV responsible for 1.9 million; about 30% of infection-attributable cases in people under 50. Funded by FINOVI and the Gates Foundation.

35. 35
    Morgan E, Arnold M, Camargo MC, et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020-40: A population-based modelling study.EClinicalMedicine · 2022 · 47:101404doi:10.1016/j.eclinm.2022.101404 · PMID 35497064

    IARC estimate of the disease H. pylori mainly causes: about 1.1 million new gastric cancers and 770,000 deaths in 2020, highest in eastern Asia, projected to rise to about 1.8 million cases and 1.3 million deaths by 2040, with primary prevention through H. pylori eradication named as key. A modeling study.

36. 36
    Park JY, Georges D, Alberts CJ, Bray F, Clifford G, Baussano I. Global lifetime estimates of expected and preventable gastric cancers across 185 countries.Nat Med · 2025 · 31(9):3020-3027doi:10.1038/s41591-025-03793-6 · PMID 40624406

    IARC lifetime projection: across 185 countries about 15.6 million lifetime gastric cancers (95% uncertainty interval 14.0-17.3 million) are expected in the cohorts born 2008-2017, 76% attributable to H. pylori, two-thirds in Asia; 42% of cases will fall in historically lower-incidence areas as populations change, with the future sub-Saharan African burden possibly six times its 2022 level. The IARC authors call for population-based H. pylori screen-and-treat. A modeling study.

37. 37
    Miura M, Ohnishi N, Tanaka S, Yanagiya K, Hatakeyama M. Differential oncogenic potential of geographically distinct Helicobacter pylori CagA isoforms in mice.Int J Cancer · 2009 · 125(11):2497-504doi:10.1002/ijc.24740 · PMID 19588494

    Transgenic mice making East Asian CagA (with the EPIYA-D segment, a high-affinity SHP-2 binding site) developed more tumors than mice making Western CagA (EPIYA-C, lower affinity), which the authors offer as one reason gastric cancer is commoner in East Asia. Animal; a mechanistic correlate of a geographic difference, not a human measurement.

38. 38
    De Koster E, Buset M, Fernandes E, Deltenre M. Helicobacter pylori: the link with gastric cancer.Eur J Cancer Prev · 1994 · 3(3):247-57doi:10.1097/00008469-199403030-00003 · PMID 8061590

    A 1994 review setting the Correa cascade beside the early epidemiology, including three prospective nested case-control studies showing infection precedes gastric adenocarcinoma, and noting eradication had cured cases of low-grade gastric lymphoma. A review restating findings, not new data.

39. 39
    Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis.Gut · 2015 · 64(9):1353-67doi:10.1136/gutjnl-2015-309252 · PMID 26187502

    Global consensus recommending a new etiology-based classification of gastritis for the ICD-11 and, where feasible, eradication of H. pylori before preneoplastic changes develop to minimize later complications. A consensus report, reached by a structured expert vote.

40. 40
    Shah SC, Wang AY, Wallace MB, Hwang JH. AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review.Gastroenterology · 2025 · 168(2):405-416.e1doi:10.1053/j.gastro.2024.11.001 · PMID 39718517

    American Gastroenterological Association expert review: names H. pylori eradication as primary prevention and endoscopic screening and surveillance of precancerous conditions such as gastric intestinal metaplasia as secondary prevention, and identifies US high-risk groups (first-generation immigrants from high-incidence regions, first-degree relatives of gastric-cancer patients, certain hereditary syndromes). A best-practice update, not a systematic review.

41. 41
    Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions.Gastroenterology · 2018 · 155(5):1372-1382.e17doi:10.1053/j.gastro.2018.07.007 · PMID 29990487

    178 studies, 66,142 isolates, 65 countries: resistance to clarithromycin, metronidazole and levofloxacin was at or above 15% in most WHO regions and rising, and clarithromycin resistance was strongly associated with failure of clarithromycin-containing treatment (odds ratio 6.97, 95% CI 5.23-9.28). A meta-analysis with high heterogeneity.

42. 42
    Patel A, Laine L, Moayyedi P, Wu J. AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice: Expert Review.Gastroenterology · 2024 · 167(6):1228-1238doi:10.1053/j.gastro.2024.06.038 · PMID 39269391

    American Gastroenterological Association expert review on potassium-competitive acid blockers (P-CABs): Best Practice Advice 7 states that clinicians should use P-CABs in place of proton-pump inhibitors in eradication regimens for most patients with H. pylori infection. A best-practice update, not a systematic review.

43. 43
    Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer.N Engl J Med · 2018 · 378(12):1085-1095doi:10.1056/NEJMoa1708423 · PMID 29562147

    Double-blind, placebo-controlled trial, 470 patients after resection of early gastric cancer or high-grade adenoma, median follow-up 5.9 years: metachronous cancer in 7.2% of the treated versus 13.4% of the placebo group, hazard ratio 0.50 (95% CI 0.26-0.94), and improvement in gastric-body atrophy in 48.4% versus 15.0%. Funded by the National Cancer Center, South Korea.

44. 44
    Islami F, Kamangar F. Helicobacter pylori and esophageal cancer risk: a meta-analysis.Cancer Prev Res (Phila) · 2008 · 1(5):329-38doi:10.1158/1940-6207.CAPR-08-0109 · PMID 19138977

    Meta-analysis of 19 studies: H. pylori was inversely associated with esophageal adenocarcinoma (summary odds ratio 0.56, 95% CI 0.46-0.68), the protective signal confined to CagA-positive strains (0.41, 0.28-0.62), and the authors suggest the decline of H. pylori may partly explain the rise of esophageal adenocarcinoma in the West. Human observational; an association, and the same organism is a proven stomach carcinogen.