Timeframe for H. pylori to Cause Cancer
What is Helicobacter Pylori?
Helicobacter pylori (H. pylori) is a type of bacteria that colonises the gastric mucosal tissues and causes inflammation. Under the microscope, H. pylori are spiral-shaped, and they stain negative with Gram stain (a laboratory procedure where bacteria with harder membranes don't take up a specialised stain).
H. pylori is very prevalent - it is estimated that approximately half of the world's populations have H. pylori in their digestive systems.
As the infection with H. pylori causes inflammation, it is the primary cause of peptic ulcers, and is also recognised as one of the factors contributing to development of gastric carcinomas [1]. The severity of the H. pylori- associated inflammation varies greatly between individuals, from mild through chronic gastritis, and gastric cancers in some individuals [2].
Diagnosis of H. pylori
Modern medicine recognises multiple tests for H. pylori. An invasive option is an endoscopic biopsy, where a piece of tissue is taken and analysed in the laboratory by microscopy. Alternatively, bacterial culture can be performed, meaning that the sample will be kept at conditions ideal for bacterial growth, which is then observed.
Non-invasive testing methods include:
- Serology, where blood is investigated for the presence of antibodies against H. pylori;
- Stool antigen tests, where antibodies are used to detect molecular signature of H. pylori;
- (13)C Urea breath test, where the patient ingests a solution containing urea labeled with a non-radioactive carbon molecule, which is then detected as the patient breathes out [2].
Treatment and prognosis of H. pylori
The mainstay treatment for H. pylori involves a combination of a proton pump inhibitor (medication that decreases acid production in the stomach) and antibiotics. The course of treatment lasts between 7 and 14 days [3, 4, 5]. However, with growing antibiotic resistance, there are concerns that H. pylori will become more difficult to treat.
The prognosis of H. pylori varies. In peptic ulcer disease, eradication of H. pylori by antibiotics typically markedly improves the course of the disease [6]. However, without treatment, approximately 20% of patients develop peptic ulcers, and 1% of patients my progress to cancer [7]. However, currently, H. pylori can be successfully eradicated in 85% of patients [4].
The link between H. pylori and cancer
H. pylori causes inflammation in the stomach. Consequently, this creates an unstable cellular environment, where the tissue is destabilised and immune responses altered. H. pylori's virulence factors (molecules that help bacteria colonise its host), including CagA and VacA interfere with human signalling pathways, leading to persistent inflammation which cannot be resolved by the immune system [8, 9].
As inflammation is one of the main drivers of cancer, it is perhaps not surprising that a H. pylori lesion is ideally positioned to progress to cancer. Therefore, the International Agency for Cancer Research (IACR) has classified H. pylori as a Group 1 carcinogen, which means it's considered a definite cause of cancer [8, 10].
It is now well established that individuals with an active H. pylori infection have a higher risk of developing stomach cancer. However, there is discord in the literature as to what is the relative risk of developing stomach cancer. One study concluded that stomach cancer occurs up to 8 times more frequently in people infected with H. pylori [11]. Another study found that the risk is only 5 times higher in the infected cohort [12].
Additionally, there is now evidence that H. pylori can be associated with pancreatic and colorectal cancers [12]. However, while the link between H. pylori and cancer is well established, it is important to acknowledge that there are likely more factors contributing to development of stomach cancer, including genetic and environmental factors [13, 14].
Finally, it is important to note that not everyone infected with H. pylori will get cancer [15].
How long does it take for H. pylori to cause cancer?
The process of H. pylori carcinogenesis is slow and continuous. Generally, this takes between 20 and 40 years [16]. However, the exact timeframe can vary based on multiple factors, such as:
- The individual's immune system functionality (better functioning immune system can control the bacterial population for longer);
- The H. pylori strain that the patients is infected with (some strains are more aggressive and/or virulent than others);
- Genetic factors, though these are not fully understood;
- Environmental factors such as diet [8].
Prognosis of H. pylori-associated cancer
The relationship between H. pylori and stomach cancer is very interesting, and somewhat controversial. Generally, the presence of bacteria correlates with a worse prognosis. However, in the case of H. pylori, studies show that the presence of H. pylori may be a predictor of a more favourable outcome in patients with gastric cancers.
For example, a study of 261 patients who underwent a curative surgery found that those positive for H. pylori had a mean cancer-specific survival of 55.2 months and a mean disease-free survival (DFS) of 53.9 months. In contrast, patients negative for H. pylori had a mean cancer-specific survival of 45.1 months and a DFS of 43.7 months [17].
Another study conducted a meta-analysis of multiple published studies, and concluded that a positive H. pylori status was associated with an improved overall survival (hazard radio 0.81, where a value of more than 1 would mean a decrease in survival with the H. pylori infection) [18]. This was corroborated by another systematic review study [19].
However, cancer is a very complex disease. Therefore, some studies concluded the opposite - one study concluded a poorer prognosis of H. pylori infected patients, with a gastric cancer-specific survival of 30.2 months and a DFS of 28.7 months, compared to 39.8 months and 38.1 months, respectively, in H. pylori negative patients [20].
This discrepancy suggests a more complex interaction with a more complex interaction between H. pylori and gastric cancer. Interestingly, the impact of the H. pylori on cancer prognosis may vary depending on the population. For example, H. pylori infection was an indicator of good prognosis in European gastric cancer patients, but this was not in other populations [21].
Summary
While H. pylori is associated with development of stomach cancer, with a known mechanism where the bacteria destabilises the environment leading to development of ulcers which can progress to cancer, this process is slow, taking between 20 to 40 years on average. Interestingly, patients with a H. pylori infection tend to have a better prognosis, however this is dependent on a population the patient belongs to. Ultimately, the relationship between H. pylori and cancer is a complex one, requiring more research to fully understand it.
