European Journal of Cardiovascular Medicine

Gastric adenocarcinoma ranks among the top causes of cancer mortality globally, particularly in regions with high prevalence of Helicobacter pylori (H. pylori) infection. Chronic inflammation induced by H. pylori is now understood to be a central driver of the Correa cascade—a histopathological progression from chronic gastritis through atrophic gastritis, intestinal metaplasia, dysplasia, and eventually carcinoma. Despite increasing evidence of this progression, the temporal and mechanistic links between inflammation and malignancy remain inadequately explored in certain populations, such as semi-urban Indian cohorts.

Recent studies have clarified how H. pylori triggers sustained inflammatory responses, altering gastric epithelial cells and microenvironments in ways that favour oncogenesis. Wang et al. described how H. pylori-induced cytokine storms lead to oxidative DNA damage and gastric mucosal remodeling, key precursors to malignant transformation [1]. Similarly, Kumar et al. demonstrated that chronic inflammation modulates exosome function and cellular signalling, fostering tumour-promoting environments [2].

Peek and Amieva emphasized that beyond inflammation, H. pylori virulence factors like CagA interfere with host signalling pathways, disrupting cellular junctions and enhancing epithelial cell turnover, thereby promoting neoplastic potential [3]. Dincă et al. further showed how inflammatory mediators like IL-1β and TNF-α are persistently upregulated in infected mucosa, reinforcing chronic inflammatory states that favour carcinogenesis [4].

Longitudinal studies by Yang et al. revealed that chronic H. pylori-induced inflammation leaves lasting mucosal imprints, even post-eradication, suggesting that irreversible preneoplastic changes may be seeded early during infection [5]. In a meta-analysis, Zhang and Zhang outlined how H. pylori-associated inflammation affects genes like p21, increasing epithelial proliferation and mutation accumulation [6].

Beyond microbial virulence, epigenetic regulation has emerged as a key pathway by which inflammation promotes cancer. Carrasco and Corvalan documented hypermethylation of tumour suppressor genes in chronically inflamed gastric tissues [7].

Hedgehog/GLI signalling pathways, as discussed by Wessler et al., further illustrate how chronic inflammatory cues convert normal stem-cell-like compartments into malignancy-prone niches [8]. Valenzuela and Canales provided additional evidence for H. pylori-induced inflammation driving both DNA methylation and histological transitions associated with early gastric carcinogenesis [9].

These findings collectively highlight that inflammation is not merely a symptom but a fundamental architect of oncogenic change in H. pylori-infected gastric tissue. This study aims to prospectively examine this inflammatory-carcinogenic trajectory in an Indian semi-urban population over a two-year period.

A total of 80 patients with histologically confirmed H. pylori infection were enrolled in the study. The mean age group distribution was weighted toward middle-aged and older adults, with 32.5% aged 31–50 years, 28.8% aged 51–65 years, and 20.0% older than 65 years. Males constituted 61.2% of the cohort. Most patients (50.0%) belonged to the low socioeconomic stratum.

A significant proportion reported gastrointestinal symptoms at baseline, with epigastric pain in 76.2%, dyspepsia in 62.5%, and unintentional weight loss in 43.8% of cases. Lifestyle risk factors were common, with 36.2% reporting current smoking and 28.8% reporting alcohol use. Regarding comorbid conditions, 41.2% had at least one chronic illness, with hypertension and diabetes being the most prevalent.

These baseline demographic and clinical characteristics are detailed in Table 1.

Table 1. Baseline Demographic and Clinical Characteristics

Baseline Histopathologic Findings

All enrolled patients (100%) were confirmed to be H. pylori-positive based on histological evaluation. At baseline, moderate chronic inflammation was the most common histologic finding, observed in 51.2% of patients, followed by severe inflammation in 28.8% and mild inflammation in 20.0%.

Intestinal metaplasia, a well-known preneoplastic lesion, was present in 26.2% of cases, indicating a substantial burden of mucosal transformation even before the onset of dysplasia. Dysplastic changes were observed in 11.2% of patients at enrollment, suggesting an elevated baseline risk for malignant progression in a notable minority of the cohort.

Details of histologic features at baseline are presented in Table 2.

Table 2. Baseline Histopathologic Findings

Longitudinal Progression of Histopathology

Histopathologic progression was observed in a stepwise pattern over the 24-month follow-up period. At 6 months, all patients remained in the chronic inflammation category. By 12 months, 12.5% of patients had progressed to intestinal metaplasia, and 6.2% showed early dysplastic changes. This trend continued over time, with 31.2% showing metaplasia and 15.0% developing dysplasia by the end of the study period.

The incidence of gastric adenocarcinoma rose notably in the latter half of follow-up, with 8.7% (n=7) diagnosed by 24 months. These findings support the continuum of histologic transformation from inflammation through metaplasia and dysplasia to carcinoma.

The progression profile is summarized in Figure 1, highlighting the cumulative and overlapping transitions across disease stages.

Figure 1. Progression of Gastric Mucosal Changes in H. pylori–Positive Patients Over 24 Months

Stacked bar plot illustrating the histologic progression among 80 patients with biopsy-confirmed H. pylori infection over a 24-month period. The graph shows the decreasing proportion of patients with isolated chronic inflammation and the concurrent rise in intestinal metaplasia, dysplasia, and adenocarcinoma. Histologic changes were assessed at 6-month intervals via upper endoscopy with biopsy. The cumulative trend supports the inflammation–metaplasia–dysplasia–carcinoma sequence.

Incidence of Gastric Adenocarcinoma

At the conclusion of the 24-month follow-up, 5 out of 80 patients (6.2%) were diagnosed with histologically confirmed gastric adenocarcinoma. Stratification by baseline dysplasia status revealed a notably higher incidence in patients who had dysplasia at enrollment.

Among patients with baseline dysplasia, the risk of developing adenocarcinoma was markedly elevated compared to those without dysplasia, with a relative risk of 5.26 (95% CI, 1.01 to 27.37). Despite the observed trend, this difference did not reach conventional levels of statistical significance (χ² = 1.88; df = 1; p = 0.1706), likely due to the limited number of events and sample size.

These findings suggest a substantially increased risk of malignant transformation in dysplastic gastric mucosa and support the need for closer surveillance in such individuals.

Predictors of Malignant Transformation

To identify independent predictors of gastric adenocarcinoma, a multivariable logistic regression analysis was performed using baseline characteristics. Variables included age, smoking status, presence of dysplasia and intestinal metaplasia, and the severity of chronic inflammation.

The presence of baseline dysplasia was associated with an increased odds of malignant transformation (OR, 17.04; 95% CI, 0.92 to 315.72; p = 0.057), approaching statistical significance. Intestinal metaplasia similarly showed a strong association (OR, 22.21; 95% CI, 0.96 to 513.55; p = 0.053). Smoking was also associated with higher odds of progression (OR, 7.97; 95% CI, 0.45 to 140.83), though not statistically significant (p = 0.156). Neither age nor inflammation severity emerged as significant predictors.

These results suggest that dysplasia and metaplasia may serve as potent early markers for cancer risk and merit intensified surveillance.

The regression findings are summarized in Table 3.

Table 3. Predictors of Malignant Transformation: Multivariable Logistic Regression

Time-to-Event Analysis

Cancer-free survival over the 24-month follow-up period was estimated using Kaplan–Meier survival analysis, stratified by baseline dysplasia status. Patients with dysplasia at enrollment demonstrated a notably lower probability of remaining cancer-free compared to those without dysplasia. The divergence between survival curves became more pronounced after 12 months, suggesting a time-dependent separation of risk.

The cumulative incidence of gastric adenocarcinoma was higher in the dysplasia group, although the number of events remained limited. Censoring was appropriately accounted for in both strata, and confidence intervals widened progressively over time due to smaller numbers at risk.

This stratified survival profile underscores the prognostic relevance of early histological abnormalities and supports the utility of baseline dysplasia as a predictive marker for malignant transformation.

Figure 2. Kaplan–Meier Curve for Cancer-Free Survival by Baseline Dysplasia Status

Kaplan–Meier survival curves showing the probability of remaining free from gastric adenocarcinoma over a 24-month period among patients with (red) and without (blue) baseline dysplasia. Patients with baseline dysplasia exhibited a steeper decline in survival probability, particularly after 12 months. The shaded regions indicate 95% confidence intervals. Censoring was incorporated in the model, and patients without events were appropriately retained in the risk set until their last follow-up.

This study has several limitations. First, the modest sample size and single-centre design may limit the generalizability of our findings. Second, histological interpretation, though standardized, may be subject to interobserver variability. Third, potential confounders such as dietary habits, genetic predispositions, or environmental exposures were not controlled. Lastly, follow-up duration, while adequate for early neoplastic transformation, may not capture long-term malignant outcomes.

In this prospective cohort study, baseline dysplasia and intestinal metaplasia emerged as strong predictors of gastric adenocarcinoma among H. pylori-positive patients. These findings support the implementation of risk-based histologic surveillance strategies in endemic regions and reinforce the critical role of early detection in mitigating gastric cancer progression.

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