Residual gastric cancer risk after Helicobacter pylori eradication: Mucosal immune trajectories (Review)

Helicobacter pylori is the leading modifiable cause of noncardia gastric cancer.Eradication lowers the incidence of primary and metachronous gastric neoplasia, yet a clinically meaningful risk remains once extensive atrophy, intestinal metaplasia or dysplasia is established.Current surveillance incorporates infection status and structural disease burden but does not directly assess biological recovery of the gastric mucosa.The present review examined whether mucosal immune trajectories after eradication are heterogeneous and whether localized immune measurements could explain variation in residual risk beyond morphology and epithelial-field alterations.Single-cell and spatial studies of human tissue have identified infection-and precursor-associated changes in myeloid differentiation, antigen presentation, T-cell states, metaplastic epithelium and stroma.Longitudinal evidence is less developed.Selected mucosal T-cell measurements support reversibility of specific responses, whereas gene-expression, histologic and microbiome trajectories provide molecular, structural or contextual evidence.Outcome-linked CD8-associated trajectories provide the closest currently available clinical-outcome immune evidence, but remain non-functional proxies derived from a post-resection population.A 2026 human single-cell study further identified persistent stromal and immunosuppressive niche features in post-eradication chronic atrophic gastritis, but did not provide paired longitudinal immune-function measurements or prospective neoplastic outcomes.Among the studies identified through the present search, none combined confirmation of eradication, paired measurements of immune function, concurrent assessment of the epithelial field and prospective dysplasia or cancer outcomes in individuals without previous gastric neoplasia.Therefore, the available evidence supports heterogeneous tissue recovery rather than a validated persistent immune state.Clinical translation would require reproducible functional immune activity, or a functionally validated proxy, together with independent outcome association, external validation and a clinically meaningful improvement in surveillance decisions beyond established histologic staging and lesion extent.Until such evidence is available, candidate immune markers should remain research tools and should not modify guideline-based surveillance.Contents 1. Introduction 2. Literature search and evidence appraisal 3. Current clinical framework and its limits 4. A falsifiable tissue-based framework 5. Immune remodeling during chronic H. pylori infection 6. Metaplastic and stromal substrates of persistence 7. Human evidence after eradication 8. Discussion 9.