Hp infection can cause excessive proliferation of gastric epithelial cells, increasing the risk of malignant transformation of gastric epithelial cells, which may be the key to Hp-induced gastric carcinogenesis. It has been found that the relative risk rate of intraepithelial neoplasia in Hp-infected patients is 15.5 (95% confidence interval 6.42-37.2), while the relative risk rate in Hp-uninfected patients is 0.90 (95% confidence interval 0.37-2.17), suggesting that HP infection is closely related to gastric intraepithelial neoplasia. The possible mechanisms of HP infection and the occurrence of gastric mucosal intraepithelial neoplasia are briefly reviewed. The pathogenesis of HP is a non-invasive bacterium that colonizes the human gastric mucosa between the surface and the mucus layer, and it can naturally colonize the human gastric mucosa in a continuous and specific manner. adhesion factors, phospholipases, and cellular vacuolar toxins. The immune response induced by HP infection has become a hot topic in recent years, with reduced production of IFNr and overproliferation of CD8 marker-producing T cells in HP infection; the type of cytokines present in the host immune response in infected patients is a typical defective Th1 response, resulting in a prolonged HP infection; lymphocytes and plasma cells can secrete IgG and IgM after HP infection Lymphocytes and plasma cells can secrete IgG and IgM after HP infection, causing damage to gastric mucosal cells through this associated local and systemic immune response. It has been found that there are many strain variants of Hp that determine the virulence and pathogenicity of the bacteria. While Hp virulence factors can produce local pathogenic effects associated with disease development, the differences in pathogenicity of Hp strains are mainly related to the polymorphism of their virulence genotypes. In recent years, differences in protein expression levels and activity due to gene polymorphisms at the same locus have gradually become a new explanation for the clinical outcome of Hp-infected hosts, and with a series of new pathogenic genes (BabA, SabA, OipA, DupA, etc.) being uncovered, it is conducive to further elucidating the pathogenic mechanism of Hp and providing new meaningful prognostic judgment and clinical treatment for Hp infection The results of the study are summarized as follows The mechanism of HP infection induced gastric mucosal intraepithelial neoplasia HP infection can induce the proliferation of gastric mucosal epithelial cells, and the mechanism may be related to the inflammatory response and release of inflammatory mediators caused by HP infection. The mechanism of HP infection induced intraepithelial neoplasia in gastric mucosa is related to the following. It is believed that HP infection first causes inflammatory changes in the gastric mucosa, which further damages the gastric mucosal epithelium and eventually leads to the appearance of intestinal epithelial hyperplasia and intraepithelial neoplasia. Intestinal epithelial hyperplasia is the result of long-term HP infection, while intraepithelial neoplasia is the result of long-term development of intestinal epithelial hyperplasia. From HP infection causing gastritis to the development of intraepithelial neoplasia and even gastric cancer may take more than a decade to decades. HP causes gastric cancer in an indirect manner, as the acute and chronic inflammation caused by HP infection increases the chance of DNA damage, and the HP stimulates the release of inflammatory mediators, AFP, and oxygen radicals from inflammatory cells in the gastric mucosa, causing excessive bacterial proliferation and increasing the chance of malignancy. HP induces the activation of NO pathway in macrophages and gastric epithelial cells, which leads to free radical production, resulting in point mutations and peroxidative DNA damage, which can lead to genetic modification of gastric epithelial cells, thus triggering carcinogenesis. It has also been suggested that the chronic persistent inflammatory response caused by HP infection is associated with telomerase activation and stem cell proliferation. In addition, chronic inflammation caused by HP infection can also stimulate cell proliferation, thus increasing the chance of DNA misreplication and damage by foreign mutagenic factors. 2, the role of HP-generated virulence factors HP-generated virulence factors can damage the gastric mucosa or cause an inflammatory response, leading to accelerated renewal of gastric mucosal epithelial cells, increasing the chance of DNA damage, thus causing intraepithelial neoplasia and cancer cell formation. The virulence genes of Hp with pathogenic significance include: Cag pathogenicity island (CagA) gene, specific vacuolar toxin A (VacA) gene, epithelial colony-inducing protein (IceA) allele, blood group antigen adhesion (BabA) gene, salivary acid adhesion (SabA) gene, etc. Among them, CagA and VacA are more closely related to gastric cancer. Schneller et al. reported that the CagA gene could be detected in about 70% of Hp-infected patients, and the incidence of intestinal mucosal metaplasia and intraepithelial neoplasia in the gastric sinus was increased in CagA-positive patients. Martyn et al. detected the presence and absence of HpDNA and CagA gene by polymerase chain reaction and specific probes in 2145 gastric biopsy specimens and found a strong association between CagA-positive Hp-infected patients and gastric precancerous lesions, while CagA-negative Hp-infected patients developed only chronic gastritis. CagA protein pathogenicity has been shown to include both non-phosphorylation-dependent and phosphorylation-dependent modes, with phosphorylated CagA protein binding to tyrosine- phosphatase containing SH2 (SHP-2), a c-Src homologue sequence. Activated SHP-2 leads to activation of the Erk1/2 pathway, which causes active mitosis and accelerated cell proliferation. Since CagA DNA contains multiple RNA degradation motifs, Ohnishi N et al. produced transgenic mice with humanized CagA modified with RNA degradation motifs, and they found that CagA transgenic mice developed gastric cancer and MALT lymphoma at week 72 [16].Vac A can affect inter-ion transport by acting on the Na+ – K+ – ATPase in the cell membrane Vac A can also interfere with the acid-secreting function of mural cells by affecting H+ – K+ – ATPase; Vac A can also affect the regulatory mechanism of growth factors in gastric mucosal cells and inhibit cell repair. Urease can decompose urea to produce ammonia, which can neutralize gastric acid and reduce acidity in the stomach, which helps the tricarboxylic acid cycle of bacterial mitochondria and affects the synthesis of ATP, causing impairment of cellular energy metabolism, resulting in atrophy and thinning of the glandular epithelium, thus forming gastric mucosal atrophy. 3, gastric mucosal epithelial cell proliferation and apoptosis imbalance The proliferation and apoptosis of gastric mucosal epithelial cells is a dynamic balance system, the occurrence of gastric mucosal epithelial intraepithelial neoplasia is closely related to excessive cell proliferation and apoptosis. It has been shown that many virulence factors produced by HP have damaging effects on gastric mucosal epithelial cells, which can promote excessive proliferation and abnormal apoptosis of gastric mucosal epithelial cells, thus increasing the chance of DNA damage and eventually causing intraepithelial neoplasia and even gastric cancer. In conclusion, HP infection is closely related to the occurrence of gastric mucosal intraepithelial neoplasia. HP infection may be the initiating factor for the development of gastric mucosal intraepithelial neoplasia, and it may be the initiating factor for the development of chronic gastritis to atrophic gastritis, intestinal epithelial metaplasia, intraepithelial neoplasia and gastric cancer. Although many studies have shown that HP infection is associated with an increased risk of gastric cancer, no direct evidence between HP infection and gastric cancer development has been found so far. With the in-depth study of HP in microbiology and molecular biology, we have reason to believe that researchers will gradually elucidate the mechanism of HP infection leading to gastric mucosal intraepithelial neoplasia and even carcinogenesis, thus opening a new pathway for the prevention and treatment of gastric cancer.