Background: Gastric cancer is one of the leading causes of death worldwide. Early detection of premalignant gastric lesions improves the prognosis of patients with this disease. One of the biomarkers studied for the early detection of premalignant gastric lesions is the pepsinogen I/II (PGI/II) index. PGI/II is a marker of parietal cell activity because variations in its levels reflect gastric morphophysiology. However, the available evidence on the diagnostic value of PGI/II as a biomarker for premalignant gastric lesions in patients with clinical suspicion and risk factors for gastric cancer is contradictory and needs to be synthesized. Methodology: Overview type review for diagnostic tests. Systematic reviews, meta-analyses, and primary articles related to the study object were included. The search was conducted in 4 databases and Google Scholar, without language or time restriction; each phase of the review was developed by two independent and parallel reviewers (NJ and JR) using the Ryyan tool and a predetermined form in Excel to extract the data. The risk of bias and quality of evidence were evaluated using the ROBIS and QUADAS-2 tools. Overlap of primary articles included in the systematic reviews (RS) was reported. No meta-analysis was performed due to the heterogeneity of the articles. Results: 18 articles, 4 systematic reviews, and 14 primary articles were included in this review, a total of 327,554 patients from 21 countries with an average median age of 57 years. The risk of bias was moderate in the systematic reviews and the quality of evidence in the primary articles. The overlap of cited articles was moderate. The median sensitivity was 50%, with a minimum value of 6% and a maximum of 100%, for specificity it was 74% with a maximum value of 95% and a minimum value of 22.5%. A high degree of heterogeneity was found in the included studies that remained after segmentation by cut-off points. Discussion: The pepsinogen I/II (PGI/II) index is a biomarker that has been studied for the early detection of gastric premalignant lesions. There is not enough evidence or homogeneous studies to recommend its use as a single diagnostic test. However, it has been successfully used as a complementary test to endoscopic studies in order to completely rule out the presence or progression of premalignant lesions. Conclusions: The included studies show high heterogeneity due to the variety in the studied population, utilization of different cutoff points, and techniques for pepsinogen detection. Additionally, we describe a high risk of bias related to patient selection, timing of sample collection, and interpretation of the index test. Considering the available evidence, the use of pepsinogen I/II levels is suggested as a complementary strategy to the standard reference in symptomatic populations with risk factors for atrophic gastritis aged between 59-74 years.
