Meta-analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophic gastritis screening

Abstract

Aim:To assess the validity of the measurement of pepsinogen I and II as a screening test for gastric cancer and pre-malignant lesions, namely low-grade dysplasia, both in the general population and in selected groups of patients. Methods:A meta-analysis of sensitivity and specificity results from individual papers on the use of the pepsinogen test. An intrinsic cut-off effect was assumed and a random effect model was used for pooling.Results: Forty-two data sets were included: 27 (64%) population-based screening studies (n=296,553) and 15 (36%) sets of selected individuals (n=4385). Homogenous sensitivity and diagnostic odds ratio (DOR) estimates were found in studies using both pepsinogen I levels and pepsinogen I/II ratio calculations. Pooled pairs of sensitivity and false positive rates (FPr) for pepsinogen I ≤70; pepsinogen I/II ratio ≤3, pepsinogen I ≤50; pepsinogen I/II ratio ≤3, and pepsinogen I ≤30; pepsinogen I/II ratio ≤2, were sensitivity 77%/FPr 27%, sensitivity 68%/FPr 31%, and sensitivity 52%/FPr 84%, respectively. Positive predictive values (PPV) varied between 0.77% and 1.25%, and negative predictive values (NPV) varied between 99.08% and 99.90%. In selected groups, pooling was only possible when considering pepsinogen I ≤70; pepsinogen I/II ratio ≤3: giving sensitivity 57%, specificity 80%, PPV 15% and NPV 83%. As for the diagnosis of dysplasia, studies considering pepsinogen I <50; pepsinogen I/II ratio <3 obtained sensitivity 65% and specificity ranging from 74%-85%, both with NPV >95%. Conclusion:Pepsinogen test definition should include pepsinogen I/II ratio as consistency was obtained, both in population based studies and in selected groups for those studies that used pepsinogen I serum levels together with pepsinogen I/II ratio for screening for gastric cancer in highincidence regions other than Japan. Further studies of this test in the management of high-risk patients seem to be worthwhile.

Association between serum pepsinogens and polymorphismof PTPN11 encoding SHP‐2 among Helicobacter pylori seropositive Japanese

“…[41][42][43] We utilized the validated cutoff levels employed routinely in Japan, namely, a PG I level of < 70 ng/ml and a PG I:II ratio of < 3.0. [44][45][46] Thus, we feel confident that the designation of atrophy was accurate and reflected the important histologic entity of corpus atrophy. In summary, we have found that a polymorphism in the PTPN11 gene that encodes SHP-2 increases the risk of gastric atrophy in H. pylori-positive patients.…”

Serum pepsinogen levels and their infl uencing factors: A population-based study in 6990 Chinese from North China

“…However, the limited knowledge about their characteristics in different populations and the significant differences in methodologies may prejudice the assessment of consistency. For instance, different cut-off values are used for the positive definition when either PGⅠ levels or both PGⅠand PGⅡ levels are considered [11][12][13] . Furthermore, due to few cohort studies have been done in Chinese, the population-based data on serum PG levels and their influencing factors, such as age, sex, the presence of different gastric diseases and H pylori infection, are limited [14,15] .…”

Challenges in evaluation of screening for gastric cancer among men based on nonrandomized design

“…Therefore, early identification and endoscopy of subjects with AG may facilitate the diagnosis of gastric cancer at an early stage, and may enable treatment of premalignant gastric lesions (intramucosal neoplasias) in an asymptomatic phase [6][7][8][9]. A low serum level of pepsinogen I (SPGI) is a reliable biomarker of AG and is, therefore, a tool to noninvasively delineate subjects with advanced AG who need a prompt diagnostic upper GI endoscopy because of increased cancer risk [1][2][3][4]. Correspondingly, it is conceivable that an early diagnosis of AG with a biomarker test followed with a diagnostic upper GI endoscopy will improve the cancer survival, resulting also in decrease of premature mortality.…”

“…It was known that SPGI levels of 25 microg/l or less indicate advanced (moderate or severe) atrophic gastritis (AG) in the gastric corpus and fundus with high reliability [1][2][3][4]. However, the indicators of structure, process, and outcome related to screening were completely unknown.…”