Diagnostic value of HE4 in ovarian cancer: A meta-analysis

Abstract

Objective: To analyze and evaluate the overall diagnostic value of Serum Human Epididymis Protein 4 (HE4) in ovarian cancer.

Methods: We searched PubMed, EMBASE, Cochrane Library and Web of Science databases to collect articles in English that evaluated the diagnostic value of HE4 in patients with gynecological or pelvic masses. Two reviewers independently assessed the methodological quality of each study using the QUADAS-2 tool. A chart of literature quality was made using Revman 5.3 software. Finally, we built Summary Receiver Operating Characteristic (SROC) curves, Hierarchical Summary Receiver Operating Characteristic (HSROC) models, a Deek's funnel figure as well as a meta-analysis of included studies using STATA12.0 and Meta-Disc1.4 software.

Results: Eighteen studies from the published literature met all inclusion criteria for this analysis. Remarkably, no publication bias was found among the included studies. HE4 had a pooled sensitivity of 81% (95% confidence interval (CI): 77-85) and a pooled specificity of 91% (95% CI: 86-93,). Overall, the positive likelihood ratio (PLR) was 8.2, (95% CI: 5.60-12.00,) the negative likelihood ratio (NLR) was 0.21 (95% CI: 0.17-0.26), the diagnostic odds ratio (DOR) was 39 (95% CI: 25-62), the AUC of SROC was 0.91, and Cochrane-Q value was 86.02.

Conclusions: HE4 is a valuable marker in the clinical diagnosis of ovarian cancer with both high AUC and Cochrane-Q. More studies are needed to determine if HE4 in the range of 100 mmol/L ≤ cutoff≤150 mmol/L than 60 mmol/L＜cutoff＜100 mmol/L holds more diagnostic value.

Keywords: Diagnostic; HE4; Meta-analysis; Ovarian cancer.