Diagnostic value of HE4 for ovarian cancer: a meta-analysis

Clin Chem Lab Med. 2012 Feb 3;50(8):1439-46. doi: 10.1515/cclm-2011-0477.


Background: Ovarian cancer (OC) is the second most common gynecological cancer and the first cause of death from gynecological malignancy in Western Europe and the USA. While human epididymis-specific protein 4 (HE4) has been reported as a predictive diagnostic index, it has not been widely accepted because of inconsistent conclusions. The aim of this study was to evaluate the diagnostic value of HE4 systematically for ovarian cancer.

Methods: All relevant original studies about HE4 in the diagnosis of ovarian cancer published from January 1974 to May 2011 were retrieved. By measuring methodological qualities, 12 papers were selected for this study, while 531 articles were searched. The overall diagnostic sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-), and area under the receiver operating characteristic curve (AUC-ROC) were used to evaluate the diagnostic value of HE4 for ovarian cancer using the Meta-DiSc statistical software.

Results: There were 2607 subjects included in this meta-analysis. The sensitivity, specificity, LR+ and LR- (95% confidence interval) of HE4 was 0.800 (0.770-0.827), 0.916 (0.902-0.929), 10.271 (6.982-15.109) and 0.228 (0.181-0.287), respectively. The area under the summary receiver operating characteristic (sROC) curve of HE4 was 0.946. The index of Q* was 0.885.

Conclusions: HE4 was found to be better than CA125 as an auxiliary indicator for the diagnosis of ovarian cancer in terms of better sensitivity, specificity, LR+ and LR-.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood
  • Female
  • Humans
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / diagnosis
  • Proteins / metabolism*
  • WAP Four-Disulfide Core Domain Protein 2


  • Biomarkers, Tumor
  • CA-125 Antigen
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human