Human epididymis protein 4 for differential diagnosis between benign gynecologic disease and ovarian cancer: a systematic review and meta-analysis

Abstract

Objectives: Human epididymis protein 4 (HE4) is a new biomarker for the detection of ovarian cancer. The objective of this review was to assess by meta-analysis the overall diagnostic accuracy of HE4 assay in differentiating malignant ovarian tumors from benign gynecology diseases.

Study design: The MEDLINE, EMBASE, and Cochrane Library databases were searched for studies published up to June 2012 that evaluated HE4 accuracy. Meta-analysis was used to calculate sensitivity, specificity, the positive likelihood ratio (PLR), the negative likelihood ratio (NLR) and the area under curve (AUC).

Results: A total of 11 studies with 3395 patients who fulfilled all inclusion criteria were considered in the analysis. No publication bias was found. HE4 had a pooled sensitivity of 0.74 (95% confidence interval (CI), 0.72-0.76) and a pooled specificity of 0.87 (95% CI, 0.85-0.89). Overall, the positive likelihood ratio was 8.04 (95% CI, 4.89-13.21) and the negative likelihood ratio was 0.27 (95% CI, 0.22-0.34). When HE4 was combined with CA125, the sensitivity was higher than that of HE4 alone at the expense of lower specificity.

Conclusions: The measurement of serum HE4 is a useful method for differential diagnosis between benign gynecologic disease and ovarian cancer.