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Eur J Obstet Gynecol Reprod Biol. 2013 Mar;167(1):81-5. doi: 10.1016/j.ejogrb.2012.10.036. Epub 2012 Dec 7.

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

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Clinic for Gynecology, Charite-Universitatsmedizin Berlin, Berlin, Germany.



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.


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).


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.


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

[Indexed for MEDLINE]

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