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Diagnostic Value of Serum Human Epididymis Protein 4 (HE4) in Ovarian Carcinoma: A Systematic Review and Meta-Analysis
  1. Li Wu, MD*,
  2. Zhi-Yuan Dai, MD,
  3. Yong-Hong Qian, MD,
  4. Yan Shi, MD*,
  5. Feng-Ju Liu, PhD and
  6. Chen Yang, MD*
  1. *Departments of Nuclear Medicine and
  2. Departments of Obstetrics and Gynecology, Affiliated Suzhou Hospital of Nanjing Medical University; and
  3. Departments of Department of Radiation Biology, School of Radiation Medicine and Public Health, Soochow University, Suzhou, Jiangsu Province, PR China.
  1. Address correspondence and reprint requests to Chen Yang, MD, Department of Nuclear Medicine, Affiliated Suzhou Hospital of Nanjing Medical University, 26 Daoqian Rd, Canglang Area, Suzhou, 215002 China. E-mail: 15950093311{at}


Objective Human epididymis protein 4 (HE4), a precursor of human epididymis protein, has been recently identified as a new promising serum biomarker for ovarian carcinoma. We performed a systematic review of studies that investigated the use of HE4 in the diagnosis of ovarian cancer in patients with pelvic or gynecological masses. We also evaluated the diagnostic performance of HE4 for differentiating between patients with benign gynecological disease and those with ovarian cancer.

Methods We searched PubMed database (1990–2011) 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 quality assessment of diagnostic accuracy studies tool. The data were analyzed using Meta-Disc1.4 software. Meta-analysis of the reported sensitivity and specificity of each study and summary receiver operating characteristic (SROC) curve were performed.

Results A total of 9 studies involving 1807 women were included. When the control group was composed of healthy women, the pooled sensitivity and specificity for HE4 in diagnosing ovarian cancer were 83% (95% confidence interval [CI], 77%–88%) and 90% (95% CI, 87%–92%), respectively. The area under the SROC curve was 0.9271. When the control group was composed of women with benign disease, the pooled sensitivity and specificity for HE4 were 74% (95% CI, 69%–78%) and 90% (95% CI, 87%–92%). The area under the SROC curve was 0.8853.

Conclusion The current analysis indicated that HE4 may be a valuable marker in the diagnosis of ovarian carcinoma. Serum HE4 detection is not only a useful preoperative test for predicting the benign or malignant nature of pelvic masses but has a potential to be used as an initial step in ovarian cancer screening strategy.

  • Human epididymis protein 4
  • HE4
  • Tumor marker
  • Ovarian carcinoma
  • Meta-analysis

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  • The authors declare no conflicts of interest.