The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass

Gynecol Oncol. 2013 Feb;128(2):239-44. doi: 10.1016/j.ygyno.2012.09.034. Epub 2012 Oct 10.


Objective: The purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malignant pelvis masses in Asian women.

Methods: This was a prospective, multicenter (n=6) study with patients from six Asian countries. Patients had a pelvic mass on imaging and were scheduled to undergo surgery. Serum CA125 and HE4 were measured on preoperative samples. CA125, HE4, and ROMA were evaluated for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Results: A total of 414 women with an adnexal mass were evaluated, of which 65 had epithelial ovarian (EOC) cancer, 16 had borderline tumors and 11 had other malignant diseases. Compared to CA125, HE4 had lower sensitivity (56.9% vs 90.8%) and NPV (91.8% vs 97.3%), but improved specificity (96.9% vs 67.1%) and PPV (78.7% vs 35.8%) for differentiating between benign pelvic mass and EOC. ROMA had similar sensitivity (89.2% vs 90.8%) and NPV (97.6% vs 97.3%) as CA125, but showed improved specificity (87.3% vs 67.1%) and PPV (58.6% vs 35.8%). ROMA accurately predicted 87.3% of benign cases as low risk, and 82.6% of stage I/II EOC and 89.2% of all EOC as high risk.

Conclusion: ROMA showed similar sensitivity as CA125 but improved specificity and PPV, especially in premenopausal women. Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood
  • Carcinoma, Ovarian Epithelial
  • Female
  • Humans
  • Membrane Proteins / blood
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / surgery
  • Ovarian Diseases / blood
  • Ovarian Diseases / pathology
  • Ovarian Diseases / surgery
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery
  • Predictive Value of Tests
  • Prospective Studies
  • Proteins / metabolism*
  • ROC Curve
  • WAP Four-Disulfide Core Domain Protein 2


  • Biomarkers, Tumor
  • CA-125 Antigen
  • MUC16 protein, human
  • Membrane Proteins
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human