A predictive model combining human epididymal protein 4 and radiologic features for the diagnosis of ovarian cancer

Gynecol Oncol. 2014 Mar;132(3):573-7. doi: 10.1016/j.ygyno.2014.01.005. Epub 2014 Jan 10.


Objective: Ovarian cancer is the leading cause of death in women with gynecologic cancer. CA125 is the commonly used biomarker in the diagnosis of ovarian cancer, but has limitations in both sensitivity and specificity. Human Epididymal secretory protein (HE4) is a promising biomarker and is included in the Risk of Ovarian Malignancy Algorithm (ROMA) score, which is suggested to further increase the diagnostic accuracy than either marker alone. However, information from ultrasound and CT-scan is not included in this algorithm. This study evaluated the diagnostic accuracy of HE4 in the pre-operative diagnosis of ovarian cancer and the predictive values of biomarkers, ultrasound and CT-scan and combinations hereof.

Methods: HE4 and CA125 were measured in 361 subjects (34 benign, 147 ovarian cancer and 180 controls). Sensitivity, specificity and area under the curve (AUC) for CA125, HE4, ROMA and RMI scores were calculated using the receiver operating characteristic (ROC) methodology. The additional predictive value of ultrasound or CT-scan to the individual markers was analyzed using logistic regression.

Results: The sensitivity in predicting ovarian cancer of CA125 was 91% and of HE4 90%. The specificity was 65% and 97% respectively. HE4 demonstrated the highest discrimination (ROC-AUC=0.96), compared to ROMA, RMI and CA125 (AUC=0.95, 0.89 and 0.90 respectively). ROMA did not improve when it was combined with different ultrasound factors. The presence of intra-abdominal metastasis on CT-scan improved the discriminative potential of HE4 (p=0.0004).

Conclusion: HE4 in combination with CT-scan may be incorporated in the diagnostic work-up in women with a pelvic mass.

Keywords: CT-scan; HE4; Ovarian cancer; RMI; Ultrasound.

Publication types

  • Observational Study

MeSH terms

  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood
  • Carcinoma, Ovarian Epithelial
  • Female
  • Humans
  • Logistic Models
  • Membrane Proteins / blood
  • Middle Aged
  • Models, Statistical*
  • Multivariate Analysis
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / diagnostic imaging*
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / diagnostic imaging*
  • Predictive Value of Tests
  • Proteins / analysis*
  • Retrospective Studies
  • Tomography, X-Ray Computed
  • Ultrasonography
  • 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