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

A. Stiekema, C. A.R. Lok, G. G. Kenter, W. J. Van Driel, Andrew Vincent, C. M. Korse

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21 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)573-577
Number of pages5
JournalGynecologic Oncology
Issue number3
Publication statusPublished or Issued - 1 Jan 2014
Externally publishedYes


  • CT-scan
  • HE4
  • Ovarian cancer
  • RMI
  • Ultrasound

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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