Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer

J Clin Lab Anal. 2019 Jan;33(1):e22624. doi: 10.1002/jcla.22624. Epub 2018 Jul 15.


Objective: We evaluated the diagnostic performance of CA 125, HE4, and ROMA for ovarian cancer in Koreans and set optimal cutoffs.

Method: Serum levels of HE4 and CA 125 and the ROMA score were determined in 762 patients with benign gynecological disease and 70 with ovarian cancer. Receiver operating characteristic curves were constructed to calculate the areas under the curve (AUC). CA 125, HE4, and ROMA exhibiting maximum Youden index were determined, respectively, as the optimal cutoffs, and sensitivity and specificity were evaluated by applying those cutoffs.

Results: In benign diseases, CA 125 significantly increased in patients with uterine myoma, adenomyosis, endometrial pathology, or endometriosis, but HE4 only increased in patients with adenomyosis. For the diagnosis of ovarian cancer, the combination of CA 125, HE4, and age showed the highest AUC value of 0.892 in the premenopausal group, and ROMA demonstrated the best diagnostic performance, with an AUC of 0.935 in postmenopausal patients. When the optimal cutoff values for CA 125 and HE4 were applied, the sensitivities of CA 125, HE4, and ROMA in premenopausal women were all the same at 0.714, while the specificities were 0.841, 0.974, and 0.972, respectively. In the postmenopausal group, the sensitivities of these markers were 0.857, 0.804, and 0.929, and the specificities were 0.836, 0.887, and 0.800, respectively.

Conclusion: Although all markers demonstrated good diagnostic performance, they varied depending on the pathologic types of benign diseases and ovarian cancer. For accurate diagnosis of ovarian cancer, CA 125, HE4, and ROMA should be used complementarily.

Keywords: ROMA; CA 125; HE4; ovarian cancer; tumor marker.

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Biomarkers, Tumor / blood
  • CA-125 Antigen / blood*
  • Female
  • Humans
  • Menopause
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / pathology
  • Proteins / analysis*
  • Risk
  • Sensitivity and Specificity
  • WAP Four-Disulfide Core Domain Protein 2


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