Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and CA125 in predicting epithelial ovarian cancer: a meta-analysis

BMC Cancer. 2012 Jun 19;12:258. doi: 10.1186/1471-2407-12-258.


Backgrounds: Risk for Ovarian Malignancy Algorithm (ROMA) and Human epididymis protein 4 (HE4) appear to be promising predictors for epithelial ovarian cancer (EOC), however, conflicting results exist in the diagnostic performance comparison among ROMA, HE4 and CA125.

Methods: Remote databases (MEDLINE/PUBMED, EMBASE, Web of Science, Google Scholar, the Cochrane Library and and full texts bibliography were searched for relevant abstracts. All studies included were closely assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). EOC predictive value of ROMA was systematically evaluated, and comparison among the predictive performances of ROMA, HE4 and CA125 were conducted within the same population. Sensitivity, specificity, DOR (diagnostic odds ratio), LR ± (positive and negative likelihood ratio) and AUC (area under receiver operating characteristic-curve) were summarized with a bivariate model. Subgroup analysis and sensitivity analysis were used to explore the heterogeneity.

Results: Data of 7792 tests were retrieved from 11 studies. The overall estimates of ROMA for EOC predicting were: sensitivity (0.89, 95% CI 0.84-0.93), specificity (0.83, 95% CI 0.77-0.88), and AUC (0.93, 95% CI 0.90-0.95). Comparison of EOC predictive value between HE4 and CA125 found, specificity: HE4 (0.93, 95% CI 0.87-0.96) > CA125 (0.84, 95% CI 0.76-0.90); AUC: CA125 (0.88, 95% CI 0.85-0.91) > HE4 (0.82, 95% CI 0.78-0.85). Comparison of OC predictive value between HE4 and CA125 found, AUC: CA125 (0.89, 95% CI 0.85-0.91) > HE4 (0.79, 95% CI 0.76-0.83). Comparison among the three tests for EOC prediction found, sensitivity: ROMA (0.86, 95%CI 0.81-0.91) > HE4 (0.80, 95% CI 0.73-0.85); specificity: HE4 (0.94, 95% CI 0.90-0.96) > ROMA (0.84, 95% CI 0.79-0.88) > CA125 (0.78, 95%CI 0.73-0.83).

Conclusions: ROMA is helpful for distinguishing epithelial ovarian cancer from benign pelvic mass. HE4 is not better than CA125 either for EOC or OC prediction. ROMA is promising predictors of epithelial ovarian cancer to replace CA125, but its utilization requires further exploration.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Biomarkers, Tumor / metabolism*
  • CA-125 Antigen / metabolism*
  • Carcinoma, Ovarian Epithelial
  • Female
  • Humans
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / metabolism
  • Prognosis
  • Proteins / metabolism*
  • Quality Control
  • ROC Curve
  • Reproducibility of Results
  • WAP Four-Disulfide Core Domain Protein 2


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