HE4 and epithelial ovarian cancer : Comparison and clinical evaluation of two immunoassays and a combination algorithm

Background: Two commercial immunoassays for HE4 have been compared and the diagnostic accuracy of HE4,
CA 125 and the combinatory ROMA algorithm for epithelial ovarian cancer (EOC) has been evaluated.
Methods: HE4 and CA125 were measured on sera obtained from 259 women (73 healthy, 90 with benign
ovarian or adnexal diseases, 96 with EOC). The ARCHITECT CMIA HE4 assay was compared with the Fujirebio
EIA HE4, and the risk for EOC by the combinatory ROMA algorithm (HE4+CA 125) was assessed with both
HE4 assays.
Results: The CMIA HE4 assay showed a good linearity (rN0.9998) and precision (interassay and total CVs b4%).
The correlation with EIA HE4 was linear (r=0.994), with an average bias of 0.4%. By ROC curve analysis, the
sensitivity for EOC at a fixed specificity of 90%, 95% and 99% was 89.6%, 84.4% and 79.2% by CMIA HE4, 84.4%,
83.3% and 79.2% by EIA HE4, 86.5%, 76.0% and 59.4% by CMIA CA125. The accuracy of the ROMA algorithm
determined by CMIA or EIA HE4 was very similar (AUC 87.1% vs. 87.6%; p=n.s.) and greater in menopause.
Conclusions: The two HE4 assays showed a good correlation and similar clinical value, with a greater precision
for CMIA. HE4 was more specific and accurate than CA125, supporting its use in addition to clinical and
imaging criteria for the discrimination of benign from malignant ovarian lesions. The ROMA algorithm
showed a good accuracy for discriminating women at high risk for EOC.