Is serum human epididymis protein 4 ready for prime time?

Abstract

The National Institute for Health and Clinical Excellence (NICE) guidelines have sparked hot debate regarding the role of carbohydrate antigen 125 (CA-125) for ovarian cancer (OC) detection. Recent literature and evidence calls into question the use of CA-125 in diagnostic algorithms, given the better performance of human epididymis protein 4 (HE4) vs. CA-125 to rule OC. This is an important consideration since combined measurements are not cost-effective. The quality of this evidence is, however, threatened by important gaps related to study design, enrolled populations and analytical issues. For instance, despite the clinical need to prioritize the evaluation of biomarker performance in early stage tumours, sound evidence on this cannot be provided. In addition, results should be cautiously interpreted due to wide differences in the type of employed assays and in adopted diagnostic thresholds for HE4. Comparability among results obtained by different commercially available HE4 assays, together with an objective establishment of analytical goals is essential for the optimal clinical application of this marker.

Keywords: Commutability; biological variability; biomarker; ovarian cancer; reference change value.