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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi

CiteScore 2018: 2.43

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Source Normalized Impact per Paper (SNIP) 2018: 0.837

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Volume 35, Issue 1


Evaluation in the predictive value of serum human epididymal protein 4 (HE4), cancer antigen 125 (CA 125) and a combination of both in detecting ovarian malignancy

Beng Hock Teh / Soon Leong YongORCID iD: http://orcid.org/0000-0003-2836-0756 / Wee Wee Sim / Kim Bee Lau / Haris Njoo Suharjono
Published Online: 2018-07-31 | DOI: https://doi.org/10.1515/hmbci-2018-0029



This study was conducted to evaluate the performance of human epididymal protein 4 (HE4), cancer antigen 125 (CA 125) and a combination of both via the Risk of Ovarian Malignancy Algorithm (ROMA) in detecting ovarian malignancy.


This was a diagnostic study enrolling 129 patients with pelvic mass(es) suspected of originating in the ovary who had been scheduled for surgery or radiological-guided biopsy. Serum HE4 and CA 125 levels were measured. HE4, CA 125 and ROMA were evaluated for sensitivity, specificity, positive predictive value and negative predictive value. The receiver operating characteristic (ROC) plots were graphed and area under the curve (AUC) values were calculated to investigate the accuracy of each marker for predicting ovarian malignancy.


Overall, CA 125 remained significantly more sensitive (88.9% vs. 51.9%, p = 0.006) but less specific (56.9% vs. 95.1%, p < 0.001) than HE4. HE4 was superior to CA 125 in specificity (97.7% vs. 54.5%, p < 0.001) for premenopausal women. ROMA was non-significantly more sensitive (100.0% vs. 92.3%, p = 1.000) than CA 125 but both were equally specific (71.4%) for the postmenopausal group. In the premenopausal group, the AUC of serum HE4 was higher than serum CA 125 (0.851 vs. 0.817) but was equivalent to ROMA (0.851 vs. 0.859). In the postmenopausal group, ROMA exhibited an excellent AUC value as compared to CA 125 and HE4 (AUC of 0.907 vs. 0.874 vs. 0.863, respectively).


HE4 is useful in ruling out ovarian malignancy among premenopausal women. For postmenopausal women, ROMA appears to be an all-rounder with overall good sensitivity and specificity.

Keywords: CA 125; HE4; ovarian cancer; pelvic mass; ROMA


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About the article

Received: 2018-04-29

Accepted: 2018-06-19

Published Online: 2018-07-31

Author Statement

Research funding: This was a self-funded research using department’s own source of funds. No grant number applied.

Conflict of interest: The authors declare that they have no conflicts of interest. Roche Diagnostics (Malaysia) Sdn. Bhd. provided the Elecsys HE4 and CA 125 II reagent kits for the purpose of this research project. However, the company had no involvement or input in the study design, data collection, statistical analysis, data interpretation or preparation of manuscript. None of the authors received any form of personal gifts or compensation from Roche Diagnostics (Malaysia) Sdn. Bhd.

Informed consent: Informed consent has been obtained from all participants.

Ethical approval: The research related to human use complies with all the relevant national regulations and institutional policies, was performed in accordance with the tenets of the Helsinki Declaration. This study had been registered to National Medical Research Register (under Ministry of Health Malaysia) and ethical approval for this research was obtained from Medical Research and Ethics Committee, Ministry of Health Malaysia. The Research Identification Number given was NMRR-13-380-15355.

Submission declaration: This study had been presented at the 5th Scientific Meeting of Obstetrics and Gynaecology UKM Medical Centre and the 24th Congress of the Obstetrical and Gynaecological Society of Malaysia on 9th April 2016 and 3rd June 2016, respectively.

Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 35, Issue 1, 20180029, ISSN (Online) 1868-1891, DOI: https://doi.org/10.1515/hmbci-2018-0029.

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