AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO026340435
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ORIGINAL RESEARCH ARTICLE

Diagnostic performance of human epididymis protein 4 in predicting occult endometrial carcinoma among women with endometrial intraepithelial neoplasia

Aysel Mammadova1* ,  Gulnara Jafarova1
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1 Department of Oncology, Oncology Clinic, Azerbaijan Medical University, Baku , Azerbaijan
EJMO, 026340435 https://doi.org/10.36922/EJMO026340435
Received: 18 August 2026 | Revised: 12 September 2026 | Accepted: 23 September 2026 | Published online: 22 October 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Endometrial intraepithelial neoplasia (EIN) carries a substantial risk of concurrent occult endometrial carcinoma. Accurate preoperative risk assessment is important for appropriate surgical planning

Objective: To assess the diagnostic accuracy of serum human epididymis protein 4 (HE4) in identifying occult endometrial carcinoma in women with EIN, compare its performance with cancer antigen 125 (CA-125) and the Risk of Ovarian Malignancy Algorithm (ROMA) index, and assess the value of integrating clinical, ultrasonographic, histopathological, and biomarker variables into a preoperative prediction model.

Methods: This retrospective study included 113 women with histologically confirmed EIN who underwent hysterectomy between 2019 and 2025. Clinical, ultrasonographic, histopathological, and biomarker data, including serum CA-125, HE4, and ROMA, were evaluated. Diagnostic performance was assessed using receiver operating characteristic analysis, and independent predictors were identified by multivariable logistic regression.

Results: Occult endometrial carcinoma was identified in 46/113 women (40.7%). Malignant postoperative findings were associated with age > 50 years, obesity, postmenopausal status, endometrial thickness >10 mm, and high-risk preoperative histopathology. HE4 showed the highest diagnostic performance (area under the curve [AUC] = 0.912; 95% confidence interval [CI]: 0.832–0.961; p < 0.001), compared with ROMA (AUC = 0.846) and CA-125 (AUC = 0.563). High-risk preoperative histopathology (odds ratio = 31.85; 95% CI: 8.71–116.42; p < 0.001) and HE4 (OR = 4.53 per 50 pmol/L increase; 95% CI: 1.86–11.02; p = 0.001) were independent predictors. The final model demonstrated excellent discrimination (AUC = 0.951), with 84.8% sensitivity, 97.0% specificity, and 92.0% accuracy.

Conclusion: HE4 outperformed CA-125 and ROMA and remained an independent predictor of occult carcinoma. Integrating HE4 with clinicopathological variables may improve preoperative risk stratification and surgical decision-making in women with EIN.

Graphical abstract
Keywords
Endometrial intraepithelial neoplasia
Occult endometrial carcinoma
Human epididymis protein 4
Cancer antigen 125
Risk of Ovarian Malignancy Algorithm index
Logistic regression
Risk prediction
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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