Role of HE4 in evaluation of adnexal masses - comparison with CA125, ROMA and RMI in premenopausal women

Sep 21, 2026

Ovarian cancer ranks among the most prevalent gynecologic malignancies, and reliable screening using tumour markers or ultrasonography remains unestablished. This observational cross-sectional study assessed HE4 as a biomarker for ovarian malignancies in 100 premenopausal women with ovarian masses, alone and within diagnostic algorithms. Diagnostic performance of CA125, HE4, ROMA scores, and RMI was analyzed against postoperative histopathology, using ROC measures.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Ovarian cancer burden and screening challenges

CA125 limitations in premenopausal women

Role of HE4 and diagnostic algorithms

Methods

Role of HE4 in evaluation of adnexal masses and its comparison with CA125, ROMA and RMI in premenopausal women Mini Sharma1, Neeraj Kumar2, Subhas Saha1, Vanita Suri1, GR Prasad1, Radhika Srinivasan3, Arnab Pal4 1. Post Graduate Institute of Medical Education and Research, OBG. 2. Dr Rajendra Prasad Government Medical College. 3. Postgraduate Institute of Medical Education and Research, Chandigarh, Cytology and Gynecological Pathology. 4. Post Graduate Institute of Medical Education and Research, Biochemistry. Abstract Background: Ovarian cancer is the seventh most common cancer in women and is ranked third among gynaecological malignancies after cervical and uterine cancers. Prospective studies have failed to establish a definite screening programme based on tumour markers or ultrasonography. Objective: To evaluate potential role of Human Epididymis protein 4 (HE4) as a biomarker for diagnosis of various ovarian malignancies in premenopausal age group, either alone or as a part of diagnostic algorithm like Risk of Malignancy Algorithm (ROMA) and to analyse if it has any advantage over Cancer Antigen 125 (CA125) or Risk of Malignancy Index (RMI) . Methods: It was an observational cross-sectional study which included 100 premenopausal women having ovarian mass and underwent surgery. The diagnostic performances of CA125, HE4, ROMA score and RMI for ovarian cancer were evaluated. Results: Postoperative histopathology confirmed 30%(n=30) women to have malignant ovarian tumors. According to receiver operating characteristic (ROC) analysis; area under curve (AUC) was maximum for ROMA (0.791) followed by HE4 (0.784), RMI (0.750) and CA125 (0.715) . Conclusion: HE4 is not superior to CA125 but, it can be used in series or as part of diagnostic algorithm (ROMA) along with CA125 to get higher diagnostic accuracy for premenopausal women. Keywords: Adnexal mass; CA125; HE4; Ovarian neoplasms; Risk of malignancy index (RMI); Risk of malignancy algorithm (ROMA) . DOI: [https://dx.doi.org/10.4314/ahs.v24i4.16](https://dx.doi.org/10.4314/ahs.v24i4.16) Cite as: Sharma M, Kumar N, Saha S, Suri V, Prasad GR, Srinivasan R, et al. Role of HE4 in evaluation of adnexal masses and its comparison with CA125, ROMA and RMI in premenopausal women. Afri Health Sci. 2024; 24(4). 120-128. [https://dx.doi.org/10.4314/ahs](https://dx.doi.org/10.4314/ahs). v24i4.16 Introduction Ovarian cancer is the seventh most common cancer in women and is ranked third among gynaecological malignancies after cervical and uterine cancers 1. 5 year survival rates are much lower for ovarian cancer compared to other cancers that affect women because 70% of ovarian malignancies are diagnosed in advanced stage 2 3. Prospective studies have failed testablish a definite screening programme based on tumour markers or ultrasonography 4 5. Cytology based screening test cannot be developed for ovarian malignancy due to relative inaccessibility of ova- Corresponding author: Subhas Saha, Post Graduate Institute of Medical Education and Research, OBG. [Email: doc03121986@gmail.com](Email: doc03121986@gmail.com) ries as compared to other pelvic organs and its intraperitoneal location. Transabdominal or transvaginal Fine Needle Aspiration Cytology (FNAC) is described as a potential method but with obvious risk of rupturing an intact capsule and intraperitoneal spread of the malignant cells. Cancer Antigen 125 (CA125) is the most frequently used biomarker for ovarian malignancy having established role in ovarian malignancy in postmenopausal women with high sensitivity and specificity 3. But in premenopausal women it has high false positive rate since it is falsely elevated in some benign ovarian conditions (which are more common in premenopausal age group) and diseases other than those that affect the ovary like first trimester of pregnancy, breast cancer, endometriosis, PID (Pelvic Inflammatory Disease) and other malignancies besides ovarian cancer (brea

FAQs

What was the study objective regarding HE4 in ovarian malignancy?

To evaluate HE4 as a biomarker for diagnosing various ovarian malignancies in premenopausal women, either alone or as part of the ROMA diagnostic algorithm, and to compare its advantage over CA125 and RMI.

How was the study conducted and what was the reference standard?

The study was an observational cross-sectional design including 100 premenopausal women with an ovarian mass who underwent surgery. Diagnostic performance was evaluated against postoperative histopathology.

How did ROMA, HE4, RMI, and CA125 perform for diagnosing ovarian cancer?

ROC analysis showed the highest AUC for ROMA (0.791), followed by HE4 (0.784), RMI (0.750), and CA125 (0.715).

What is the study conclusion about HE4 compared with CA125?

HE4 was not superior to CA125, but it can be used in series or as part of the diagnostic algorithm (ROMA) together with CA125 to improve diagnostic accuracy in premenopausal women.

Sep 21, 2026

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