ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2012
Interpretation of single and serial measures of HE4 and CA125 in asymptomatic women at high risk for ovarian cancer.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2014Trial
- HE4: a potential diagnostic biomarker in autoimmune diseases.Central-European journal of immunology · 2026Review
- A Parametric Empirical Bayes Approach to Personalized Reference Intervals and Reference Change Values.Clinical chemistry · 2025Article
- Influences of age and sex on the diagnostic accuracy of human epididymis secretory protein 4 for malignant pleural effusion.Scientific reports · 2025Article
- Role of Proteins in Oncology: Advances in Cancer Diagnosis, Prognosis, and Targeted Therapy-A Narrative Review.Journal of clinical medicine · 2024Review
- The High Sensitivity of the Multi-Cancer Detection Test ONCOVERYX-F Offers a Promising Platform for Ovarian Cancer Screening.International journal of women's health · 2024Article
- Clinicopathological characteristics, molecular features and novel diagnostic strategies for the detection of malignant transformation of endometriosis (Review).Experimental and therapeutic medicine · 2023Review
- Article
- Current clinical application of serum biomarkers to detect and monitor ovarian cancer - update.Przeglad menopauzalny = Menopause review · 2021Review
- HE4 might be a more useful tumor biomarker to detect malignancy in patients with ovarian endometrioma when malignancy is suspected.The Journal of international medical research · 2021Article
- Comparison of two immunoassays for the measurement of serum HE4 for ovarian cancer.Practical laboratory medicine · 2021Article
- Epidemiologic and biologic correlates of serum HE4 and CA125 in women from the National Health and Nutritional Survey (NHANES).Gynecologic oncology · 2021Article
- Diagnostic Performance of F-18 FDG PET/CT Compared with CA125, HE4, and ROMA for Epithelial Ovarian Cancer.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Serum Human Epididymis Protein 4 is a Potential Biomarker for Early Chronic Kidney Disease in an Obese Population.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- CA125 and Ovarian Cancer: A Comprehensive Review.Cancers · 2020Review
- [Comparison of serum cancer antigen 125, human epididymis protein 4, ROMA, and CPH-I for diagnosis of ovarian cancer in Chinese patients with ovarian mass].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review.Journal of ovarian research · 2019Review
- Does the Risk of Ovarian Malignancy Algorithm Provide Better Diagnostic Performance Than HE4 and CA125 in the Presurgical Differentiation of Adnexal Tumors in Polish Women?Disease markers · 2018Article
- Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort.Journal of ovarian research · 2017Article
- HE4 Serum Levels in Patients with BRCA1 Gene Mutation Undergoing Prophylactic Surgery as well as in Other Benign and Malignant Gynecological Diseases.Disease markers · 2017Article
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundHuman epididymis protein 4 (HE4) is approved for clinical use with CA125 to predict epithelial ovarian cancer in women with a pelvic mass or in remission after chemotherapy. Previously reported reference ranges for HE4 are inconsistent.
methodsWe report positivity thresholds yielding 90%, 95%, 98%, and 99% specificity for age-defined populations of healthy women for HE4, CA125, and Risk of Ovarian Malignancy Algorithm (ROMA), a weighted average of HE4 and CA125. HE4 and CA125 were measured in 1,780 samples from 778 healthy women aged >25 years with a documented deleterious mutation, or aged >35 years with a significant family history. Effects on marker levels of a woman's age, ethnicity, and epidemiologic characteristics were estimated, as were the population-specific means, variances, and within- and between-woman variances used to generate longitudinal screening algorithms for these markers.
resultsCA125 levels were lower with Black ethnicity (P = 0.008). Smoking was associated with higher HE4 (P = 0.007) and ROMA (P < 0.019). Continuous oral contraceptive use decreased levels of CA125 (P = 0.041), and ROMA (P = 0.12). CA125 was lower in women age ≥55, and HE4 increased with age (P < 0.01), particularly among women age ≥55.
conclusionsBecause of the strong effect of age on HE4, thresholds for HE4 are best defined for women of specific ages. Age-specific population thresholds for HE4 for 95% specificity ranged from 41.4 pmol/L for women age 30 to 82.1 pmol/L for women age 80. IMPACT: Incorporation of serial marker values from screening history reduces personalized thresholds for CA125 and HE4 but is inappropriate for ROMA.
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