Human epididymis protein 4 (HE4) is a novel biomarker that has been proposed as a replacement for or a complement to carbohydrate antigen 125 (CA-125) for monitoring ovarian cancer progression and recurrence. HE4 is also proposed as a test to evaluate women with ovarian masses and to screen for ovarian cancer in asymptomatic women.
There are limited data on the diagnostic test performance of the HE4 test used to monitor disease progression and recurrence in women after initial treatment for epithelial ovarian cancer. There is no established cutoff for determining when an HE4 test is positive or for identifying disease progression or recurrence. Moreover, a survival advantage of early detection of ovarian cancer recurrence using HE4 levels has not been established.
Measurement of HE4 for all indications is considered investigational.
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Studies have not found that HE4 improves diagnostic accuracy beyond that of subjective assessment of transvaginal ultrasound. The evidence is insufficient to conclude that HE4 alone or in combination with CA-125 has better diagnostic performance than CA-125 alone. No published studies were identified evaluating use of the HE4 test to screen asymptomatic women for ovarian cancer.
BlueCross BlueShield Association. Evidence Positioning System. (1:2019). Serum biomarker human epididymis protein 4 (2.04.66). Retrieved August 19, 2019 from https://www.evidencepositioningsystem.com/. (26 articles and / or guidelines reviewed)
Gentry-Maharah, A., Burnell, Matthew.,Dilley, J., Ryan, A., Karpinskyj, C., Gunu, R., et al. (2019). Serum HE4 and diagnosis of ovarian cancer in postmenopausal women with adnexal masses. American Journal of Obstetrics and Gynecology, 9378 (19) 30936-6. (Level 2 evidence)
Karlsen, N., Karlsen, M., Høgdall, C., & Høgdall, E. (2014) HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors: a systematic review. Cancer Epidemiology Biomarkers and Prevention, 23 (11), 2285-95. (Level 1 evidence)
Lakshmanan, M., Kumar, V., Chaturvedi, A., Misra, S., Gupta, S., Akhtar, N., Rajan, et al. (2019). Role of Serum HE4 as a prognostic marker in carcinoma of the ovary. Indian Journal of Cancer, 56 (3), 216-221. Abstract retrieved August 19, 2019 from PubMed database.
National Comprehensive Cancer Network. (2019, March). NCCN clinical practice guidelines in oncology (NCCN guidelines®) Ovarian cancer. V.1.2019. Retrieved August 19, 2019 from the National Comprehensive Cancer Network.
Scaletta, G., Plotti, F., Luvero, D., Capriglione, S., Montera, R., Miranda, A., et al. (2017). The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: a systematic review. Expert Review of Anticancer Therapy, 17 (9), 827-839. Abstract retrieved August 14, 2017 from PubMed database.
Steffensen, K., Waldstrøm, M., Brandslund, I., Lund, B., Sørensen, S., Petzold, M., & Jakobsen, A. (2016). Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer. Oncology Letters, 11, 3967-3974. (Level 3 evidence)
U. S. Food and Drug Administration. (2008, June). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K072939. Retrieved August 14, 2017 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (2010, March). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K093957. Retrieved March 18, 2014 from http://www.accessdata.fda.gov.
U.S. Preventive Services Task Force. (2018). Screening for ovarian cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Journal of the American Medical Association, 319 (6), 588-594.
Zhen, S., Bian, L., Chang, L., & Gao, X. (2014). Comparison or serum human epididymis protein 4 and carbohydrate antigen 125 as markers in ovarian cancer: a meta-analysis. Molecular and Clinical Oncology, 2, 559-566. (Level 1 evidence)
ORIGINAL EFFECTIVE DATE: 4/4/2011
MOST RECENT REVIEW DATE: 10/10/2019
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