DESCRIPTION
Human epididymis protein 4 (HE4) is a potential new biomarker for detecting ovarian cancer early and for monitoring disease progression and recurrence. It has been cleared by the U.S. Food and Drug Administration (FDA) for monitoring patients with epithelial ovarian cancer. HE4 is proposed as a replacement for or a complement to CA-125, a biomarker with limited specificity.
In June of 2008 the HEA EIA test kit (Fujirebio Diagnostics, Sweden) was cleared by the FDA through the 510(k) process for monitoring patients with epithelial ovarian cancer. HE4 is made up of two whey acidic proteins with a four disulfide core domain. It has been found to be over expressed by epithelial ovarian cancer tumors and to circulate in the serum of patients with epithelial ovarian cancer. Levels of HE4 may be less likely to be elevated due to benign conditions, as is the case with CA-125, which would make it a candidate to replace or complement CA-125. Tests for HE4 are FDA-approved for monitoring women known to have epithelial ovarian cancer. Although HE4 tests are not FDA-approved for evaluating women with ovarian masses to aid in the identification of malignant tumors, these tests have been investigated for this indication and are available outside of the U.S. for evaluating women with pelvic masses. In March of 2010 the ARCHITECT HE4 (Abbott Diagnostics, UK, co-developed with Fujirebio Diagnostics), an automated version of the HE4 EIA test, was cleared by the FDA for the same indications. The ARCHITECT HE4 test is being distributed in the United States by Quest Diagnostics of Madison, NJ.
POLICY
Measurement of HE4 for all conditions/diseases including, but not limited to, the following is considered investigational:
Diagnosing malignant disease in women with signs or symptoms possibly suggestive of ovarian cancer
Monitoring disease progression or recurrence in women diagnosed with epithelial ovarian cancer
Screening asymptomatic women for ovarian cancer
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
There is limited data on the diagnostic test performance of the HE4 test used to monitor disease progression and recurrence in women diagnosed with epithelial ovarian cancer, the FDA-approved indication for the test. The only available data on diagnostic test performance are in FDA documents; the reported studies were small, retrospective, many have included duplicate data on the same women, and used different cut-offs for identifying a recurrence. In general, there is no established cut-off for determining when an HE4 test is positive, whether for identifying disease progression or recurrence or for determining risk of malignancy in prospective studies on the clinical utility of any application of the HE4 test, and no published studies exist on use of the HE4 test to screen asymptomatic women. Thus, the HE4 test is considered investigational for all indications.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (8:2010). Serum biomarker human epididymis protein 4 (HE4) (2.04.66). Retrieved December 29, 2010 from BlueWeb. (11 articles and / or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 4/4/2011
MOST RECENT REVIEW DATE: 4/4/2011
ID_EBA
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