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Human Epididymis Protein 4: A Prognostic Tool for Epithelial Ovarian Cancer

8 February 2013


Background: Human epididymis protein 4 (HE4) also referred to as whey acidic protein (WAP) is a promising and heavily studied biomarker for ovarian cancer. A systematic review of studies evaluating the prognostic significance of pretreatment HE4 in women with epithelial ovarian cancer was performed.

Methods: An exhaustive search of medical literature using Medline-OVID, Web of Science, CINAHL and Google Scholar was performed. The search was limited to year 2000 to 2013, human subjects and the English language. Each study was appraised and quality was assessed using the GRADE criteria.

Results: A total of five observational studies were included. One study evaluated the prognostic value of HE4 for progression-free survival (PFS), disease-free survival (DFS) and overall survival (OS), while two studies only evaluated for PFS. The remaining studies evaluated for both PFS and OS. Of the four studies that evaluated for PFS, three studies showed that a higher preoperative serum HE4 level is significantly associated with shorter PFS. However, the remaining study showed no association between preoperative serum HE4 level and PFS. The three studies that evaluated for OS, all showed significant association between high preoperative HE4 levels and shorter OS. One study for DFS showed similar correlation of having high HE4 levels and increased frequency of relapse.

Conclusion: Based on the current analysis, HE4 can be considered a valuable biomarker in assessing the prognosis of women with ovarian cancer prior to receiving primary treatment. This test can also help in identifying women who will benefit with more aggressive treatment. A weak recommendation is made in the use of HE4 test because majority of the studies had small sample sizes and were performed in single sites, thus making it difficult to generalize the results. A large, multi-center prospective study would validate the findings of this review.


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