Human epididymis protein 4 (HE4) is a protein that is produced by most, but not all, epithelial ovarian cancer cells. This makes the test useful as a tumour marker in specific circumstances. The HE4 test measures the amount of human epididymis protein 4 in the blood. Significantly elevated concentrations of HE4 are frequently present in the blood of a woman who has epithelial ovarian cancer. When HE4 is increased, the HE4 test may be used to monitor the effectiveness of treatment and/or for recurrence or progression of the cancer.

Ovarian cancer is the fifth most common cause of cancer death in women. According to the American Cancer Society (ACS), the lifetime risk of a woman developing ovarian cancer is about 1 in 75 and the lifetime risk of death is 1 in 100. ACS estimates that about 22,000 new cases are diagnosed each year in the U.S. and about 14,000 women die of it. Epithelial ovarian cancer is the most common type of ovarian cancer. It originates in cells that cover the outside of the ovaries and accounts for 85% to 90% of ovarian cancers.

There are several different subtypes of epithelial ovarian cancer, including: serous, endometrioid, mucinous, and clear cell, with serous being the most common. Some studies have shown that HE4 is elevated in more than 90% of serous and endometrioid epithelial ovarian cancers and about 50% of clear cell tumours, but it is not usually elevated in mucinous cancers. Therefore, HE4 is not used for monitoring of patients with other types of ovarian cancer, such as mucinous or germ cell tumours.

Currently, there is no reliable method for early detection of ovarian cancer among asymptomatic women. Less than 20% of ovarian cancers are found in the early stages before they have spread outside the ovary. One reason they go undetected is that the symptoms of ovarian cancer are fairly non-specific. The need for a reliable method for early detection of ovarian cancer among asymptomatic women continues to drive ongoing research. In the meantime, regular physicals, pelvic exams, and an awareness of family history and symptoms are important.