HE4 test explained

HE4 (human epididymis protein 4) is a protein whose level in the blood can rise in epithelial ovarian cancer. Like CA 125, HE4 is classed as a tumour marker — a substance whose level often rises because of cancer, but which can also rise for other reasons. According to MedlinePlus, if a woman has already been treated for ovarian cancer, her doctor may order an HE4 test together with CA 125 to assess whether the treatment is working and whether the disease has come back after treatment ended. The source states that some studies show both markers together give more accurate information than either of them alone. HE4 may also be assessed when a suspicious pelvic mass has been found: together with imaging tests it helps to weigh the likelihood of malignancy before deciding on further steps. HE4 is not intended for ovarian cancer screening in women without symptoms — it is used purposefully, when there is already a diagnosis or a well-founded suspicion.

• To monitor how well treatment is working in already diagnosed ovarian cancer (most often together with CA 125)
• After treatment has ended — to check that HE4 is not rising, which could indicate that the disease has returned
• When a suspicious mass in the pelvis has been found — the likelihood of malignancy is weighed together with CA 125 (the ROMA index) before further steps
• When there are symptoms that raise a suspicion of ovarian disease (bloating, pelvic pain, feeling full quickly, a frequent need to pass urine) — together with imaging tests
• When assessing women at high risk, together with other tests

There is no single international HE4 reference limit: it depends on the method the laboratory uses, and also on the woman's age and menopausal status. You will find the exact interval on your own result sheet, alongside the method that was used. A raised HE4 is not in itself a diagnosis, so further tests are needed to make sense of it.

A raised HE4

A raised HE4 is most often assessed in the context of ovarian cancer that has already been diagnosed or is suspected — it may indicate that treatment is not working well enough, or that the disease has possibly returned after treatment ended. A raised HE4 is also taken into account when the likelihood of malignancy is being weighed after a pelvic mass has been found. A raised HE4 on its own proves nothing, so further tests are needed.

• Epithelial ovarian cancer that is not responding well enough to treatment, or that has recurred after treatment ended
• A suspicious mass in the pelvis, when the likelihood of malignancy is weighed together with CA 125 (the ROMA index) before further steps

Symptoms that may go with a raised HE4

• Bloating or an enlarged abdomen
• Pain or tenderness in the lower abdomen or the pelvis
• Feeling full quickly or a loss of appetite
• A frequent or urgent need to pass urine
• Tiredness
• Weight loss with no clear cause

What a doctor usually assesses next

• Whether HE4 is rising or falling over the course of treatment, rather than a single value
• CA 125 assessed alongside it and the ROMA index calculated, especially when a mass in the pelvis has been found
• Additional imaging tests (ultrasound and others)
• Whether the symptoms (bloating, pain, feeling full quickly, frequent passing of urine) last longer than a few weeks

HE4, CA 125 and the ROMA index

Both HE4 and CA 125 are ovarian cancer markers, but they are different proteins. According to MedlinePlus, some studies show that HE4 and CA 125 assessed together give more accurate information than either marker on its own about whether treatment is working and whether the disease has come back after treatment. The ROMA index (Risk of Ovarian Malignancy Algorithm) is calculated from the HE4 and CA 125 values and the woman's menopausal status, in order to assess the likelihood of malignancy when a mass in the pelvis has been found. The exact value and how to interpret it are explained by a doctor.

Screening and the cost of an HE4 test

Like CA 125, HE4 is not used, according to the sources available, as a screening test in women without symptoms — both markers are used purposefully, when there is already a diagnosis or a well-founded suspicion. No fixed price was found in publicly published sources: the cost depends on the laboratory. Unlike the PSA test or the faecal occult blood (iFOBT) test, HE4 is not included in any state-funded early diagnosis programme, so it cannot be obtained free of charge under a screening programme. Related pages: bowel cancer screening in Lithuania, how to prepare for a blood test and how to read blood test results.