HE4 (human epididymis protein 4)
A tumour marker used together with CA-125 to estimate the risk that an ovarian mass is cancer. Its advantage is that, unlike CA-125, it is not raised by common benign conditions such as endometriosis and fibroids, making the pair more reliable.
What it measures
HE4 is a protein produced by some ovarian cancers. It is not used alone or as a screening test for healthy women; its established role is in the assessment of a known ovarian mass, where it is combined with CA-125 in a calculation (the ROMA score, which also factors in menopausal status) to estimate how likely the mass is to be cancer versus benign. This helps decide whether a woman should be referred to a specialist cancer centre. HE4's particular value is its specificity: CA-125 is often raised by common benign gynaecological conditions — endometriosis, fibroids, pelvic infection, even menstruation — which can cause false alarms, whereas HE4 is much less affected by these, so using the two together improves accuracy. HE4 can, however, be raised by kidney impairment and by smoking, and in some non-ovarian cancers, so it too is interpreted in context.
What a high value can mean
- Ovarian cancer — the main clinical use; a raised HE4 with CA-125 (in the ROMA score) increases the estimated risk that an ovarian mass is malignant.
- Kidney impairment — can raise HE4 independently of cancer.
- Smoking — modestly raises it.
- Some other cancers (e.g. lung, endometrial) — less commonly. Unlike CA-125, it is usually NOT raised by endometriosis, fibroids or menstruation.
What a low value can mean
- Lower estimated risk of ovarian cancer — a low HE4, with a low CA-125, is reassuring in the assessment of an ovarian mass.
- Normal in health — expected; but HE4 is not used to screen healthy women.
When to discuss with a doctor
HE4 is a specialist tool for characterising an ovarian mass that has already been found, not a screening test to 'check for ovarian cancer' in a woman with no symptoms or mass. Used with CA-125 and menopausal status in the ROMA score, it helps decide the level of cancer risk and whether referral to a gynaecological cancer centre is warranted. A raised result is interpreted alongside imaging and the clinical picture, and can have benign explanations such as kidney impairment. Mediora.AI shows HE4 alongside CA-125 and the other tumour markers so it is read in context; the ovarian-mass assessment and any ROMA calculation belong with your gynaecologist.