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Ovarian Cancer

HE4 Test - Ovarian Cancer Biomarker

The HE4 test measures levels of the HE4 protein to help detect and monitor epithelial ovarian cancer and to assess whether a pelvic mass is more likely benign or malignant. Used alongside CA‑125 and risk algorithms, it may help catch ovarian cancer earlier or spot recurrence sooner, enabling timelier treatment and potentially reducing the chance of advanced‑stage disease.

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Key Insights

  • Understand how this test detects signals tied to ovarian cancer—helping reveal whether tumor‑related proteins are present at higher‑than‑expected levels.
  • Identify a biomarker (HE4) that can help explain concerning findings like an adnexal mass on ultrasound, persistent bloating, or rising tumor markers.
  • Learn how age, menopausal status, kidney function, smoking, and tumor subtype can influence your HE4 result and its meaning.
  • Use insights to guide next steps with your clinician, such as combining HE4 with CA‑125, imaging, or the ROMA score to refine cancer risk assessment and treatment planning.
  • Track how your levels change over time to monitor response after surgery or chemotherapy and to watch for possible recurrence.
  • When appropriate, integrate this test’s findings with related panels—like CA‑125, inflammatory markers, and imaging—to build a more complete picture of ovarian health.

What Is a HE4 Test?

The HE4 test measures human epididymis protein 4 (gene: WFDC2) in your blood. HE4 is a protein commonly overproduced by epithelial ovarian cancers, especially serous and endometrioid subtypes. The test is typically performed on a serum sample using validated immunoassays (for example, chemiluminescent methods) designed to detect very small amounts with high specificity. Results are reported as a concentration (often in pmol/L) and interpreted against reference intervals that vary by laboratory method and by menopausal status.

This matters because HE4 behaves as a tumor biomarker: higher levels can reflect tumor activity, tumor burden, or recurrence risk. In practice, clinicians often pair HE4 with CA‑125 and imaging to stratify the likelihood that an ovarian mass is malignant and to monitor treatment response. While no single biomarker can “diagnose cancer,” adding objective HE4 data can uncover risk that isn’t obvious from symptoms alone and can help time-sensitive decisions—like referral to a gynecologic oncologist—happen sooner.

Why Is It Important to Test Your HE4?

Ovarian cancer can be quiet early on, but at the cellular level many tumors shed proteins that seep into the bloodstream. HE4 is one of those signals. Testing can reveal a pattern of overexpression linked to epithelial ovarian cancer, offering a biochemical readout that complements what clinicians see on ultrasound or CT. HE4 is also less affected than CA‑125 by benign conditions such as endometriosis, which can improve specificity when you’re trying to sort out an indeterminate adnexal mass. It is particularly relevant when imaging finds a complex ovarian cyst, when symptoms raise concern (like persistent abdominal fullness), and throughout treatment to gauge response.

Zooming out, HE4 supports prevention and outcomes by turning guesses into trend lines. Regular, targeted testing in the right clinical context helps detect early changes, track how surgery or chemotherapy is working, and flag potential recurrence sooner. The aim is not to “pass or fail” a single number, but to see where your biology stands and how it adapts over time—so your care team can match the intensity of care to the level of risk.

What Insights Will I Get From a HE4 Test?

Your report shows a numeric HE4 level compared with a laboratory’s reference range, which is method‑specific and often adjusted for menopausal status. “Normal” describes the range seen in a general, mostly healthy population. “Optimal” may be defined by your care team in relation to your history, imaging, and other biomarkers. Context matters: a result just above the cutoff can have very different implications in a person with normal imaging versus someone with a new complex mass.

When HE4 falls within the appropriate reference range for your lab and life stage, it generally suggests a lower probability of active epithelial ovarian cancer in the current context. In people undergoing treatment, falling HE4 over time can signal effective tumor debulking or response to therapy. Day to day variation happens, and levels can shift with age, kidney function, smoking, and assay differences.

Higher HE4 levels may indicate increased risk of epithelial ovarian cancer, especially when paired with concerning imaging or elevated CA‑125. Rising values after treatment may point to residual disease or recurrence. That said, elevated HE4 does not equal a diagnosis. Kidney impairment can raise HE4 because the protein is cleared renally, and some benign gynecologic or inflammatory conditions can nudge levels upward. Conversely, certain tumor subtypes (for example, mucinous ovarian tumors) may not produce much HE4, so a low value cannot rule out cancer if imaging is suspicious.

The real strength of this test is pattern recognition over time. Interpreted alongside CA‑125, the ROMA score (which combines HE4, CA‑125, and menopausal status), and imaging, HE4 helps your clinician separate signal from noise. Think of it like tracking your heart‑rate trends during training: one datapoint is interesting, but the trend line is what guides smarter decisions for early detection, treatment monitoring, and long‑term vigilance.

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Frequently Asked Questions About

What do HE4 tests measure?

HE4 tests measure the concentration of human epididymis protein 4 (HE4) in blood (serum); HE4 is a tumor marker used primarily to help detect and monitor epithelial ovarian cancer. Elevated HE4 levels raise the suspicion of malignancy and are often interpreted together with CA‑125 or incorporated into risk algorithms (for example ROMA) to improve diagnostic accuracy. HE4 is not perfectly specific—levels can be affected by age, renal dysfunction and some noncancer conditions—so results are used alongside clinical evaluation and imaging rather than as a definitive diagnosis.

How is your HE4 sample collected?

HE4 is measured from a blood sample collected by a trained phlebotomist via standard venipuncture. Typically a few milliliters of blood are drawn into a serum (or serum‑separator) tube, the sample is allowed to clot, centrifuged, and the separated serum is sent to the laboratory for the HE4 assay.

No special preparation (such as fasting) is usually required, but follow any specific instructions from your healthcare provider or the testing lab; proper labeling and prompt handling help prevent hemolysis or degradation of the sample.

What can my HE4 test results tell me about my cancer risk?

Your HE4 result gives information about the likelihood that a pelvic mass or symptoms could be associated with ovarian cancer, but it is not diagnostic on its own. Higher-than-normal HE4 levels can raise concern and — especially when combined with other markers like CA‑125 and imaging — may indicate a greater probability of malignancy; low or stable HE4 levels lower that probability but do not rule cancer out.

Interpretation depends on clinical context: age, menopausal status, kidney function, smoking and other conditions can raise HE4 independently of cancer, and algorithms (for example ROMA) use HE4 plus other data to estimate risk. Trends over time are often more informative than a single value. Discuss your specific HE4 level and next steps with your clinician, who will interpret it alongside symptoms, exam, imaging and other tests.

How accurate or reliable are HE4 tests?

HE4 is a useful tumor marker for epithelial ovarian cancer that generally shows higher specificity than CA‑125 for distinguishing malignant from benign pelvic conditions, and it complements CA‑125 to improve overall detection when used together (for example in algorithms such as ROMA). It performs well as an adjunctive test but is not sufficiently sensitive or specific on its own to definitively diagnose or rule out cancer.

Reliability is affected by clinical context and test factors: HE4 levels can be influenced by renal function, smoking and age, assay method and chosen cut‑offs, so results must be interpreted alongside imaging, clinical findings and other markers. Serial measurements and combined‑marker risk models give the most clinically useful information; HE4 should not be used in isolation to make management decisions.

How often should I test my HE4 levels?

How often you should test HE4 depends on why it’s being used: for diagnosis or investigation your clinician will order it as needed; for monitoring known ovarian cancer HE4 is commonly checked at regular clinic visits (often every 2–4 months during active treatment and more gradually—e.g., every 3–6 months—during the first few years of follow‑up, with spacing that may increase thereafter), and for long‑term surveillance schedules vary by individual risk and local practice.

HE4 is not recommended as a sole screening test for average‑risk, asymptomatic women; it’s most useful when interpreted alongside CA‑125, imaging, and clinical assessment. Follow the specific testing interval your gynecologist or oncologist prescribes, since the optimal frequency depends on your diagnosis, treatment status, baseline values, and overall risk.

Are HE4 test results diagnostic?

No — HE4 test results highlight patterns of imbalance or resilience and are not, by themselves, medical diagnoses.

HE4 levels must be interpreted alongside symptoms, medical history, physical findings, imaging, and other laboratory or biomarker data by a qualified clinician who can integrate the information and determine appropriate next steps.

How can I improve my HE4 levels after testing?

HE4 is a biomarker used alongside other tests (CA‑125, imaging and clinical exam) to help evaluate ovarian cancer risk; if your HE4 is elevated the most important steps are follow‑up with your clinician for repeat testing, combined marker assessment and appropriate imaging or referral to a gynecologic oncologist rather than trying to “self‑treat” the number.

There’s limited evidence that specific lifestyle changes reliably lower HE4. Focus on addressing underlying causes — if cancer is diagnosed, treatment of the cancer is the way to lower the marker; if kidney dysfunction or medications are contributing, optimizing renal health (control blood pressure and blood sugar, avoid nephrotoxic drugs where possible) and stopping smoking can help. Review all medications and supplements with your doctor and follow their monitoring and treatment plan rather than using unproven remedies to change a biomarker.

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