Faecal Occult Blood and Faecal Immunochemical Test

Faecal occult blood tests detect blood in stool that is not visible to the eye.

The guaiac test (gFOBT) detects the peroxidase like activity of haem on a guaiac impregnated card, and is affected by diet and medicines.

The faecal immunochemical test (FIT) uses antibodies specific for human globin, which is mostly digested in the upper gut, so it detects bleeding from the colon and rectum and is not affected by diet.

FIT is read by an analyser and reported as microg haemoglobin/g faeces (microg Hb/g), or ng Hb/mL buffer (1 microg/g is about 5 ng/mL in common devices).

The test is used to screen for colorectal cancer in average risk adults, to triage symptomatic patients with lower gastrointestinal symptoms for urgent colonoscopy, and to investigate iron deficiency anaemia. FIT has largely replaced guaiac testing because it has better sensitivity, a quantitative result and better uptake.

Colorectal cancer is the third commonest cancer and the second leading cause of cancer death worldwide. Screening with FIT reduces colorectal cancer deaths by 15 to 30% in population programmes. About 5 to 10% of those screened by FIT are positive at a threshold of 10 microg Hb/g, and 3 to 8% of positives have cancer, with 30 to 40% having advanced adenomas.

Indications. Population screening of asymptomatic adults (usually 50 to 74 years, or from 45 years in some programmes), triage of symptomatic patients with change in bowel habit, rectal bleeding or abdominal pain, iron deficiency anaemia, and follow up where colonoscopy is not suitable. The test is not used for patients with visible bleeding or suspected acute gastrointestinal haemorrhage, who need direct assessment.

Specimen. A single stool sample (or 2 samples, depending on the programme) collected into a tube with preservative buffer by the patient, using a probe to sample the surface of the stool. Avoid collection during menstruation, active haemorrhoidal bleeding, or with blood in the urine. The sample is stable for 7 to 14 days at room temperature in most devices and longer when refrigerated. Heat and sunlight degrade haemoglobin, and a delay of over 14 days lowers sensitivity.

Positive threshold. Choice depends on the setting and colonoscopy capacity.

• 10 microg Hb/g (about 50 ng Hb/mL): used in many screening programmes, with sensitivity for colorectal cancer of about 80 to 90% and for advanced adenoma of about 30 to 40%, specificity about 90 to 95%.
• 20 microg Hb/g: lower positive rate, and sensitivity for cancer about 75 to 80%.
• 2 to 10 microg Hb/g: used in symptomatic patients, where a threshold under 10 microg Hb/g has negative predictive value over 99% for colorectal cancer and excludes it when the result is under 10 microg Hb/g with no alarm features.
• Qualitative guaiac test: positive on any blue colour change, with sensitivity of 25 to 40% for cancer in a single round, and repeated annual rounds improve it.

Interpretation.

• A positive FIT needs colonoscopy, which finds cancer in about 3 to 8% and advanced adenoma in 30 to 40%.
• A negative FIT in an asymptomatic person reduces risk but does not exclude cancer, and screening is repeated every 1 to 2 years.
• Higher faecal haemoglobin concentration increases the likelihood of cancer and advanced neoplasia, and values over 100 microg Hb/g have a cancer risk of over 10 to 20%.
• A negative FIT in a symptomatic patient with iron deficiency anaemia, weight loss or a palpable mass does not remove the need for further investigation.
• FIT is less sensitive for serrated and flat lesions and for right sided colon neoplasia than for left sided.

Causes of a positive result. Colorectal cancer, advanced and non-advanced adenoma, inflammatory bowel disease, colitis (infective and ischaemic), diverticular disease, haemorrhoids and anal fissure, angiodysplasia, and upper gastrointestinal bleeding in guaiac tests. Aspirin and anticoagulants increase the false positive rate modestly.

Causes of a false positive guaiac result. Red meat, raw vegetables and fruit with peroxidase activity (turnip, radish, horseradish, broccoli, cauliflower), iron preparations, and non-steroidal anti-inflammatory drugs. Vitamin C in doses over 250 mg a day causes false negatives.

Critical values and findings needing immediate action.

• A positive FIT with iron deficiency anaemia, weight loss, rectal bleeding or a change in bowel habit: urgent colonoscopy.
• A positive FIT in a person with a family history of colorectal cancer or Lynch syndrome.
• Any positive test with signs of bowel obstruction, perforation or severe anaemia.

Interferences and pitfalls.

• A positive result is not a diagnosis and needs colonoscopy within a few weeks. A delay of over 3 to 6 months increases the stage of cancer found.
• Repeating a positive FIT hoping for a negative one is wrong. A negative repeat does not reassure.
• Haemoglobin degrades in hot climates and long transit, lowering sensitivity, and sample return should be rapid.
• Different devices have different cut offs in microg Hb/g, so the unit must be confirmed.
• Stool taken from toilet water, or with urine or menstrual blood, gives false positives.
• Upper gastrointestinal bleeding is usually missed by FIT, since globin is digested.
• Interval cancers occur between rounds in about 1 in 5 cases.
• FIT is not used for diagnosis in high risk people (family history, hereditary syndromes), who need colonoscopy.

Special groups.

• Adults 45 to 49 years: rising incidence of early onset colorectal cancer, and some programmes now start screening here.
• Adults over 75 years: screening depends on health and life expectancy.
• Women: slightly lower sensitivity and a higher false positive rate for FIT.
• People on anticoagulants: positive rate is higher, and a positive result still needs colonoscopy.
• Regions: FIT is the practical screening test where colonoscopy is limited, and a positive test needs a clear referral route.

Follow up tests. Colonoscopy with biopsy, full blood count, ferritin, iron studies, CT colonography when colonoscopy is incomplete or not suitable, CEA after a cancer diagnosis, mismatch repair testing of tumour tissue, and upper endoscopy when iron deficiency persists with a negative colonoscopy.