Abstract and Introduction
Abstract
Aims Guaiac faecal occult blood tests are being replaced by faecal immunochemical tests (FIT). We investigated whether faecal haemoglobin concentration (f-Hb) was related to stage in progression of colorectal neoplasia, studying cancer and adenoma characteristics in an evaluation of quantitative FIT as a first-line screening test.
Methods We invited 66 225 individuals aged 50–74 years to provide one sample of faeces. f-Hb was measured on samples from 38 720 responders. Colonoscopy findings and pathology data were collected on the 943 with f-Hb≥400 ng Hb/ml (80 μg Hb/g faeces).
Results Of the 814 participants with outcome data (median age: 63 years, range 50–75, 56.4% male), 39 had cancer, 190 high-risk adenoma (HRA, defined as ≥3 or any ≥10 mm) and 119 low-risk adenoma (LRA). 74.4% of those with cancer had f-Hb>1000 ng Hb/ml compared with 58.4% with HRA, and 44.1% with no pathology. Median f-Hb concentration was higher in those with cancer than those with no (p<0.002) or non-neoplastic (p<0.002) pathology, and those with LRA (p=0.0001). Polyp cancers had lower concentrations than more advanced stage cancers (p<0.04). Higher f-Hb was also found in those with HRA than with LRA (p<0.006), large (>10 mm) compared with small adenoma (p<0.0001), and also an adenoma displaying high-grade dysplasia compared with low-grade dysplasia (p<0.009).
Conclusions f-Hb is related to severity of colorectal neoplastic disease. This has ramifications for the selection of the appropriate cut-off concentration adopted for bowel screening programmes.
Introduction
Guaiac faecal occult blood tests are used in screening programmes for colorectal (bowel) neoplasia, reducing mortality. Many data have been published and it has been widely documented that gender, age and deprivation affect positivity rates. However, guaiac faecal occult blood tests are not specific for human faecal haemoglobin concentration (f-Hb) and are rapidly being replaced by faecal immunochemical tests (FIT) for haemoglobin, which have many advantages. Quantitative FIT allow the f-Hb concentration used as a cut-off to select those who warrant further investigation, usually colonoscopy, to be selected to give the characteristics deemed desirable by programme organisers.
Sensitivity and specificity can be altered using different cut-off f-Hb, sensitivity increasing as the cut-off is lowered. Moreover, at any cut-off f-Hb, the sensitivity and positive predictive value for significant neoplasia (cancer plus high-risk adenoma) is substantially higher and specificity and negative predictive value lower among men than women. More recently, it has been demonstrated that mean f-Hb in FIT-positive individuals is significantly lower in women compared with men and for younger compared with older participants. Few studies have demonstrated that f-Hb increases as disease becomes more serious, from the normal through low- and high-risk adenomatous polyps (LRA, defined as <3 or any <10 mm, HRA, defined as ≥3 or any ≥10 mm) to invasive cancer. Chen et al showed that, in those with f-Hb below the cut-off, f-Hb at first screening predicted subsequent risk of incident colorectal neoplasia. An accompanying commentary stated that there may be a continuum of increasing risk as f-Hb increases from zero.
To examine this hypothesis further, we carried out an observational study examining colonoscopy and pathology findings in those who were above the f-Hb cut-off selected for use in an evaluation of FIT as a first-line test.