Participant-Related Risk Factors for False-Positive and False-Negative Fecal Immunochemical Tests in Colorectal Cancer Screening: Systematic Review and Meta-Analysis

OBJECTIVES: Colorectal cancer (CRC) screening using fecal immunochemical tests (FIT) may reduce CRC-related mortality but its effectiveness is influenced by the limited accuracy of FIT. Identifying individuals at increased risk of a false FIT result could improve screening, but the available evidence is conflicting. We performed a systematic review and meta-analysis on risk factors for false-positive and false-negative FIT results in CRC screening. METHODS: A systematic search in MEDLINE, EMBASE, and Cochrane Library identified publications (before 29 January 2017) on risk factors (known at time of FIT invitation) associated with false FIT results (presence/absence of advanced neoplasia) in a CRC screening setting. Risk of bias was assessed using QUIPS. In meta-analysis, summary relative risk ratios and corresponding 95% confidence intervals were calculated for each risk factor. RESULTS: Of 518 records identified, 14 studies with 54,499 participants in total were included for analysis. In meta-analysis, male sex was associated with a significantly lower risk of false-positivity (RR 0.84, CI 0.74-0.94), whereas participants using non-steroidal anti-inflammatory drugs (NSAIDs) had a higher risk (RR 1.16, CI 1.06-1.27). The use of anticoagulants was most frequently studied, without a significant effect on FIT positivity. Males (RR 1.83, CI 1.53-2.19), participants with a family history for CRC (RR 1.61, CI 1.19-2.15), hyperglycemia (RR 1.29, CI 1.02-1.65), hypertension (RR 1.50, CI 1.14-1.98), obesity (RR 1.38, CI 1.11-1.71), and (former) smokers (RR 1.93, CI 1.52-2.45) were all at significantly higher risk for false-negative results. Age was not found to have a systematic effect on either FIT false-positivity or false-negativity in meta-analysis. CONCLUSIONS: Multiple risk factors, known at time of FIT invitation, are associated with false FIT results in CRC screening. This information can be used to identify populations risking false reassurance after a negative result or unnecessary colonoscopy after a positive result, and to further optimize CRC screening effectiveness.