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Utility of the methylated SEPT9 test for the early detection of colorectal cancer: a systematic review and meta-analysis of diagnostic test accuracy
  1. Rohit Hariharan,
  2. Mark Jenkins
  1. Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia
  1. Correspondence to Dr Mark Jenkins; m.jenkins{at}


Background Circulating tumour DNA from colorectal cancer (CRC) is a biomarker for early detection of the disease and therefore potentially useful for screening. One such biomarker is the methylated SEPT9 (mSEPT9) gene, which occurs during CRC tumourigenesis. This systematic review and meta-analysis aims to establish the sensitivity, specificity and accuracy of mSEPT9 tests for the early diagnosis of CRC.

Methods A systematic search of the relevant literature was conducted using Medline and Embase databases. Data were extracted from the eligible studies and analysed to estimate pooled sensitivity, specificity and diagnostic test accuracy.

Results Based on 19 studies, the pooled estimates (and 95% CIs) for mSEPT9 to detect CRC were: sensitivity 69% (62–75); specificity 92% (89–95); positive likelihood ratio 9.1 (6.1–13.8); negative likelihood ratio 0.34 (0.27–0.42); diagnostic OR 27 (15–48) and area under the curve 0.89 (0.86–0.91). The test has a positive predictive value of 2.6% and negative predictive value of 99.9% in an average risk population (0.3% CRC prevalence), and 9.5% (positive predictive value) and 99.6% (negative predictive value) in a high-risk population (1.2% CRC prevalence).

Conclusion The mSEPT9 test has high specificity and moderate sensitivity for CRC and is therefore a potential alternative screening method for those declining faecal immunochemical test for occult blood (FIT) or other screening modalities. However, it is limited by its poor diagnostic performance for precancerous lesions (advanced adenomas and polyps) and its relatively high costs, and little is known about its acceptability to those declining to use the FIT.

  • colorectal cancer
  • screening
  • cancer epidemiology

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  • Contributors RH conceptualised the study, carried out literature search and selected the studies, provided quality assessment, extraction of data, conducted data analysis, conceptualised the design and draft of the manuscript and approved the final manuscript. MJ contributed to the conception of the paper, supported in selection of papers and provided quality assessment, supported in data analysis and design and draft of the manuscript, proofread and approved the final manuscript.

  • Funding This study was funded by National Health and Medical Research Council (Grant number: APP1117611).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data for this analysis are included in the article or uploaded supplementary material.

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