Table 2.
Study characteristics stratified by reference standard.
| Study | Setting | Region | Reference test(s) | Study cancer prevalence (%) | Analyser | Presenting symptoms | n patients | Threshold (µg/g) | Sensitivity % (95% CI) | Specificity % (95% CI) | PPV % (95% CI) | NPV % (95% CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tier 1 - >90% Colonoscopy or CT Colonography | ||||||||||||
| Chapman, 202115 | Primary care | UK (Eng), single centre | Colonoscopy | 5.2 | OC-Sensor | High-risk | 732 | >10 | 89.5 (75.9, 95.8) | 74.1 (70.7, 77.2) | 15.9 (11.6, 21.4) | 99.2 (98, 99.7) |
| >4 (LoD) | 97.4 (86.5, 99.5) | 74.7 (71.1, 78.1) | 19.8 (14.7, 26.1) | 99.8 (98.7, 100) | ||||||||
| HM-JACKarc | >10 | 84.2 (69.6, 92.6) | 78 (74.7, 80.9) | 17.3 (12.5, 23.4) | 98.9 (97.6, 99.5) | |||||||
| >4 | 92.1 (79.2, 97.3) | 70 (66.5, 73.3) | 14.4 (10.5, 19.4) | 99.4 (98.2, 99.8) | ||||||||
| D'Souza, 202016 | Secondary care | UK (Eng), single centre | Colonoscopy | 4.0 | HM-JACKarc | High-risk | 160 | >10 | 87.5 (52.9, 97.8) | 84.2 (77.6, 89.2) | 22.6 (11.4, 39.8) | 99.2 (95.7, 99.9) |
| >2 (LoD) | 100 (67.6, 100) | 71.1 (63.4, 77.7) | 15.4 (8, 27.5) | 100 (96.6, 100) | ||||||||
| Low-risk | 138 | >10 | 100 (51, 100) | 93.3 (87.7, 96.4) | 30.8 (12.7, 57.6) | 100 (97, 100) | ||||||
| >2 (LoD) | 100 (51, 100) | 82.1 (74.7, 87.7) | 14.3 (5.7, 31.5) | 100 (96.6, 100) | ||||||||
| Unstratified | 298 | >10 | 91.7 (64.6, 98.5) | 88.7 (84.5, 91.8) | 25 (14.6, 39.4) | 99.6 (97.8, 99.9) | ||||||
| >2 (LoD) | 100 (75.7, 100) | 76.2 (71, 80.8) | 15 (8.8, 24.4) | 100 (98.3, 100) | ||||||||
| D'Souza (2), 202017 | Secondary care | UK (Eng), multicentre | Colonoscopy | 3.3 | HM-JACKarc | High-risk | 7194 | >10 | 92.2 (88.3, 94.9) | 82.3 (81.4, 83.2) | 16.2 (14.4, 18.2) | 99.7 (99.5, 99.8) |
| >2 (LoD) | 97.7 (95, 98.9) | 63 (61.8, 64.1) | 8.9 (7.9, 10) | 99.9 (99.7, 99.9) | ||||||||
| Low-risk | 1944 | >10 | 86.8 (75.2, 93.5) | 88 (86.5, 89.4) | 16.9 (12.9, 21.8) | 99.6 (99.1, 99.8) | ||||||
| >2 (LoD) | 94.3 (84.6, 98.1) | 71.2 (69.1, 73.2) | 8.4 (6.4, 10.9) | 99.8 (99.3, 99.9) | ||||||||
| Unstratified | 9822 | >10 | 90.9 (87.3, 93.5) | 83.5 (82.8, 84.3) | 16.1 (14.5, 17.8) | 99.6 (99.5, 99.7) | ||||||
| >2 (LoD) | 97 (94.5, 98.3) | 64.9 (63.9, 65.8) | 8.7 (7.9, 9.7) | 99.8 (99.7, 99.9) | ||||||||
| Farrugia, 202018 | Secondary care | UK (Eng), single centre | Colonoscopy, CT Colonography | 6.2 | HM-JACKarc | High-risk | 519 | >10 |
84.8 (69.1, 93.3) | 81.3 (77.6, 84.5) | 23.5 (16.8, 31.9) | 98.8 (97.1, 99.5) |
| Low-risk | 79 | 100 (56.6, 100) | 91.9 (83.4, 96.2) | 45.5 (21.3, 72) | 100 (94.7, 100) | |||||||
| Unstratified | 612 | 86.8 (72.7, 94.2) | 82.2 (78.9, 85.1) | 24.4 (18, 32.3) | 99 (97.6, 99.6) | |||||||
| Godber, 201619 | Secondary care | UK (Sco), single centre | Colonoscopy | 2.3 | HM-JACKarc | Unstratified | 484 | >10 | 100 (74.1, 100) | 76.5 (72.5, 80.1) | 9 (5.1, 15.4) | 100 (98.9, 100) |
| Hererro, 201820 | Secondary care | Spain, multicentre | Colonoscopy | 13.6 | OC-Sensor | Unstratified | 1572 | >10 | 93.5 (89.3, 96.1) | 63.4 (60.8, 65.9) | 28.7 (25.5, 32.2) | 98.4 (97.3, 99) |
| *Khasawneh, 202021 | Primary care | UK (Eng) | CT Colonography | 1.2 | OC-Sensor | CIBH | 5818 | >10 | 88.9 (79.6, 94.3) | 80.8 (79.7, 81.8) | 5.5 (4.3, 6.9) | 99.8 (99.7, 99.9) |
| >4 (LoD) | 91.7 (83, 96.1) | 69.7 (68.5, 70.9) | 3.7 (2.9, 4.6) | 99.9 (99.7, 99.9) | ||||||||
| Laszlo, 202133 | Primary and secondary care | UK (Eng), multicentre | Colonoscopy, CT Colonography, CT, Flexible Sigmoidoscopy | 2.5 | OC-Sensor | High-risk | 3596 | >10 | 83.3 (74.3, 89.6) | 80.1 (78.8, 81.4) | 9.7 (7.8, 12) | 99.5 (99.1, 99.7) |
| >4 (LoD) | 87.8 (79.4, 93) | 73.1 (71.6, 74.5) | 7.7 (6.2, 9.5) | 99.6 (99.2, 99.8) | ||||||||
| >6 | 86.7 (78.1, 92.2) | 76.1 (74.7, 77.5) | 8.5 (6.9, 10.5) | 99.6 (99.2, 99.7) | ||||||||
| McSorley, 202022 | Primary care | UK (Sco), multicentre | Colonoscopy | 5.5 | HM-JACKarc | High-risk | 4841 | >10 | 94.7 (91.4, 96.8) | 47 (45.6, 48.5) | 9.4 (8.4, 10.6) | 99.4 (98.9, 99.6) |
| *Morales-Arraez, 201823 | Unclear | Spain, single centre | Colonoscopy | 11.4 | OC-Sensor | IDA | 245 | >10 | 92.9 (77.4, 98) | 57.1 (50.5, 63.5) | 21.8 (15.4, 30.1) | 98.4 (94.4, 99.6) |
| Mowat, 201624 | Primary care | UK (Sco), single centre | Colonoscopy | 3.7 | OC-Sensor | Unstratified | 750 | >10 | 89.3 (72.8, 96.3) | 79.1 (76, 81.9) | 14.2 (9.8, 20.1) | 99.5 (98.5, 99.8) |
| >4 (LoD) | 100 (87.9, 100) | 43.4 (39.8, 47) | 6.4 (4.5, 9.1) | 100 (98.8, 100) | ||||||||
| Navarro, 202025 | Secondary care | Spain, single centre | Colonoscopy | 5.0 | FOB Gold | Unstratified | 727 | >10 | 94.4 (81.9, 98.5) | 75.1 (71.8, 78.2) | 16.5 (12.1, 22.2) | 99.6 (98.6, 99.9) |
| Rodriguez-Alonso, 201526 | Secondary care | Spain, single centre | Colonoscopy | 3.0 | OC-Sensor | Unstratified | 1003 | >10 | 96.7 (83.3, 99.4) | 79.9 (77.2, 82.3) | 12.9 (9.1, 17.9) | 99.9 (99.3, 100) |
| Schwettmann58 | Secondary care | Norway, single centre | Colonoscopy | 16.0 | FOB Gold | Unstratified | 163 | >10 | 96.2 (81.1, 99.3) | 51.8 (43.5, 60.0) | 27.5 (23.9, 31.5) | 98.6 (91.1, 99.8) |
| Tsapournas, 202027 | Secondary care | Sweden, multicentre | Colonoscopy | 5.3 | QuikRead go | Unstratified | 242 | >10 | 92.3 (66.7, 98.6) | 77.3 (71.4, 82.2) | 18.8 (11.1, 30) | 99.4 (96.9, 99.9) |
| Rectal bleeding | 60 | 100 (61, 100) | 74.1 (61.1, 83.9) | 30 (14.5, 51.9) | 100 (91.2, 100) | |||||||
| Turvill, 202139 | Secondary care | UK (Eng), multicentre | Colonoscopy, CT Colonography, CT, Flexible Sigmoidoscopy | 3.0 | HM-JACKarc | Unstratified | 5040 | >10 | 87.4 (81.2, 91.8) | 80.9 (79.8, 82) | 12.4 (10.5, 14.5) | 99.5 (99.3, 99.7) |
| >2 (LoD) | 92.7 (87.4, 95.9) | 60.7 (59.4, 62.1) | 6.8 (5.8, 8) | 99.6 (99.3, 99.8) | ||||||||
| Tier 2 – other reference standards | ||||||||||||
| Ayling, 201928 | Secondary care | UK (Eng), single centre | Colonoscopy, CT | 3.9 | OC-Sensor | High-risk | 178 | >10 | 66.7 (30, 90.3) | 95.4 (90.4, 97.9) | 40 (16.8, 68.7) | 98.4 (94.4, 99.6) |
| IDA | 137 | 71.4 (35.9, 91.8) | 95.9 (91.8, 98) | 41.7 (19.3, 68) | 98.8 (95.7, 99.7) | |||||||
| Bailey J, 202129 | Primary care | UK (Eng) | Registry F/up | 1.7 |
OC-Sensor | High-risk | 13042 | >10 | 92.1 (87.8, 94.9) | 81.7 (81, 82.4) | 8.2 (7.2, 9.3) | 99.8 (99.7, 99.9) |
| >4 (LoD) | 96.5 (93.2, 98.2) | 69.5 (68.7, 70.3) | 5.3 (4.7, 6) | 99.9 (99.8, 100) | ||||||||
| Bailey S, 202130 | Primary care | UK (Eng) | Registry F/up | 1.1 | HM-JACKarc | Low-risk | 3890 | >10 | 84.3 (72, 91.8) | 85 (83.9, 86.1) | 7 (5.2, 9.2) | 99.8 (99.5, 99.9) |
| Juul, 201831 | Primary care | Denmark | Colonoscopy, Registry F/up | 1.6 | OC-Sensor | Unstratified | 3462 | >10 | 94.4 (84.9, 98.1) | 85.7 (84.4, 86.8) | 9.4 (7.3, 12.2) | 99.9 (99.7, 100) |
| Khan, 202032 | Secondary care | UK (Eng), single centre | Colonoscopy, CT Colonography, CT | 4.8 | HM-JACKarc | High-risk | 928 | >10 | 86.7 (73.8, 93.7) | 83.5 (80.9, 85.8) | 21.1 (15.8, 27.5) | 99.2 (98.2, 99.6) |
| Maclean, 202134 | Secondary care | UK (Eng), single centre | Colonoscopy, CT Colonography, Flexible Sigmoidoscopy | 2.5 | QuikRead go | Low-risk | 553 | >10 | 92.9 (68.5, 98.7) | 70.1 (66.1, 73.8) | 7.5 (4.4, 12.4) | 99.7 (98.5, 100) |
| Mowat, 202135 | Primary care | UK (Sco), single centre | Colonoscopy, CT Colonography, CT, Flexible Sigmoidoscopy, Registry follow-up | 2.0 | HM-JACKarc | Unstratified | 5381 | >10 | 86.7 (78.9, 91.9) | 79.4 (78.3, 80.5) | 7.7 (6.3, 9.4) | 99.7 (99.4, 99.8) |
| >2 (LoD) | 97.1 (91.9, 99) | 49.5 (48.1, 50.8) | 3.7 (3, 4.5) | 99.9 (99.7, 100) | ||||||||
| >7 | 88.6 (81.1, 93.3) | 75.9 (74.7, 77) | 6.8 (5.6, 8.3) | 99.7 (99.5, 99.8) | ||||||||
| Nicholson, 201836 | Primary care | UK (Eng) | Colonoscopy, CTC, Registry F/up | 7.0 | HM-JACKarc | Low-risk | 238 | >10 | 85.7 (48.7, 97.4) | 90.5 (86, 93.6) | 21.4 (10.2, 39.5) | 99.5 (97.4, 99.9) |
| >7 | 85.7 (48.7, 97.4) | 89.2 (84.5, 92.6) | 19.4 (9.2, 36.3) | 99.5 (97.3, 99.9) | ||||||||
| Nicholson, 202037 | Primary care | UK (Eng) | Registry F/up | 1.1 | HM-JACKarc | Unstratified | 9896 | >10 | 90.5 (83.4, 94.7) | 91.3 (90.8, 91.9) | 10.1 (8.3, 12.2) | 99.9 (99.8, 99.9) |
| >7 | 91.4 (84.5, 95.4) | 89.8 (89.2, 90.4) | 8.7 (7.2, 10.6) | 99.9 (99.8, 99.9) | ||||||||
| Pin Vieto, 202038 | Primary care | Spain, multicentre | Registry F/up | 1.4 | OC-Sensor | Unstratified | 5623 | >10 | 80.2 (70.3, 87.5) | 84.1 (83.1, 85) | 6.9 (5.4, 8.7) | 99.7 (99.4, 99.8) |
| CIBH | 1144 | 93.3 (70.2, 98.8) | 82.2 (79.9, 84.3) | 6.5 (3.9, 10.6) | 99.9 (99.4, 100) | |||||||
| Widlak, 201740 | Secondary care | UK (Eng), single centre | Colonoscopy, CT Colonography, CT, Flexible Sigmoidoscopy | 5.8 | HM-JACKarc | Unstratified | 430 | >7 | 88.0 (70, 95.8) | 93.1 (90.2, 95.2) | 44 (31.2, 57.7) | 99.2 (97.7, 99.7) |
| Studies with specific symptom analyses derived from other included cohorts | ||||||||||||
| Cunin, 202041 | Secondary care | UK (Eng), single centre | Colonoscopy, CT Colonography, CT | 5.2 | HM-JACKarc | IDA | 189 | >10 | 80 (58.4, 91.9) | 81.7 (75.1, 86.8) | 34 (22.2, 48.3) | 97.2 (93, 98.9) |
| D'Souza, 202142 | Secondary care | UK (Eng), multicentre | Colonoscopy | 3.3 | HM-JACKarc | IDA | 479 | >10 |
100 (89.6, 100) | 81.6 (77.8, 84.9) | 28.7 (21.2, 37.5) | 100 (99, 100) |
| CIBH | 4249 | 82.7 (73.1, 89.4) | 87.5 (86.5, 88.5) | 11.4 (9.1, 14.2) | 99.6 (99.4, 99.8) | |||||||
| >2 (LoD) | 91.4 (83.2, 95.8) | 68.4 (67, 69.8) | 5.3 (4.3, 6.6) | 99.8 (99.5, 99.9) | ||||||||
| Digby, 202043 | Primary care | UK (Sco), single centre | Colonoscopy | 5.6 | OC-Sensor | Rectal bleeding | 462 | >10 | 96.2 (81.1, 99.3) | 38.3 (33.9, 42.9) | 8.5 (5.8, 12.3) | 99.4 (96.7, 99.9) |
| Hicks, 202144 | Secondary care | UK (Eng), multicentre | Colonoscopy | 3.3 | HM-JACKarc | Rectal bleeding | 3143 | >10 | 96.6 (92.3, 98.5) | 76.6 (75, 78.1) | 16.8 (14.5, 19.5) | 99.8 (99.5, 99.9) |
CI: confidence interval; CIBH: change in bowel habit; IDA: iron-deficiency anaemia; LoD: limit of detection; Unstratified: Symptoms not stratified by “high-risk” or “low-risk” definitions; NG12: NICE guideline 12 (Suspected cancer: recognition and referral) – “high-risk symptoms”; DG30: NICE diagnostics guidance 30 (Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care) – “low-risk symptoms”; * published as an abstract.