Factors associated with false fecal immunochemical test results in colorectal cancer screening

Table 1 Characteristics of participants with complete fecal immunological test data in Tianjin Colorectal Cancer Screening Program, 2012-2020, n (%)

Characteristic	Total (n = 4129947)	Positive FIT (n = 88687)	Negative FIT (n = 4041260)	P value
Age (years), mean ± SD	60.80 ± 8.35	63.14 ± 7.69	60.75 ± 8.36	< 0.001
40-49	460401 (11.1)	5220 (5.9)	455181 (11.3)	< 0.001
50-59	1337212 (32.4)	22160 (25.0)	1315052 (32.5)
60-69	1607369 (38.9)	40561 (45.7)	1566808 (38.8)
70-74	724965 (17.6)	20746 (23.4)	704219 (17.4)
Sex
Male	2197221 (53.2)	46723 (52.7)	2150498 (53.2)	0.002
Female	1932726 (46.8)	41964 (47.3)	1890762 (46.8)
Marital status
Married	3941435 (95.4)	84617 (95.4)	3856818 (95.4)	< 0.001
Unmarried	47806 (1.2)	799 (0.9)	47007 (1.2)
Divorced	29190 (0.7)	598 (0.7)	28592 (0.7)
Widowed	91779 (2.2)	2551 (2.9)	89228 (2.2)
Missing	19737 (0.5)	122 (0.1)	19615 (0.5)
Educational level
Primary school or below	1052467 (25.5)	26043 (29.4)	1026424 (25.4)	< 0.001
Middle school	2621411 (63.5)	55341 (62.4)	2566070 (63.5)
College or above	411895 (10.0)	7011 (7.9)	404884 (10.0)
Missing	44174 (1.1)	292 (0.3)	43882 (1.1)
Occupation
Office clerks and related personnel	158551 (3.8)	2894 (3.3)	155657 (3.9)	< 0.001
Persons in charge of state organizations, large organizations, enterprises and institutions	750333 (18.2)	11083 (12.5)	739250 (18.3)
Soldiers	1555 (0.0)	38 (0.0)	1517 (0.0)
Agriculture workers	1003000 (24.3)	26694 (30.1)	976306 (24.2)
Business and service personnel	286538 (6.9)	3791 (4.3)	282747 (7.0)
Production, transportation, equipment and related personnel	475649 (11.5)	13577 (15.3)	462072 (11.4)
Professional and technical personnel	707738 (17.1)	10571 (11.9)	697167 (17.3)
Others	248457 (6.0)	5777 (6.5)	242680 (6.0)
Unemployed	475567 (11.5)	14130 (15.9)	461437 (11.4)
Missing	22559 (0.5)	132 (0.1)	22427 (0.6)
Smoking status
Never smoker	2003864 (48.5)	41124 (46.4)	1962740 (48.6)	< 0.001
Former smoker	76977 (1.9)	2675 (3.0)	74302 (1.8)
Current smoker	489557 (11.9)	12751 (14.4)	476806 (11.8)
Missing	1559549 (37.8)	32137 (36.2)	1527412 (37.8)
Alcohol consumption
Never drinker	2349521 (56.9)	49412 (55.7)	2300109 (56.9)	< 0.001
Ever drinker	219447 (5.3)	7093 (8.0)	212354 (5.3)
Missing	1560979 (37.8)	32182 (36.3)	1528797 (37.8)
Physical activity
Irregular exercise	1620846 (39.2)	32472 (36.6)	1588374 (39.3)	< 0.001
Regular exercise	948229 (23.0)	24060 (27.1)	924169 (22.9)
Missing	1560872 (37.8)	32155 (36.3)	1528717 (37.8)
BMI (kg/m2)
< 25	1574985 (38.1)	31170 (35.1)	1543815 (38.2)	< 0.001
25-29.9	847303 (20.5)	21280 (24.0)	826023 (20.4)
≥ 30	150992 (3.7)	4276 (4.8)	146716 (3.6)
Missing	1556667 (37.7)	31961 (36.0)	1524706 (37.7)
Chronic diarrhea
No	4012945 (97.2)	77784 (87.7)	3935161 (97.4)	< 0.001
Yes	117002 (2.8)	10903 (12.3)	106099 (2.6)
Chronic constipation
No	3943864 (95.5)	75459 (85.1)	3868405 (95.7)	< 0.001
Yes	186083 (4.5)	13228 (14.9)	172855 (4.3)
Mucus bloody stool
No	4088905 (99.0)	81690 (92.1)	4007215 (99.2)	< 0.001
Yes	41042 (1.0)	6997 (7.9)	34045 (0.8)
Chronic appendicitis/appendectomy
No	4052865 (98.1)	84350 (95.1)	3968515 (98.2)	< 0.001
Yes	77082 (1.9)	4337 (4.9)	72745 (1.8)
Chronic cholecystitis/cholecystectomy
No	4068649 (98.5)	85120 (96.0)	3983529 (98.6)	< 0.001
Yes	61298 (1.5)	3567 (4.0)	57731 (1.4)
Family history of CRC in FDR
No	21415 (0.5)	2168 (2.4)	19247 (0.5)	< 0.001
Yes	4096482 (99.2)	86291 (97.3)	4010191 (99.2)
Unknown	12050 (0.3)	228 (0.3)	11822 (0.3)

FIT: Fecal immunological test; BMI: Body mass index; CRC: Colorectal cancer; FDR: First-degree relative.

Table 2 Characteristics of the study population, n (%)

Characteristics	Total (n = 24890)	Participants with no advanced neoplasm (n = 22586)			Participants with advanced neoplasm (n = 2304)
		False-positive FIT (n = 12471)	True-negative FIT (n = 10115)	P value	False-negative FIT (n = 964)	True-positive FIT (n = 1340)	P value
Age (years), mean ± SD	62.33 ± 7.58	62.54 ± 7.26	61.57 ± 8.02	< 0.001	63.26 ± 7.49	65.32 ± 6.14	< 0.001
40-49	1734 (7.0)	638 (5.1)	1028 (10.2)	< 0.001	55 (5.7)	13 (1.0)	< 0.001
50-59	6506 (26.1)	3404 (27.3)	2653 (26.2)		229 (23.8)	220 (16.4)
60-69	12147 (48.8)	6194 (49.7)	4746 (46.9)		461 (47.8)	746 (55.7)
70-74	4503 (18.1)	2235 (17.9)	1688 (16.7)		219 (22.7)	361 (26.9)
Sex
Male	11911 (47.9)	5865 (47.0)	4612 (45.6)	0.033	596 (61.8)	838 (62.5)	0.761
Female	12979 (52.1)	6606 (53.0)	5503 (54.4)		368 (38.2)	502 (37.5)
Marital status
Married	23907 (96.1)	11984 (96.1)	9706 (96.0)	< 0.001	928 (96.3)	1289 (96.2)	0.172
Unmarried	210 (0.8)	85 (0.7)	106 (1.0)		6 (0.6)	13 (1.0)
Divorced	175 (0.7)	78 (0.6)	83 (0.8)		10 (1.0)	4 (0.3)
Widowed	540 (2.2)	300 (2.4)	191 (1.9)		18 (1.9)	31 (2.3)
Unknown	58 (0.2)	24 (0.2)	29 (0.3)		2 (0.2)	3 (0.2)
Educational level
Primary school or below	5011 (20.1)	3002 (24.1)	1589 (15.7)	< 0.001	149 (15.5)	271 (20.2)	< 0.001
Middle school	16769 (67.4)	8300 (66.6)	6890 (68.1)		659 (68.4)	920 (68.7)
College or above	2945 (11.8)	1109 (8.9)	1546 (15.3)		149 (15.5)	141 (10.5)
Unknown	165 (0.7)	60 (0.5)	90 (0.9)		7 (0.7)	8 (0.6)
Smoking status
Never smoker	19123 (76.8)	9347 (74.9)	8187 (80.9)	< 0.001	708 (73.4)	881 (65.7)	< 0.001
Former smoker	1100 (4.4)	608 (4.9)	360 (3.6)		49 (5.1)	83 (6.2)
Current smoker	4667 (18.8)	2516 (20.2)	1568 (15.5)		207 (21.5)	376 (28.1)
Alcohol consumption
Never drinker	22262 (89.4)	11034 (88.5)	9298 (91.9)	< 0.001	853 (88.5)	1077 (80.4)	< 0.001
Ever drinker	2628 (10.6)	1437 (11.5)	817 (8.1)		111 (11.5)	263 (19.6)
Physical activity
Irregular exercise	13948 (56.0)	7045 (56.5)	5705 (56.4)	0.903	525 (54.5)	673 (50.2)	0.049
Regular exercise	10942 (44.0)	5426 (43.5)	4410 (43.6)		439 (45.5)	667 (49.8)
BMI (kg/m2)
< 25	14126 (56.8)	6790 (54.4)	6086 (60.2)	< 0.001	582 (60.4)	668 (49.9)	< 0.001
25-29.9	9142 (36.7)	4763 (38.2)	3484 (34.4)		336 (34.9)	559 (41.7)
≥ 30	1622 (6.5)	918 (7.4)	545 (5.4)		46 (4.8)	113 (8.4)
Family history of CRC in FDR
No	23095 (92.8)	12069 (96.8)	8862 (87.6)	< 0.001	883 (91.6)	1281 (95.6)	< 0.001
Yes	1795 (7.2)	402 (3.2)	1253 (12.4)		81 (8.4)	59 (4.4)
Hemorrhoids
No	19105 (76.8)	8950 (71.8)	8350 (82.6)	< 0.001	845 (87.7)	960 (71.6)	< 0.001
Yes	5785 (23.2)	3521 (28.2)	1765 (17.4)		119 (12.3)	380 (28.4)
Diverticulum
No	24333 (97.8)	12152 (97.4)	9938 (98.3)	< 0.001	949 (98.4)	1294 (96.6)	0.008
Yes	557 (2.2)	319 (2.6)	177 (1.7)		15 (1.6)	46 (3.4)
Colonoscopy findings
Normal	12057 (48.4)	6566 (52.7)	5491 (54.3)	0.015
Nonadvanced adenoma	10529 (42.3)	5905 (47.3)	4624 (45.7)
Advanced neoplasm	2304 (9.3)				964 (100.0)	1340 (100.0)	-
Advanced adenoma	1780 (7.2)				688 (71.4)	1092 (81.5)	< 0.001
CRC	524 (2.1)				276 (28.6)	248 (18.5)	< 0.001
Stage 0-I	154 (0.6)				64 (6.6)	90 (6.7)	0.001
Stage II-IV	370 (1.5)				212 (22.0)	158 (11.8)	0.001

FIT: Fecal immunological test; BMI: Body mass index; CRC: Colorectal cancer; FDR: First-degree relative.

Table 3 Performance of fecal immunological test for detecting colorectal lesions

Lesions	Sensitivity (95%CI)	Specificity (95%CI)	PPV (95%CI)	NPV (95%CI)	Accuracy (95%CI)
Nonadvanced adenoma	61.3 (59.1-63.6)	45.5 (44.7-46.4)	14.3 (13.5-15.0)	88.9 (88.1-89.6)	47.6 (47.6-47.6)
Advanced adenoma	56.1 (55.1-57.0)	45.5 (44.7-46.4)	47.3 (46.5-48.2)	54.3 (53.3-55.3)	50.5 (50.5-50.5)
Colorectal cancer	47.3 (43.1-51.6)	44.3 (43.7-45.0)	1.8 (1.6-2.0)	97.5 (97.2-97.8)	44.4 (44.4-44.4)
Stage 0-I	58.4 (50.7-66.2)	44.3 (43.7-45.0)	0.7 (0.5-0.8)	99.4 (99.3-99.6)	44.4 (44.4-44.4)
Stage II-IV	42.7 (37.7-47.7)	44.3 (43.7-45.0)	1.2 (1.0-1.3)	98.1 (97.8-98.3)	44.3 (44.3-44.3)
Advanced neoplasm	58.2 (56.1-60.2)	44.8 (44.1-45.4)	9.7 (9.2-10.2)	91.3 (90.8-91.8)	46.0 (46.0-46.0)
Any neoplasm	56.5 (55.6-57.3)	45.5 (44.7-46.4)	52.5 (51.6-53.3)	49.6 (48.6-50.5)	51.2 (51.2-51.2)

PPV: Positive predictive value; NPV: Negative predictive value; 95%CI: 95% confidence interval.

Table 4 Factors associated with false-positive and false-negative fecal immunological test for the detection of advanced colorectal neoplasm

Variables	False-positive FIT (true negative as reference)			False-negative FIT (true positive as reference)
	Crude OR (95%CI)	Adjusted OR (95%CI)	P value	Crude OR (95%CI)	Adjusted OR 95%CI)	P value
Age (per additional year)	1.02 (1.01-1.02)	1.01 (1.01-1.02)	< 0.001	0.96 (0.94-0.97)	0.96 (0.94-0.97)	< 0.001
Sex
Female	1	1		1	1
Male	1.06 (1.01-1.12)	0.91 (0.85-0.96)	0.001	0.97 (0.82-1.15)	1.23 (1.00-1.49)	0.045
Smoking status
Never smoker	1	1		1	1
Former smoker	1.48 (1.29-1.69)	1.39 (1.21-1.60)	< 0.001	0.73 (0.51-1.06)	1.03 (0.68-1.55)	0.881
Current smoker	1.41 (1.31-1.51)	1.36 (1.26-1.48)	< 0.001	0.69 (0.56-0.83)	0.73 (0.57-0.95)	0.017
Never drinker	1	1		1	1
Ever drinker	1.48 (1.35-1.62)	1.3 (1.17-1.44)	< 0.001	0.53 (0.42-0.68)	0.60 (0.45-0.81)	< 0.001
Physical activity
Irregular exercise	1	1		1	1
Regular exercise	1.00 (0.95-1.05)	0.90 (0.85-0.95)	< 0.001	0.84 (0.71-10)	1.07 (0.88-1.31)	0.474
BMI (kg/m2)
< 25	1	1		1	1
25-29.9	1.23 (1.16-1.30)	1.18 (1.11-1.25)	< 0.001	0.69 (0.58-0.82)	0.75 (0.61-0.91)	0.004
≥ 30	1.51 (1.35-1.69)	1.42 (1.27-1.59)	< 0.001	0.47 (0.33-0.67)	0.56 (0.38-0.83)	0.004
Hemorrhoid
No	1	1		1	1
Yes	1.86 (1.74-1.99)	1.85 (1.73-1.97)	< 0.001	0.36 (0.28-0.45)	0.58 (0.46-0.74)	< 0.001
Diverticulum
No	1	1		1	1
Yes	1.47 (1.22-1.77)	1.26 (1.04-1.52)	0.018	0.44 (0.25-0.80)	0.75 (0.41-1.39)	0.359
Presence of nonadvanced adenoma
No	1	1
Yes	1.07 (1.01-1.13)	0.99 (0.94-1.05)	0.753
Presence of any advanced adenoma ≥ 10 mm
No				1	1
Yes				0.21 (0.18-0.25)	0.08 (0.06-0.12)	< 0.001
Presence of any advanced adenoma of high-grade dysplasia
No				1	1
Yes				0.68 (0.49-0.94)	0.66 (0.45-0.98)	0.041
Presence of any advanced adenoma with villous/tubulovillous features
No				1	1
Yes				0.62 (0.40-0.97)	0.76 (0.44-1.31)	0.248
Presence of CRC
No				1	1
Stage 0-I CRC				1.13 (0.81-1.58)	0.13 (0.08-0.22)	< 0.001
Stage II-IV CRC				2.13 (1.70-2.67)	0.26 (0.17-0.39)	< 0.001

FIT: Fecal immunological test; OR: Odds ratio; 95%CI: 95% confidence interval; BMI: Body mass index; CRC: Colorectal cancer.