Socioeconomic position and the pre-diagnostic interval among patients diagnosed with head and neck squamous cell carcinoma - a population-based study from DAHANCA

Figures & data

Table 1. Descriptive characteristics of patients in the analyzed cohort.

	All sites	Glottic larynx	Non-glottic larynx	HPV+ oropharynx	HPV- oropharynx	Hypopharynx	Oral cavity
	(n = 11 024)	(n = 1 722)	(n = 968)	(n = 2 626)	(n = 1 557)	(n = 1 035)	(n = 3 116)
Characteristics	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)
Age
Median [IQR]	64 [57;71]	68 [61;74]	66 [58;72]	60 [54;67]	63 [57;69]	64 [58;70]	65 [58;73]
Gender
Female	2 958 (27)	227 (13)	266 (27)	612 (23)	468 (30)	184 (18)	1 201 (39)
Male	8 066 (73)	1 495 (87)	702 (73)	2 014 (77)	1 089 (70)	851 (82)	1 915 (61)
Year of diagnosis
2008–2010	2 353 (21)	443 (26)	276 (29)	415 (16)	303 (19)	208 (20)	708 (23)
2011–2013	2 801 (25)	450 (26)	276 (29)	639 (24)	416 (27)	276 (27)	744 (24)
2014–2016	2 941 (27)	427 (25)	227 (23)	746 (28)	439 (28)	268 (26)	834 (27)
2017–2019	2 929 (27)	402 (23)	189 (20)	826 (31)	399 (26)	283 (27)	830 (27)
Education
Short	2 934 (27)	537 (31)	355 (37)	487 (19)	398 (26)	280 (27)	877 (28)
Medium	6 141 (56)	927 (54)	490 (51)	1 474 (56)	938 (60)	610 (59)	1 702 (55)
Long	1 949 (18)	258 (15)	123 (13)	665 (25)	221 (14)	145 (14)	537 (17)
Income
Low	3 009 (27)	448 (26)	315 (33)	492 (19)	545 (35)	329 (32)	880 (28)
Medium	4 873 (44)	790 (46)	443 (46)	1 070 (41)	711 (46)	496 (48)	1 363 (44)
High	3 142 (29)	484 (28)	210 (22)	1 064 (41)	301 (19)	210 (20)	873 (28)
Cohabitation status
Living alone	4 958 (45)	685 (40)	496 (51)	842 (32)	854 (55)	553 (53)	1 528 (49)
Cohabiting	6 066 (55)	1 037 (60)	472 (49)	1 784 (68)	703 (45)	482 (47)	1 588 (51)
Pre-diagnostic interval
Median [IQR], weeks	10 [5;21]	15 [8;29]	12 [7;21]	8 [4;16]	9 [5;17]	11 [6;21]	10 [5;21]
Missing information	1 910 (17)	300 (17)	165 (17)	313 (12)	207 (13)	139 (13)	786 (25)
Primary symptoms^a
Missing information	1024 (9)	143 (8)	99 (10)	143 (5)	103 (7)	64 (6)	472 (15)
Reported symptoms*	10 000 (91)	1 579 (92)	869 (90)	2 483 (95)	1 454 (93)	971 (94)	2 644 (85)
Pain (% of*)	4 125 (41)	98 (6)	403 (46)	858 (35)	868 (60)	480 (49)	1 418 (54)
Neck lymph node (% of*)	2 166 (22)	11 (1)	90 (10)	1 378 (55)	324 (22)	252 (26)	111 (4)
Hoarseness (% of*)	2 153 (22)	1 493 (95)	405 (47)	34 (1)	34 (2)	176 (18)	11 ()
Dysphagia (% of*)	1 417 (14)	30 (2)	192 (22)	259 (10)	369 (25)	382 (39)	185 (7)
Lump in throat (% of*)	1 273 (13)	7 ()	59 (7)	341 (14)	169 (12)	79 (8)	618 (23)
Otalgia (% of*)	192 (11)	35 (2)	129 (15)	327 (13)	275 (19)	180 (19)	146 (6)
Ulceration (% of*)	931 (9)	NA	NA	26 (1)	73 (5)	NA	825 (31)
Weight loss (% of*)	793 (8)	27 (2)	104 (12)	111 (4)	186 (13)	154 (16)	211 (8)
Comorbidity score
HN-CCI = 0	7 833 (71)	1 231 (71)	606 (63)	2 172 (83)	979 (63)	664 (64)	2 181 (70)
HN-CCI ≥ 1	3 191 (29)	491 (29)	362 (37)	454 (17)	578 (37)	371 (36)	935 (30)
Stage (TNM-7)^b
Early	3 965 (36)	1 402 (81)	326 (34)	259 (10)	333 (21)	107 (10)	1 538 (49)
Advanced	7 059 (64)	320 (19)	642 (66)	2 367 (90)	1 224 (79)	928 (90)	1 578 (51)

HPV = human papillomavirus, IQR = Interquartile range, HN-CCI = Revised Charlson Comorbidity Index for Head and Neck Cancer, NA: Not applicable because of micro data (n < 5 observations).

^a Frequently reported symptoms according to the predefined list provided in eTable 1 (not all symptoms are applied because of micro-data in strata).

^b Missing information on stage (n = 126) are imputed according to the proportion in each stratum for complete cases to avoid micro-data (n < 5 observations).

Table 2. Adjusted estimates with 95% confidence intervals for the interval from reported symptom onset to diagnosis.

	All included sites	Glottic larynx	Non-glottic larynx	HPV+ oropharynx	HPV- oropharynx	Hypopharynx	Oral cavity
	(n = 9 114)	(n = 1 422)	(n = 803)	(n = 2 313)	(n = 1 350)	(n = 896)	(n = 2 330)
Parameter	Estimate^a [95% CI]	Estimate^a [95% CI]	Estimate^a [95% CI]	Estimate^a [95% CI]	Estimate^a [95% CI]	Estimate^a [95% CI]	Estimate^a [95% CI]
Age
Q1: 40-56	0.95 [0.89;1.02]	1.03 [0.86;1.23]	1.24 [1.00;1.53]	0.89 [0.76;1.04]	1.00 [0.83;1.20]	1.18 [0.93;1.48]	1.24 [1.08;1.43]
Q2: 57-63	0.99 [0.92;1.05]	1.08 [0.92;1.28]	1.05 [0.86;1.29]	0.98 [0.84;1.15]	1.05 [0.88;1.25]	1.33 [1.08;1.65]	1.09 [0.95;1.25]
Q3: 64-70	0.99 [0.92;1.05]	1.06 [0.92;1.23]	1.06 [0.88;1.28]	0.95 [0.81;1.12]	0.92 [0.77;1.09]	1.23 [1.00;1.52]	1.04 [0.91;1.19]
Q4: 71-96	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Gender
Female	1.07 [1.01;1.12]	0.93 [0.78;1.10]	1.11 [0.95;1.30]	1.21 [1.08;1.35]	1.05 [0.92;1.20]	1.17 [0.95;1.42]	1.16 [1.05;1.28]
Male	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Period of diagnosis
2008– 2010	1.22 [1.14;1.31]	1.15 [0.97;1.37]	1.09 [0.89;1.35]	1.38 [1.19;1.60]	1.07 [0.90;1.28]	1.03 [0.82;1.29]	1.02 [0.89;1.17]
2011– 2013	1.07 [1.01;1.15]	1.02 [0.86;1.21]	1.00 [0.82;1.23]	1.29 [1.14;1.47]	1.08 [0.92;1.28]	0.88 [0.72;1.08]	0.82 [0.71;0.93]
2014– 2016	1.01 [0.95;1.08]	0.98 [0.83;1.16]	1.10 [0.89;1.36]	1.06 [0.93;1.19]	1.09 [0.93;1.28]	0.86 [0.70;1.05]	0.85 [0.74;0.96]
2017– 2019	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Education
Short	0.97 [0.90;1.05]	0.80 [0.67;0.96]	0.84 [0.67;1.05]	1.00 [0.86;1.16]	0.82 [0.67;1.00]	0.99 [0.77;1.28]	0.94 [0.81;1.09]
Medium	0.97 [0.91;1.03]	0.78 [0.66;0.92]	0.81 [0.65;1.00]	0.98 [0.87;1.10]	0.98 [0.82;1.18]	0.98 [0.78;1.23]	0.94 [0.82;1.08]
Long	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Income
Low	1.07 [1.01;1.15]	0.94 [0.80;1.10]	0.88 [0.72;1.08]	1.16 [1.01;1.33]	0.94 [0.79;1.12]	0.99 [0.80;1.23]	1.00 [0.88;1.14]
Medium	0.99 [0.94;1.05]	0.94 [0.81;1.08]	0.95 [0.79;1.15]	1.03 [0.93;1.15]	0.89 [0.75;1.05]	0.87 [0.71;1.06]	0.97 [0.86;1.09]
High	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Cohabiting status
Living alone	1.02 [0.98;1.07]	0.96 [0.85;1.08]	0.96 [0.84;1.11]	0.96 [0.87;1.07]	1.02 [0.91;1.15]	1.07 [0.93;1.25]	1.06 [0.96;1.16]
Cohabiting	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Comorbidity
HN-CCI > = 1	0.95 [0.90;1.00]	1.16 [1.01;1.32]	0.78 [0.68;0.91]	0.92 [0.81;1.05]	0.95 [0.84;1.07]	0.87 [0.74;1.02]	0.90 [0.81;1.00]
HN-CCI = 0	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Primary symptoms^b
Pain	1.11 [1.06;1.16]	1.04 [0.81;1.32]	1.02 [0.88;1.18]	1.36 [1.23;1.50]	1.37 [1.22;1.55]	1.17 [1.01;1.36]	1.20 [1.09;1.32]
No Pain	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Neck lymph node	0.65 [0.61;0.69]	0.39 [0.20;0.79]	0.66 [0.53;0.84]	0.73 [0.67;0.81]	0.71 [0.61;0.81]	0.66 [0.56;0.78]	0.77 [0.61;0.98]
No neck lymph node	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Hoarseness	1.61 [1.52;1.70]	1.71 [1.32;2.22]	1.17 [1.02;1.35]	1.38 [0.90;2.11]	0.78 [0.52;1.17]	1.38 [1.14;1.68]	1.51 [0.72;3.15]
No hoarseness	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Dysphagia	1.22 [1.14;1.31]	1.10 [0.72;1.70]	1.03 [0.87;1.22]	1.34 [1.14;1.57]	1.41 [1.23;1.61]	1.44 [1.24;1.67]	1.20 [0.99;1.44]
No dysphagia	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Lump in throat	0.94 [0.87;1.01]	0.88 [0.36;2.19]	1.09 [0.81;1.45]	1.18 [1.03;1.36]	0.98 [0.81;1.18]	1.02 [0.77;1.34]	0.97 [0.87;1.09]
No lump in throat	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Otalgia	1.17 [1.08;1.01]	1.45 [0.99;2.11]	1.13 [0.93;1.38]	1.46 [1.27;1.68]	1.22 [1.05;1.41]	1.08 [0.89;1.31]	1.15 [0.94;1.41]
No otalgia	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]
Ulceration	0.97 [0.90;1.06]	NA	NA	1.40 [0.87;2.25]	0.80 [0.60;1.05]	NA	1.02. [0.92;1.13]
No ulceration	1.00 [ref.]	NA	NA	1.00 [ref.]	1.00 [ref.]	NA	1.00 [ref.]
Weight loss	1.25 [1.14;1.36]	0.74 [0.47;1.16]	1.23 [0.99;1.52]	1.48 [1.17;1.87]	1.28 [1.07;1.53]	1.35 [1.11;1.65]	1.27 [1.06;1.52]
No weight loss	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]	1.00 [ref.]

HPV = human papillomavirus, HN-CCI = Revised Charlson Comorbidity Index for Head and Neck Cancer, NA: Not applicable because of micro data (n < 5 observations).

^a Estimate (e^β-1) with 95% confidence intervals in brackets adjusted for age (cont.), gender, calendar year (cont.).

^b Frequently reported symptoms according to the predefined list provided in eTable 1 (not all symptoms are applied because of few events in strata).

Figure 1. Average weekly number of contacts prior to diagnosis and change-point for which the average weekly number of contacts changed, with 95% confidence intervals, for patients with short (A) and long (B) education.

Figure 2. Median interval and IQR between patient-reported symptom onset and diagnosis and change-point for which the average weekly number of consultations changed, by subsite and educational level. IQR: Interquartile range. CI: confidence intervals.

Table 3. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for advanced disease stage (TNM-7: III-IV vs. I-II), by subsite.

	All included sites	Glottic larynx	Non-glottic larynx	HPV+ oropharynx	HPV- oropharynx	Hypopharynx	Oral cavity
	OR^a [95% CI]	OR^a [95% CI]	OR^a [95% CI]	OR^a [95% CI]	OR^a [95% CI]	OR^a [95% CI]	OR^a [95% CI]
Educational level
Short	0.99 [0.88;1.12]	1.51 [1.01;2.25]	0.82 [0.53;1.28]	1.01 [0.68;1.50]	1.22 [0.82;1.82]	0.97 [0.45;2.07]	1.72 [1.38;2.15]
Medium	0.95 [0.85;1.06]	1.18 [0.81;1.73]	0.91 [0.59;1.39]	0.98 [0.72;1.33]	1.12 [0.79;1.58]	0.55 [0.28;1.08]	1.21 [0.99;1.48]
Long	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]
Income
Low	0.99 [0.89;1.11]	1.67 [1.18;2.38]	1.38 [0.94;2.03]	0.64 [0.46;0.90]	0.98 [0.69;1.40]	0.77 [0.41;1.46]	1.57 [1.28;1.91]
Medium	0.99 [0.90;1.09]	1.66 [1.21;2.27]	1.08 [0.76;1.52]	0.96 [0.71;1.29]	0.95 [0.68;1.32]	0.68 [0.38;1.20]	1.20 [1.00;1.42]
High	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]
Cohabitation status
Living alone	1.32 [1.22;1.43]	1.88 [1.47;2.41]	1.33 [1.01;1.75]	1.39 [1.04;1.86]	1.17 [0.92;1.50]	1.17 [0.78;1.75]	1.60 [1.38;1.84]
Cohabiting	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]
Interval from reported symptom onset to diagnosis
Q1:	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]	1.00 [Ref]
Q2:	1.05 [0.93;1.19]	0.82 [0.55;1.22]	0.89 [0.58;1.37]	1.41 [0.91;2.17]	0.98 [0.67;1.42]	0.91 [0.49;1.66]	1.30 [1.03;1.64]
Q3:	1.10 [0.98;1.25]	1.22 [0.84;1.79]	0.90 [0.59;1.38]	0.99 [0.67;1.47]	0.99 [0.68;1.46]	1.36 [0.70;2.65]	1.40 [1.11;1.76]
Q4:	0.97 [0.86;1.10]	1.52 [1.05;2.20]	0.65 [0.43;0.98]	0.89 [0.61;1.32]	0.85 [0.58;1.22]	0.78 [0.43;1.41]	1.12 [0.89;1.41]

^a Adjusted for age (cont.), gender, calendar year (cont.), patients with missing information on stage (n = 126) are excluded from the numbers provided in Table 1.

HPV = human papillomavirus, HN-CCI = Revised Charlson Comorbidity Index for Head and Neck Cancer.

Data availability statement

The data used in this study were de-identified, linked and accessed through the Danish Cancer Institute’s secure server at Statistics Denmark. The authors do not have permission to share the data. In agreement with the General Data Protection Regulation the study is registered in the Danish Cancer Society’s internal project register database (journal number 2018-DCRC-0034).