Article Figures & Data
Tables
- Table 1.
Selected characteristics of incident cases of esophageal cancer and their matched controls in each cohort study
ACS CPS-II NC Cohort PLCO Cohort Characteristics Cases Controls Cases Controls Matching variables N = 51 N = 153 P N = 74 N = 219 P Age at mouthwash collection; mean (SD) 71.4 (6.1) 71.4 (6.0) 0.97 65.2 (5.6) 65.3 (5.5) 0.82 Months from mouthwash collection to diagnosis (cases) or riskset (controls); mean (SD) 35.3 (24.5) 35.3 (24.3) 1.00 52.6 (30.1) 53.3 (29.9) 0.85 Gender; n % 1.00 0.97 Female 8 (15.7) 24 (15.7) 15 (20.3) 44 (20.1) Male 43 (84.3) 129 (84.3) 59 (79.7) 175 (79.9) Race/ethnicity; n % 1.00 0.99 Caucasian 50 (98.0) 150 (98.0) 67 (90.5) 198 (90.4) African American/other 1 (2.0) 3 (2.0) 7 (9.5) 21 (9.6) Unmatched variables BMI group (kg/m2); n (%) 0.38 0.89 <25 22 (43.1) 50 (32.7) 18 (24.3) 55 (25.1) 25–29.9 18 (35.3) 63 (41.2) 37 (50.0) 113 (51.6) ≥30 5 (9.8) 26 (17.0) 17 (23.0) 48 (21.9) Missing 6 (11.8) 14 (9.1) 2 (2.7) 3 (1.4) Smoking status; n (%) 0.01 0.01 Never 11 (21.6) 60 (39.2) 20 (27.0) 99 (45.2) Former 32 (62.7) 86 (56.2) 44 (59.5) 108 (49.3) Current 8 (15.7) 7 (4.6) 10 (13.5) 12 (5.5) Pack-years, former and current smokers; mean (SD) 31.5 (26.7) 31.9 (31.9) 0.94 54.0 (30.4) 36.2 (28.3) 0.0002 Alcohol consumption; n (%) None 16 (31.4) 55 (35.9) 0.55 23 (31.1) 73 (33.3) 0.72 Drinker 35 (68.6) 98 (64.1) 51 (68.9) 146 (66.7) Drinks/week; median (IQR) 5.7 (2.1–18.1) 3.4 (1.0–9.1) 0.10 5.8 (1.1–14.6) 2.4 (1.1–7.0) 0.13 Education; n % 0.94 0.41 <12 grade 3 (5.9) 12 (7.8) 2 (2.7) 17 (7.8) High school/vocational 15 (29.4) 39 (25.5) 30 (40.5) 77 (35.2) Some college 10 (19.6) 33 (21.5) 10 (13.5) 38 (17.4) College graduate 10 (19.6) 29 (19.0) 13 (17.6) 39 (17.8) Graduate degree 12 (23.5) 39 (25.5) 18 (24.3) 48 (21.9) Missing 1 (2.0) 1 (0.7) 1 (1.4) — Marital status; n % 0.48 0.85 Married 40 (78.4) 113 (73.9) 60 (81.1) 175 (79.9) Separated/divorced — 2 (1.3) 7 (9.5) 20 (9.1) Widowed 2 (3.9) 12 (7.8) 4 (5.4) 18 (8.2) Never married — — 2 (2.7) 6 (2.7) Missing 9 (17.6) 26 (17.0) 1 (1.4) — Tumor histology; n (%) Adenocarcinoma 31 (60.8) N/A 49 (66.2) N/A Squamous cell carcinoma 12 (23.5) N/A 16 (21.6) N/A Other 8 (15.7) N/A 9 (12.2) N/A Abbreviations: IQR: interquartile range; SD: standard deviation.
- Table 2.
Associations of HPV16, high-risk (HR) oncogenic HPV, and other α HPV types with risks of esophageal cancer and histologic type
Cases (n = 125) Controls (n = 371)a Adjusted modelb All esophageal cancersα HPV type N (%) N (%) ORa (95% CI) P Permutated Pd HPV16 1 (0.8) 6 (1.6) 0.54 (0.10–4.84) 0.58 >0.999 HR-HPVsc excluding HPV16 8 (6.4) 18 (4.9) 1.21 (0.49–2.99) 0.68 >0.999 NonHR HPV types 16 (12.8) 36 (9.7) 1.47 (0.77–2.81) 0.24 0.801 Any α HPV 23 (18.4) 53 (14.3) 1.39 (0.78–2.48) 0.26 0.823 ESCC α HPV type Cases (n = 28) Controls (n = 83) ORa (95% CI) P Permutated Pd HPV16 0 (0) 1 (1.2) — — >0.999 HR-HPVsc excluding HPV16 3 (10.7) 1 (1.2) 10.52 (1.01–108.5) 0.048 0.236 Non-HR HPV types 4 (14.3) 11 (13.3) 1.68 (0.41–6.91) 0.48 >0.999 Any α HPV 6 (21.4) 13 (15.7) 2.21 (0.61–8.05) 0.23 0.772 Esophageal cancer: adenocarcinoma α HPV type Cases (n = 80) Controls (n = 238) ORa (95% CI) P Permutated Pd HPV16 1 (1.3) 5 (2.1) 0.60 (0.10–5.85) 0.66 >0.999 HR-HPVsc excluding HPV16 3 (3.8) 14 (5.9) 0.52 (0.14–1.96) 0.33 >0.999 NonHR HPV types 8 (10.0) 21 (8.8) 1.21 (0.51–2.86) 0.66 >0.999 Any α HPV 12 (15.0) 35 (14.6) 0.98 (0.46–2.08) 0.96 >0.999 ↵aOne control had missing α HPV exposure and thus was excluded from these analyses.
↵bOR and 95% CI were estimated from CLR models adjusted for smoking, alcohol consumption, and study cohort.
↵cHigh-risk (HR) oncogenic HPVs include HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59.
↵dPermutated P values were calculated to account for multiple comparisons (see Material and Methods).
- Table 3.
Associations of β and γ HPV species and types with risk of esophageal cancer
Cases (n = 125) Controls (n = 372) Adjusted modela β HPV Speciesb N (%) N (%) ORa (95% CI) P Permutated Pc Any β HPV 81 (64.8) 205 (55.1) 1.57 (1.00–2.47) 0.048 0.538 Any β 1 HPV 59 (47.2) 146 (39.3) 1.49 (0.96–2.31) 0.08 0.716 Any β 2 HPV 64 (51.2) 160 (43.0) 1.34 (0.88–2.05) 0.17 0.951 Any β 3 HPV 24 (19.2) 60 (16.1) 1.26 (0.73–2.18) 0.41 >0.999 Specific β HPV typesb β 1 HPV5 22 (17.6) 42 (11.3) 1.75 (0.97–3.16) 0.07 0.655 β 1 HPV12 11 (8.8) 27 (7.3) 1.24 (0.58–2.65) 0.58 >0.999 β 1 HPV20 22 (17.6) 46 (12.4) 1.53 (0.87–2.70) 0.14 0.908 β 1 HPV36 15 (12.0) 33 (8.9) 1.20 (0.61–2.35) 0.60 >0.999 Clade of β 1 HPVs 5, 36, 47, & 143 26 (20.8) 59 (15.9) 1.34 (0.79–2.27) 0.28 0.995 β 1 HPV105 14 (11.2) 29 (7.8) 1.31 (0.65–2.63) 0.45 >0.999 β 1 HPV124 10 (8.0) 28 (7.5) 1.01 (0.46–2.21) 0.99 >0.999 β 2 HPV23 12 (9.6) 26 (7.0) 1.34 (0.64–2.81) 0.44 >0.999 β 2 HPV37 8 (6.4) 28 (7.5) 0.97 (0.42–2.27) 0.95 >0.999 β 2 HPV38 24 (19.2) 57 (15.3) 1.28 (0.75–2.18) 0.37 >0.999 β 2 HPV107 17 (13.6) 29 (7.8) 1.85 (0.94–3.62) 0.08 0.703 γHPV Speciesb Any γ HPV 53 (42.4) 125 (33.6) 1.38 (0.89–2.13) 0.15 0.924 Any γ 7 HPV 20 (16.0) 49 (13.2) 1.11 (0.62–2.01) 0.72 >0.999 Any γ 8 HPV 13 (10.4) 38 (10.2) 1.02 (0.52–2.01) 0.95 >0.999 Any γ 10 HPV 13 (10.4) 28 (7.5) 1.33 (0.66–2.71) 0.42 >0.999 Any γ 12 HPV 8 (6.4) 19 (5.1) 1.34 (0.56–3.20) 0.51 >0.999 Any γ 15 HPV 13 (10.4) 28 (7.5) 1.39 (0.66–2.89) 0.39 >0.999 - Table 4.
Associations of β and γ HPVs species and types with risk of histologic type of esophageal cancer
A. ESCC Cases (n = 28) Controls (n = 83) Adjusted modela N (%) N (%) ORa (95% CI) P Permutated Pc β HPV speciesb Any β HPV 14 (50.0) 41 (49.4) 1.05 (0.37–2.97) 0.93 >0.999 Any β 1 HPV 10 (35.7) 27 (32.5) 1.19 (0.42–3.35) 0.75 >0.999 Any β 2 HPV 11 (39.3) 33 (39.8) 0.99 (0.36–2.72) 0.99 >0.999 Any β 3 HPV 3 (10.7) 19 (22.9) 0.35 (0.1–1.48) 0.15 0.792 Specific β HPV typesb β 1 HPV5 5 (17.9) 10 (12.1) 1.56 (0.44–5.53) 0.49 >0.999 β 1 HPV12 3 (10.7) 9 (10.8) 1.24 (0.26–5.79) 0.79 >0.999 β 1 HPV20 3 (10.7) 8 (9.6) 1.10 (0.25–4.81) 0.89 >0.999 β 1 HPV36 4 (14.3) 6 (7.2) 1.72 (0.36–8.14) 0.50 >0.999 Clade of β 1 HPVs 5, 36, 47, & 143 6 (21.4) 12 (14.5) 1.31 (0.39–4.39) 0.66 >0.999 β 2 HPV23 2 (7.1) 6 (7.2) 1.31 (0.20–8.38) 0.78 >0.999 β 2 HPV38 4 (14.3) 16 (19.3) 0.62 (0.18–2.11) 0.45 >0.999 γ HPV speciesb Any γ HPV 12 (42.9) 26 (31.3) 1.31 (0.51–3.31) 0.57 >0.999 Any γ 7 HPV 3 (10.7) 6 (7.2) 0.81 (0.15–4.48) 0.81 >0.999 Any γ 8 HPV 3 (10.7) 9 (10.8) 0.61 (0.12–3.11) 0.55 >0.999 Any γ 10 HPV 4 (14.3) 8 (9.6) 1.46 (0.37–5.82) 0.59 >0.999 Any γ 15 HPV 3 (10.7) 8 (9.6) 1.22 (0.29–5.14) 0.79 >0.999 B. Esophageal adenocarcinoma Cases (n = 80) Controls (n = 239) Adjusted modela N (%) N (%) ORa (95% CI) P Permutated Pc β HPV Speciesb Any β HPV 56 (70.0) 134 (56.1) 1.84 (1.05–3.23) 0.04 0.199 Any β 1 HPV 41 (51.3) 94 (39.3) 1.74 (1.00–3.04) 0.05 0.296 Any β 2 HPV 42 (52.5) 105 (43.9) 1.34 (0.80–2.25) 0.27 >0.999 Any β 3 HPV 18 (22.5) 34 (14.2) 1.86 (0.95–3.63) 0.07 0.363 Specific β HPV typesb β 1 HPV5 14 (17.5) 27 (11.3) 1.78 (0.85–3.72) 0.13 0.605 β 1 HPV12 6 (7.5) 16 (6.7) 1.11 (0.42–2.93) 0.83 >0.999 β 1 HPV20 14 (17.5) 31 (13.0) 1.42 (0.70–2.91) 0.33 >0.999 β 1 HPV36 10 (12.5) 23 (9.6) 1.13 (0.50–2.55) 0.77 >0.999 Clade of β 1 HPVs 5, 36, 47, & 143 17 (21.3) 39 (16.3) 1.36 (0.71–2.58) 0.35 >0.999 β 1 HPV105 11 (13.8) 20 (8.4) 1.62 (0.72–3.63) 0.24 >0.999 β 1 HPV124 7 (8.8) 20 (8.4) 1.06 (0.42–2.67) 0.90 >0.999 β 2 HPV23 9 (11.3) 17 (7.1) 1.67 (0.70–3.97) 0.24 >0.999 β 2 HPV37 8 (10.0) 21 (8.8) 1.21 (0.49–2.97) 0.68 >0.999 β 2 HPV38 15 (18.8) 34 (14.2) 1.48 (0.75–2.92) 0.26 >0.999 β 2 HPV107 10 (12.5) 19 (8.0) 1.69 (0.72–3.98) 0.23 >0.999 γ HPV speciesb Any γ HPV 32 (40.0) 77 (32.2) 1.53 (0.86–2.70) 0.15 0.668 Any γ 7 HPV 13 (16.3) 34 (14.2) 1.12 (0.54–2.34) 0.76 >0.999 Any γ 8 HPV 4 (5.0) 21 (8.8) 0.43 (0.14–1.36) 0.15 >0.999 Any γ 10 HPV 7 (8.8) 17 (7.1) 1.38 (0.52–3.66) 0.52 >0.999 Any γ 12 HPV 7 (8.8) 13 (5.4) 1.92 (0.72–5.14) 0.19 >0.999 Any γ 15 HPV 8 (10.0) 14 (5.9) 1.93 (0.69–5.42) 0.21 >0.999