Table 1.
Distribution of key clinical and etiological variables between MethylMix subtypes.
| MethylMix subtype |
||||||
|---|---|---|---|---|---|---|
| Non-CIMP-Atypical (N = 150) | NSD1-Smoking (N = 80) | CIMP-Atypical (n = 114) | HPV + (N = 64) | Stem-like-Smoking (N = 120) | ||
| Smoking status (n (%)) | Never | 34 (29%) | 6 (10%) | 28 (29%) | 18 (39%) | 10 (11%) |
| Former > 15 years | 17 (15%) | 6 (10%) | 24 (25%) | 5 (11%) | 11 (12%) | |
| Former < 15 years | 32 (27%) | 16 (27%) | 17 (18%) | 12 (26%) | 33 (35%) | |
| Current | 34 (29%) | 31 (53%) | 27 (28%) | 11 (24%) | 39 (42%) | |
| p-Valuesa | 0.162 | < 0.001 | – | 0.775 | < 0.001 | |
| HPV status (n (%)) | HPV − | 81 (99%) | 44 (100%) | 63 (98%) | 1 (3%) | 72 (92%) |
| HPV16 | 0 (0%) | 0 (0%) | 0 (0%) | 32 (89%) | 5 (6%) | |
| HPV33 | 1 (1%) | 0 (0%) | 1 (2%) | 3 (8%) | 1 (1%) | |
| p-Valuesb | 1 | 1 | – | < 0.001 | 0.197 | |
| Gender (n (%)) | F | 45 (37%) | 12 (20%) | 42 (43%) | 5 (11%) | 18 (19%) |
| M | 77 (63%) | 49 (80%) | 56 (57%) | 41 (89%) | 77 (81%) | |
| p-Valuesc | 0.446 | 0.005 | – | < 0.001 | < 0.001 | |
| Anatomic subsite (n (%)) | Base of tongue | 4 (3%) | 2 (3%) | 1 (1%) | 11 (24%) | 4 (4%) |
| Hypopharynx | 2 (2%) | 0 (0%) | 1 (1%) | 1 (2%) | 2 (2%) | |
| Larynx | 15 (12%) | 27 (44%) | 7 (7%) | 1 (2%) | 44 (46%) | |
| Lip | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (1%) | |
| Oral | 94 (77%) | 31 (51%) | 89 (91%) | 8 (17%) | 44 (46%) | |
| Tonsil | 6 (5%) | 1 (2%) | 0 (0%) | 25 (54%) | 0 (0%) | |
| p-Valuesd | 0.011 | < 0.001 | – | < 0.001 | < 0.001 | |
| Pathological grade (n (%)) | 1 | 15 (12%) | 5 (8%) | 20 (21%) | 1 (2%) | 5 (6%) |
| 2 | 82 (68%) | 39 (65%) | 59 (61%) | 15 (37%) | 60 (67%) | |
| 3 | 23 (19%) | 16 (27%) | 18 (19%) | 19 (46%) | 24 (27%) | |
| 4 | 0 (0%) | 0 (0%) | 0 (0%) | 6 (15%) | 1 (1%) | |
| p-Valuese | 0.152 | 0.069 | – | 0.014 | 0.005 | |
| Age (mean (IQR)) p-valuef | 61 (52–70) p = 0.406 | 58 (52–65) p = 0.016 | 63 (53–73) | 56 (50–62) p = 0.002 | 63 (56–68) p = 0.947 | |
| Overall mutation burden (mean (IQR)) p-valuef | 124 (62–115) p = 0.08 | 188 (97–252) p = 0.004 | 114 (695–145) | 99 (38–117) p = 0.004 | ||
| Smoking mutation rates (mean (IQR)) p-valuef | G > T transversions | 7 (3–9) p = 0.574 | 24 (6–34) p ≤ 0.001 | 6 (3–8) | 5 (2–5) p = 0.037 | 17 (5–20) p ≤ 0.001 |
| C > A transversions | 7 (3–8) p = 0.875 | 25 (6–36) p ≤ 0.001 | 7 (4–9) | 4 (1–7) p = 0.003 | 17 (5–21) p = 0.002 | |
| # CNAs (mean (IQR)) p-valuef | CNAScore | 10,420 (6145–14,060) p ≤ 0.001 | 11,850 (8055–15,560) p ≤ 0.001 | 6805 (2550–9738) | 6838 (3886–8006) p = 0.294 | 11,550 (8476–15,680) p ≤ 0.001 |
| Xenobiotic metabolism expression (mean (IQR)) p-valuef | − 0.3 (− 0.8–0.1) p ≤ 0.001 | 0.8 (0.2–1.3) p ≤ 0.001 | 0 | 0.2 (− 0.2–0.6) p ≤ 0.001 | 0.6 (0.1–1.2) p ≤ 0.001 | |
| Abnormally methylated genes (mean (IQR)) p-valuef | # hyper genes | 954 (878–1033) p ≤ 0.001 | 724 (621–804) p ≤ 0.001 | 1282 (1184–1362) | 866 (736–943) p ≤ 0.001 | 760 (674–850) p ≤ 0.001 |
| # hypo genes | 422 (384–461) p ≤ 0.001 | 587 (542–627) p ≤ 0.001 | 370 (344–394) | 462 (424–496) p ≤ 0.001 | 439 (380–494) p ≤ 0.001 | |
| IFN gene expression (mean (IQR)) p-valuef | 0.2 (− 0.4–0.9) p ≤ 0.001 | − 0.4 (− 1.1–0.4) p ≤ 0.001 | 0.8 (0.3–1.3) | − 0.2 (− 0.5–0.3) p ≤ 0.001 | − 0.6 (− 1.2–0.1) p ≤ 0.001 | |
Pearson chi-squared test for difference in distribution of non-smokers (never or former > 15 years) between CIMP-Atypical subtype and other subtypes.
Pearson chi-squared test for difference in distribution of HPV − patients between CIMP-Atypical subtype and other subtypes.
Pearson chi-squared test for difference in distribution of female patients between CIMP-Atypical subtype and other subtypes.
Pearson chi-squared test for difference in distribution of OSCC patients between CIMP-Atypical subtype and other subtypes.
Pearson chi-squared test for difference in distribution of grade 1 cancers between CIMP-Atypical subtype and other subtypes.
Wilcoxon rank sum test for mean difference in continuous variable between CIMP-Atypical subtype and other subtypes.