Table 1.
All | HPV-negative | HPV16-driven | P value | p16INK4a negative HPV16–DNA-positive | p16INK4a positive HPV–DNA-negative | |
---|---|---|---|---|---|---|
(N = 620) | (N = 436) | (N = 184) | (N = 29) | (N = 39) | ||
Risk factors | N (%)* | N (%) | N (%) | N (%) | N (%) | |
Gender | ||||||
Male | 478 (77) | 340 (78) | 138 (75) | 0.420 | 23 (79) | 32 (82) |
Female | 142 (23) | 96 (22) | 46 (25) | 6 (21) | 7 (18) | |
Age (IQR) | ||||||
Median | 60.8 | 60.0 | 62.6 | 0.002§ | 57.9 | 60.0 |
Third quartile | 67.8 | 66.4 | 71.6 | 65.2 | 64.9 | |
First quartile | 53.9 | 53.8 | 54.1 | 53.4 | 56.0 | |
Comorbidity (ECOG) | ||||||
0 | 38 (6) | 21 (5) | 17 (9) | 0.008# | 4 (14) | 2 (5) |
1 | 398 (65) | 277 (64) | 121 (67) | 17 (61) | 26 (67) | |
2 | 152 (25) | 114 (26) | 38 (21) | 4 (14) | 9 (23) | |
3 | 22 (4) | 17 (4) | 5 (3) | 3 (11) | 2 (5) | |
4 | 5 (1) | 5 (1) | 0 (0) | 0 (0) | 0 (0) | |
Unknown | 5 | 2 | 3 | 1 | 0 | |
Healthy (0–1) | 436 (71) | 298 (69) | 138 (76) | 0.059 | 21 (75) | 28 (72) |
Sick (2–4) | 179 (29) | 136 (31) | 43 (24) | 7 (25) | 11 (28) | |
Alcohol | ||||||
>2 standard drinks/day | 292 (53) | 269 (68) | 23 (15) | <0.001 | 20 (77) | 15 (44) |
≤2 standard drinks/ day | 260 (47) | 125 (32) | 135 (85) | 6 (23) | 19 (56) | |
Unknown | 68 | 42 | 26 | 3 | 5 | |
Smoking | ||||||
Yes | 489 (81) | 392 (92) | 97 (56) | <0.001 | 26 (90) | 31 (82) |
No | 112 (19) | 36 (8) | 76 (44) | 3 (10) | 7 (18) | |
Unknown | 19 | 8 | 11 | 0 | 1 | |
Pack years (IQR) | ||||||
Median | 38.0 | 40.0 | 25.5 | <0.001§ | 40.0 | 33.0 |
Third quartile | 50.0 | 52.5 | 40.0 | 61.5 | 43.5 | |
First quartile | 25.0 | 29.8 | 15.0 | 30.0 | 25.5 | |
Smokers (N), pack year unspecified | 76 | 60 | 16 | 5 | 4 | |
Tumour characteristics | ||||||
Localisation | ||||||
Tonsil | 259 (42) | 150 (34) | 109 (59) | <0.001 | 12 (41) | 17 (44) |
Other than tonsil | 361 (58) | 286 (66) | 75 (41) | 17 (59) | 22 (56) | |
T stage | ||||||
1–2 | 319 (52) | 202 (47) | 117 (64) | <0.001 | 10 (34) | 23 (59) |
3–4 | 297 (48) | 230 (53) | 67 (36) | 19 (66) | 16 (41) | |
1 | 137 (22) | 93 (22) | 44 (24) | <0.001# | 8 (28) | 8 (21) |
2 | 182 (30) | 109 (25) | 73 (40) | 2 (7) | 15 (38) | |
3 | 128 (21) | 98 (23) | 30 (16) | 9 (31) | 7 (18) | |
4 | 36 (6) | 24 (6) | 12 (7) | 0 (0) | 1 (3) | |
4a | 56 (9) | 41 (9) | 15 (8) | 6 (21) | 3 (8) | |
4b | 77 (13) | 67 (16) | 10 (5) | 4 (14) | 5 (13) | |
Unknown | 4 | 4 | 0 | 0 | 0 | |
N stage | ||||||
N0 | 157 (26) | 134 (31) | 23 (13) | <0.001 | 11 (38) | 7 (18) |
N+ | 455 (74) | 295 (69) | 160 (87) | 18 (62) | 31 (82) | |
N0 | 157 (26) | 134 (31) | 23 (13) | 0.630# | 11 (38) | 7 (18) |
N1 | 106 (17) | 53 (12) | 53 (29) | 1 (3) | 6 (16) | |
N2–N2a | 62 (10) | 34 (8) | 28 (15) | 2 (7) | 3 (8) | |
N2b | 187 (31) | 129 (30) | 58 (32) | 8 (28) | 14 (37) | |
N2c | 75 (12) | 59 (14) | 16 (9) | 4 (14) | 7 (18) | |
N3 | 25 (4) | 20 (5) | 5 (3) | 3 (10) | 1 (3) | |
Unknown | 8 | 7 | 1 | 0 | 1 | |
M stage | ||||||
M0 | 561 (93) | 396 (93) | 165 (93) | 0.985 | 25 (89) | 35 (92) |
M+ | 44 (7) | 31 (7) | 13 (7) | 3 (11) | 3 (8) | |
Unknown | 15 | 9 | 6 | 1 | 1 | |
UICC7 stages | ||||||
I–III | 218 (36) | 152 (35) | 66 (36) | 0.881 | 10 (34) | 13 (33) |
>III | 394 (64) | 277 (65) | 117 (64) | 19 (66) | 26 (67) | |
I | 52 (8) | 47 (11) | 5 (3) | 0.277# | 7 (24) | 1 (3) |
II | 53 (9) | 43 (10) | 10 (5) | 1 (3) | 6 (15) | |
III | 113 (18) | 62 (14) | 51 (28) | 2 (7) | 6 (15) | |
IV–IVa | 268 (44) | 177 (41) | 91 (50) | 12 (41) | 18 (46) | |
IVb | 83 (14) | 71 (17) | 12 (7) | 4 (14) | 5 (13) | |
IVc | 43 (7) | 29 (7) | 14 (8) | 3 (10) | 3 (8) | |
Unknown | 8 | 7 | 1 | 0 | 0 | |
UICC-8 stages | ||||||
I–III | 306 (54) | 149 (37) | 157 (91) | <0.001 | 12 (43) | 12 (32) |
>III | 265 (46) | 249 (63) | 16 (9) | 16 (57) | 25 (68) | |
I | 123 (22) | 45 (11) | 78 (45) | <0.001# | 8 (29) | 6 (16) |
II | 90 (16) | 43 (11) | 47 (27) | 1 (4) | 4 (11) | |
III | 93 (16) | 61 (15) | 32 (18) | 3 (11) | 2 (5) | |
IV–IVa | 174 (30) | 158 (40) | 16 (9) | 11 (39) | 18 (49) | |
IVb | 70 (12) | 70 (18) | 0 (0) | 3 (11) | 5 (14) | |
IVc | 21 (4) | 21 (5) | 0 (0) | 2 (7) | 2 (5) | |
Unknown | 49 | 38 | 11 | 1 | 2 | |
Palliative treatment | 43 (7) | 35 (8) | 8 (5) | 0.091 | 2 (7) | 0 |
Curative treatment type | ||||||
Upfront surgery without neck dissection | 39 (7) | 31 (8) | 8 (5) | 0.022 | 5 (17) | 1 (3) |
Upfront surgery with neck dissection | 325 (54) | 210 (54) | 115 (68) | 17 (59) | 20 (53) | |
Definitive radiotherapy | 25 (4) | 20 (5) | 5 (3) | 0 (0) | 2 (5) | |
Definitive chemo–radiotherapy | 167 (28) | 126 (33) | 41 (24) | 5 (17) | 15 (39) | |
Unknown | 21 | 14 | 7 | 0 | 1 | |
Resection status of surgery | ||||||
R0 | 268 (79) | 177 (79) | 91 (81) | 0.690 | 17 (77) | 17 (81) |
R+ | 70 (21) | 48 (21) | 22 (19) | 5 (23) | 4 (19) | |
Unknown | 26 | 16 | 10 | 0 | 0 |
OPSCC patients with discordant HPV–DNA and p16INK4a tests (N = 68) are indicated for comparison.
*Percentage based on total cases (N = 620) without missing values. P values for comparison of HPV-negative versus HPV16-driven OPSCC (asymptotic, two-sided) calculated by chi square, (§) t test or (#) Mantel–Haenszel test of trend; significant P values (P ≤ 0.05) in bold.