Table 1.
Characteristics of HNSCC patients of NICEI-CIH and the Leipzig subsample of TRANSCAN-DietINT constituting the test cohort binary classified based on VEGF in plasma (<26 vs. >26 ng/L) or serum (<264 vs. >264 ng/L). Significant differences between groups (p < 0.05) in Pearson’s Chi-square tests are highlighted bold.
| Characteristics | TC Cohort | VEGF Plasma | VEGF Serum | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| <26 ng/L | >26 ng/L | <264 ng/L | >264 ng/L | ||||||||||
| n | (%) | n | (%) | n | (%) | p Value ‡ | n | (%) | n | (%) | p Value ‡ | ||
| Study | DietINT | 40 | (53.3) | 24 | (61.5) | 16 | (44.4) | 0.1382 | 29 | (56.9) | 11 | (45.8) | 0.3718 |
| NICEI | 35 | (46.7) | 15 | (38.5) | 20 | (55.6) | 22 | (43.1) | 13 | (54.2) | |||
| Sex | female | 11 | (14.7) | 7 | (17.9) | 4 | (11.1) | 0.4030 | 9 | (17.6) | 2 | (8.3) | 0.2875 |
| male | 64 | (85.3) | 32 | (82.1) | 32 | (88.9) | 42 | (82.4) | 22 | (91.7) | |||
| BMI ¶ | 15–24.9 | 36 | (48.0) | 18 | (46.2) | 18 | (50.0) | 0.5578 | 23 | (45.1) | 13 | (54.2) | 0.5227 |
| 25–29.9 | 32 | (42.7) | 16 | (41.0) | 16 | (44.4) | 22 | (43.1) | 10 | (41.7) | |||
| >30 | 7 | (9.3) | 5 | (12.8) | 2 | (5.6) | 6 | (11.8) | 1 | (4.2) | |||
| p16 IHC | negative | 15 | (20.0) | 10 | (25.6) | 5 | (13.9) | 0.4453 | 9 | (18.4) | 6 | (25) | 0.5100 |
| (CINtec+) | positive | 58 | (77.3) | 28 | (71.8) | 30 | (83.3) | 40 | (81.6) | 18 | (75) | ||
| unknown | 2 | (2.7) | 1 | (2.6) | 1 | (2.8) | 2 | (3.9) | -- | (--) | |||
| Number of | 0 | 12 | (16.0) | 7 | (17.9) | 5 | (13.9) | 0.7700 | 8 | (15.7) | 4 | (16.7) | 0.6833 |
| positive | 1–2 | 26 | (34.7) | 14 | (35.9) | 12 | (33.3) | 18 | (35.3) | 8 | (33.3) | ||
| nodes | 3–4 | 23 | (30.7) | 11 | (28.2) | 12 | (33.3) | 15 | (29.4) | 8 | (33.3) | ||
| 5–8 | 10 | (13.3) | 6 | (15.4) | 4 | (11.1) | 6 | (11.8) | 4 | (16.7) | |||
| >8 | 4 | (5.3) | 1 | (2.6) | 3 | (8.3) | 4 | (7.8) | -- | (--) | |||
| Extranodal | negative | 22 | (29.3) | 14 | (35.9) | 8 | (22.2) | 0.4714 | 18 | (35.3) | 4 | (16.7) | 0.4399 |
| extension | positive | 37 | (49.3) | 20 | (51.3) | 17 | (47.2) | 27 | (52.9) | 10 | (41.7) | ||
| unknown | 16 | (21.3) | 5 | (12.8) | 11 | (30.6) | 6 | (11.8) | 10 | (41.7) | |||
| Grading | 1 | 1 | (1.3) | 1 | (2.6) | -- | (--) | 0.242 | 1 | (2.0) | -- | (--) | 0.6376 |
| 2 | 33 | (44.0) | 14 | (35.9) | 19 | (52.8) | 21 | (41.2) | 12 | (50.0) | |||
| 3 | 41 | (54.7) | 24 | (61.5) | 17 | (47.2) | 29 | (56.9) | 12 | (50.0) | |||
| Lymphatic | no | 7 | (9.3) | 3 | (7.7) | 4 | (11.1) | 0.4659 | 4 | (7.8) | 3 | (12.5) | 0.3472 |
| invasion | yes | 54 | (72.0) | 31 | (79.5) | 23 | (63.9) | 40 | (78.4) | 14 | (58.3) | ||
| unknown | 14 | (18.7) | 5 | (12.8) | 9 | (25.0) | 7 | (13.7) | 7 | (29.2) | |||
| Vascular | no | 57 | (76.0) | 31 | (79.5) | 26 | (72.2) | 0.6769 | 41 | (80.4) | 16 | (66.7) | 0.2839 |
| invasion | yes | 3 | (4.0) | 2 | (5.1) | 1 | (2.8) | 3 | (5.9) | -- | (--) | ||
| unknown | 15 | (20.0) | 6 | (15.4) | 9 | (25.0) | 7 | (13.7) | 8 | (33.3) | |||
| Perineural | no | 51 | (68.0) | 30 | (76.9) | 21 | (58.3) | 0.1564 | 38 | (74.5) | 13 | (54.2) | 0.6237 |
| invasion | yes | 9 | (12.0) | 3 | (7.7) | 6 | (16.7) | 6 | (11.8) | 3 | (12.5) | ||
| unknown | 15 | (20.0) | 6 | (15.4) | 9 | (25.0 | 7 | (13.7) | 8 | (33.3) | |||
| Any soft risk | no | 5 | (6.7) | 3 | (7.7) | 2 | (5.6) | 0.8144 | 3 | (5.9) | 2 | (8.3) | 0.4813 |
| factor | yes | 55 | (73.3) | 30 | (76.9) | 25 | (69.4) | 41 | (80.4) | 14 | (58.3) | ||
| unknown | 15 | (20.0) | 6 | (15.4) | 9 | (25.0) | 7 | (13.7) | 8 | (33.3) | |||
| T category | T1 | 9 | (12.0) | 6 | (15.4) | 3 | (8.3) | 0.4759 | 7 | (13.7) | 2 | (8.3) | 0.1460 |
| TNM 2017 | T2 | 28 | (37.3) | 15 | (38.5) | 13 | (36.1) | 19 | (37.3) | 9 | (37.5) | ||
| T3 | 24 | (32.0) | 13 | (33.3) | 11 | (30.6) | 19 | (37.3) | 5 | (20.8) | |||
| T4 | 12 | (16.0) | 4 | (10.3) | 8 | (22.2) | 5 | (9.8) | 7 | (29.2) | |||
| T4a | 1 | (1.3) | -- | (--) | 1 | (2.8) | -- | (--) | 1 | (4.2) | |||
| Tx | 1 | (1.3) | 1 | (2.6) | -- | (--) | 1 | (2.0) | -- | (--) | |||
| N category | 0 | 15 | (20.0) | 9 | (23.1) | 6 | (16.7) | 0.7821 | 10 | (19.6) | 5 | (20.8) | 0.7048 |
| TNM 2017 | 1 | 23 | (30.7) | 13 | (33.3) | 10 | (27.8) | 19 | (37.3) | 4 | (16.7) | ||
| 2 | 21 | (28.0) | 8 | (20.5) | 13 | (36.1) | 12 | (23.5) | 9 | (37.5) | |||
| 2a | 3 | (4.0) | 2 | (5.1) | 1 | (2.8) | 2 | (3.9) | 1 | (4.2) | |||
| 2c | 3 | (4.0) | 2 | (5.1) | 1 | (2.8) | 2 | (3.9) | 1 | (4.2) | |||
| 3a | 3 | (4.0) | 1 | (2.6) | 2 | (5.6) | 2 | (3.9) | 1 | (4.2) | |||
| 3b | 7 | (9.3) | 4 | (10.3) | 3 | (8.3) | 4 | (7.8) | 3 | (12.5) | |||
| M category | 0 | 72 | (96.0) | 38 | (97.4) | 34 | (94.4) | 0.5089 | 50 | (98.0) | 22 | (91.7) | 0.1889 |
| TNM 2017 | 1 | 3 | (4.0) | 1 | (2.6) | 2 | (5.6) | 1 | (2.0) | 2 | (8.3) | ||
| UICC 2017 | I | 20 | (26.7) | 10 | (25.6) | 10 | (27.8) | 0.6652 | 15 | (29.4) | 5 | (20.8) | 0.6624 |
| II | 17 | (22.7) | 11 | (28.2) | 6 | (16.7) | 13 | (25.5) | 4 | (16.7) | |||
| III | 22 | (29.3) | 9 | (23.1) | 13 | (36.1) | 14 | (27.5) | 8 | (33.3) | |||
| IV | 3 | (4.0) | 1 | (2.6) | 2 | (5.6) | 1 | (2.0) | 2 | (8.3) | |||
| IVA | 6 | (8.0) | 4 | (10.3) | 2 | (5.6) | 4 | (7.8) | 2 | (8.3) | |||
| IVB | 7 | (9.3) | 4 | (10.3) | 3 | (8.3) | 4 | (7.8) | 3 | (12.5) | |||
| Received | no OP | 16 | (21.3) | 6 | (15.4) | 10 | (27.8) | 0.1906 | 7 | (13.7) | 9 | (37.5) | 0.0191 |
| surgery | OP | 59 | (78.7) | 33 | (84.6) | 26 | (72.2) | 44 | (86.3) | 15 | (62.5) | ||
| Received | no RT | 7 | (9.3) | 2 | (5.1) | 5 | (13.9) | 0.1926 | 4 | (7.8) | 3 | (12.5) | 0.5178 |
| radiotherapy | RT | 68 | (90.7) | 37 | (94.9) | 31 | (86.1) | 47 | (92.2) | 21 | (87.5) | ||
| Received | no RChT | 29 | (38.7) | 15 | (38.5) | 14 | (38.9) | 0.9697 | 22 | (43.1) | 7 | (29.2) | 0.2465 |
| RChT | RChT | 46 | (61.3) | 24 | (61.5) | 22 | (61.1) | 29 | (56.9) | 17 | (70.8) | ||
| Event-free | no event | 53 | (70.7) | 33 | (84.6) | 20 | (55.6) | 0.0048 | 38 | (74.5) | 15 | (62.5) | 0.2866 |
| survival | event | 22 | (29.3) | 6 | (15.4) | 16 | (44.4) | 13 | (25.5) | 9 | (37.5) | ||
| Progression- | no event | 55 | (73.3) | 33 | (84.6) | 22 | (61.1) | 0.0215 | 38 | (74.5) | 17 | (70.8) | 0.7370 |
| free survival | event | 20 | (26.7) | 6 | (15.4) | 14 | (38.9) | 13 | (25.5) | 7 | (29.2) | ||
| Local control | no event | 62 | (82.7) | 35 | (89.7) | 27 | (75.0) | 0.0920 | 43 | (84.3) | 19 | (79.2) | 0.5828 |
| event | 13 | (17.3) | 4 | (10.3) | 9 | (25.0) | 8 | (15.7) | 5 | (20.8) | |||
| Nodal | no event | 62 | (82.7) | 36 | (92.3) | 26 | (72.2) | 0.0217 | 43 | (84.3) | 19 | (79.2) | 0.5828 |
| control | event | 13 | (17.3) | 3 | (7.7) | 10 | (27.8) | 8 | (15.7) | 5 | (20.8) | ||
| Distant | no event | 67 | (89.3) | 37 | (94.9) | 30 | (83.3) | 0.1058 | 45 | (88.2) | 22 | (91.7) | 0.6534 |
| control | event | 8 | (10.7) | 2 | (5.1) | 6 | (16.7) | 6 | (11.8) | 2 | (8.3) | ||
| Loco-regional | no event | 58 | (77.3) | 34 | (87.2) | 24 | (66.7) | 0.0340 | 41 | (80.4) | 17 | (67.8) | 0.3564 |
| control | event | 17 | (22.7) | 5 | (12.8) | 12 | (33.1) | 10 | (19.6) | 7 | (29.2) | ||
| Overall | alive | 67 | (89.3) | 35 | (89.7) | 32 | (88.9) | 0.9046 | 47 | (92.2) | 20 | (83.3) | 0.2482 |
| survival | dead | 8 | (10.7) | 4 | (10.3) | 4 | (11.1) | 4 | (7.8) | 4 | (16.7) | ||
‡ p value from Pearson’s Chi square (χ2) tests. ¶ Classification of anthropometric height/weight characteristics according to WHO (2000) “Obesity: Preventing and Managing the Global Epidemic” into underweight (BMI 15–19.9 kg/m2) and normal weight (BMI 20–24.9 kg/m2); overweight (BMI 25–29.9 kg/m2); obesity summarizing adiposity I (BMI 30–34.9 kg/m2), adiposity II (BMI 35–39.9 kg/m2), and adiposity III (BMI ≥ 40 kg/m2). p16 IHC (CINtec+), combined immunohistochemical tests for p16INK4A and Ki-67 expression; T, Tumor size; N, Nodal involvement; M, distant metastasis; UICC, Union for International Cancer Control; OP, surgical operation of the primary and/or neck dissection; RT, radiotherapy; RChT, radio-chemo-therapy.