Table 2.
Frequencies and linkage disequilibrium (D) and relative linkage disequilibrium (Drel ) in a large German sample of healthy blood donors (23) and HPV-driven head and neck squamous cell carcinoma (HNSCC; this study) accompanied by expected frequencies of HLA diplotypes and triplotypes significantly deviating from antigen-based haplotype frequencies in blood donors (23) and odds ratio (OR) and 95% confidence interval (95% CI) as well as two-sided p-value (p-value † ), Benjamini–Hochberg corrected p-value (p-value †† ) (25), and false-positive reporting probability (FPRP) (26) in HPV-driven HNSCC patients.
| f observed I | Dab I | Dab (rel) I | f observed rel. to f expected I | Dab = fab -fafb II | Dab (rel) II | f observed rel. to f expected in HNSCC II | Δ f observed in HNSCC | RR diplotype carrier | RR diplotype non-carrier |
f observed
in HNSCC n (%) |
f expected |
in healthy adults n (%) |
OR (95% CI) | p-value † | p-value †† | FPRP level ‡ | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A2-B62 | 0.042 | 0.019 | 0.172 | 1.819 | −0.0005 | −0.0408 | 0.9592 | −0.8601 | 0.2515 | 3.9762 | 4 (1.1) | 15.9 (4.2) | 0.243 (0.081 –0.736) | 0.0123 | >0.999 | 0.3573 |
| A1-B8 | 0.083 | 0.066 | 0.519 | 4.925 | 0.0227 | 0.1925 | 2.5653 | −2.3599 | 0.4489 | 2.2278 | 14 (3.7) | 31.2 (8.3) | 0.428 (0.224 –0.817) | 0.0101 | >0.999 | 0.1828 |
| B44-DR7 | 0.030 | 0.015 | 0.105 | 1.954 | −0.0005 | −0.0600 | 0.9400 | −1.0141 | 0.2662 | 3.7562 | 3 (0.8) | 11.3 (3.0) | 0.260 (0.072 –0.938) | 0.0396 | >0.999 | 0.7191 |
| B62-DR4 | 0.029 | 0.019 | 0.209 | 2.805 | 0.0023 | 0.0473 | 1.4100 | −1.3946 | 0.2735 | 3.6560 | 3 (0.8) | 11.0 (2.9) | 0.268 (0.074 –0.968) | 0.0444 | >0.999 | 0.7473 |
| A1-B8-DR3 | 0.062 | 0.053 | 0.567 | 6.644 | 0.0154 | 0.3796 | 5.8750 | −0.7687 | 0.2981 | 3.3545 | 14 (1.9) | 47.0 (6.2) | 0.285 (0.155 –0.522) | 0.0001 | 0.0042 | 0.0014 |
| A2-B7-DR15 | 0.022 | 0.016 | 0.379 | 3.852 | 0.0013 | 0.0375 | 1.3147 | −2.5375 | 0.2387 | 4.1886 | 4 (0.5) | 16.8 (2.2) | 0.235 (0.078 –0.702) | 0.0095 | 0.8074 | 0.4546 |
| A2-B60-DR13 | 0.011 | 0.008 | 0.236 | 3.272 | −0.0010 | −0.4303 | 0.5697 | −2.7027 | 0.1201 | 8.3246 | 1 (0.1) | 8.3 (1.1) | 0.119 (0.015 –0.949) | 0.0445 | >0.999 | 0.8883 |
| A2-B62-DR4 | 0.018 | 0.013 | 0.258 | 3.229 | 0.0012 | 0.1015 | 1.8800 | −1.3488 | 0.1458 | 6.8582 | 2 (0.3) | 13.7 (1.8) | 0.144 (0.032 –0.635) | 0.0105 | 0.8827 | 0.5308 |
| A3-B7-DR15 | 0.034 | 0.025 | 0.372 | 3.802 | 0.0147 | 0.2638 | 3.2137 | −0.5886 | 0.6192 | 1.6149 | 16 (2.1) | 25.8 (3.4) | 0.611 (0.325 –1.149) | 0.1264 | >0.999 | 0.8766 |
| A3-B35-DR1 | 0.017 | 0.014 | 0.399 | 5.029 | 0.0014 | 0.0572 | 1.5326 | −3.4965 | 0.2351 | 4.2538 | 3 (0.4) | 12.8 (1.7) | 0.232 (0.066 –0.819) | 0.0232 | >0.999 | 0.7292 |
| A29-B44-DR7 | 0.009 | 0.007 | 0.481 | 5.383 | −0.0003 | −1.0000 | 0.0000 | −5.3834 | 0.0000 | – | 0 (0.0) | 6.6 (0.9) | 0.070 (0.006 –0.769)¶ | 0.0297 | >0.999 | 0.8700 |
| A24-B8-DR3 | 0.001 | −0.011 | −0.929 | 0.071 | 0.0093 | 0.5321 | 7.8333 | 7.7618 | 12.228 | 0.0818 | 8 (1.1) | 0.7 (0.1) | 12.35 (0.991 –153.8) | 0.0508 | >0.999 | 0.9915 |
| All other A3-triplotypes | 0.019 | 45 (3.0) | 14.3 (1.9) | 3.293 (1.799 –6.027) | 0.0001 | 0.0096 | 0.0114 | |||||||||
| A3-B18 | 0.004 | 11 (0.7) | 2.9 (0.4) | 3.831 (1.047 –14.02) | 0.0424 | >0.999 | 0.9563 | |||||||||
| A3-B44 | 0.006 | 12 (0.8) | 4.4 (0.6) | 2.751 (0.919 –8.235) | 0.0705 | >0.999 | 0.9598 | |||||||||
| A3-B51 | 0.005 | 10 (0.7) | 3.4 (0.5) | 2.962 (0.862 –10.17) | 0.0846 | >0.999 | 0.9738 | |||||||||
| A3-B8 | 0.005 | 12 (0.8) | 3.5 (0.5) | 3.427 (1.043 –11.26) | 0.0424 | >0.999 | 0.9472 | |||||||||
| A1-B51 and A3-B51 |
0.007 | 16 (1.1) | 5.6 (0.7) | 2.916 (1.105 –7.692) | 0.0306 | >0.999 | 0.8913 |
| Frequencies in healthy blood donors according to Müller et al. (23); Dab = fab–fafb, absolute linkage disequilibrium of antigens a and b; Dab (rel), relative linkage disequilibrium of antigens a and b; | Frequencies in this cohort; RR diplotype carrier, relative risk for HNSCC according to ratio of HNSCC versus healthy adults in diplotype carriers; RR diplotype non-carrier, relative risk for HNSCC according to ratio of HNSCC versus healthy adults in diplotype non-carriers; OR (95% CI), odds ratio (95% confidence interval); † p-value from Pearson’s Chi-square (χ2) test; †† Benjamini–Hochberg-corrected p-value from χ2 tests (25); ‡ False-positive reporting probability (FPRP) according to Wacholder et al., 2004 (26); ¶ odds ratio corrected according to Cox by adding 1 to each cell preventing division by zero. Significant p values < 0.05 shown bold.