Table 2.
Subgroup analysis of relationship between EBV infection and OS/FFS/PFS/EFS/DSS.
| Outcome | Subgroup | Data set (n) | Patients (n) | Model | HR (95%CI) | P | Heterogeneity | |
|---|---|---|---|---|---|---|---|---|
| I2 | Ph | |||||||
| OS | ALL | 36 | 7213 | Fixed | 1.443 (1.250-1.666) | <0.001 | 43.7% | 0.003 |
| Continent | Fixed | |||||||
| Asia | 15 | 2057 | 1.658 (1.205-2.282) | 0.002 | 0 | 0.696 | ||
| Europe | 11 | 2875 | 1.321 (1.065-1.638) | 0.011 | 51.4% | 0.024 | ||
| Africa | 3 | 255 | 0.408 (0.147-1.129) | 0.084 | 74.9% | 0.019 | ||
| South America | 1 | 97 | 1.170 (0.078-17.452) | 0.909 | – | – | ||
| North America | 4 | 1233 | 1.572 (1.209-2.045) | 0.001 | 78.8% | 0.003 | ||
| Australia | 1 | 119 | 2.340 (0.819-6.684) | 0.112 | – | – | ||
| Unclassified | 1 | 577 | 1.830 (0.471-7.108) | 0.383 | – | – | ||
| Histology | ||||||||
| HL | 18 | 2889 | 1.501 (1.151-1.958) | 0.003 | 55.1% | 0.003 | ||
| cHL | 18 | 4324 | 1.420 (1.197-1.684) | <0.001 | 29.7% | 0.114 | ||
| Detection method | Fixed | |||||||
| EBER | 12 | 1606 | 2.024 (1.551-2.642) | <0.001 | 0 | 0.749 | ||
| LMP1 | 11 | 2409 | 1.506 (1.121-2.022) | 0.007 | 51.6% | 0.024 | ||
| EBER/LMP1 | 13 | 2363 | 1.147 (0.930-1.414) | 0.200 | 47.9% | 0.027 | ||
| Data source | Fixed | |||||||
| Univariate | 27 | 4247 | 1.599 (1.328-1.926) | <0.001 | 39.2% | 0.021 | ||
| Multivariate | 9 | 2131 | 1.240 (0.989-1.555) | 0.062 | 51.7% | 0.035 | ||
| Data extraction | Fixed | |||||||
| K-M curve | 21 | 3389 | 1.740 (1.380-2.195) | <0.001 | 34.6% | 0.061 | ||
| Direct | 15 | 2989 | 1.285 (1.070-1.543) | 0.007 | 49.2% | 0.016 | ||
| Age subgroups | 11 | Random | 1.080 (0.657-1.776) | 0.762 | 62.9% | 0.003 | ||
| children and adolescent | 4 | 330 | 0.296 (0.085-1.034) | 0.056 | 41.4% | 0.163 | ||
| young adults | 4 | 995 | 0.882 (0.518-1.500) | 0.642 | 0 | 0.882 | ||
| older adults | 3 | 480 | 1.905 (1.380-2.629) | <0.001 | 23% | 0.273 | ||
| FFS | ALL | 9 | 3399 | Fixed | 1.030 (0.832-1.274) | 0.788 | 0 | 0.556 |
| Detection method | Fixed | |||||||
| EBER | 4 | 685 | 0.961 (0.723-1.277) | 0.785 | 35.7% | 0.198 | ||
| LMP1 | 4 | 1538 | 1.158 (0.821-1.632) | 0.403 | 0 | 0.703 | ||
| EBER/LMP1 | 1 | 190 | 0.910 (0.361-2.295) | 0.842 | – | – | ||
| Data source | Fixed | |||||||
| Univariate | 7 | 1728 | 1.168 (0.891-1.529) | 0.261 | 0 | 0.920 | ||
| Multivariate | 2 | 685 | 0.836 (0.591-1.183) | 0.312 | 61.7% | 0.106 | ||
| Data extraction | Fixed | |||||||
| K-M curve | 6 | 1728 | 1.158 (0.853-1.573) | 0.346 | 0 | 0.852 | ||
| Direct | 3 | 685 | 0.921 (0.685-1.240) | 0.589 | 46.4% | 0.155 | ||
| Age subgroups | Fixed | 1.487 (0.947-2.337) | 0.085 | 36.0% | 0.154 | |||
| children and adolescent | 1 | 58 | 0.910 (0.171-4.851) | 0.912 | – | – | ||
| young adults | 4 | 353 | 1.000 (0.563-1.775) | 1.000 | 0 | 0.733 | ||
| older adults | 2 | 128 | 3.726 (1.649-8.419) | 0.002 | 3.9% | 0.308 | ||
| PFS | ALL | 5 | 736 | Random | 1.365 (0.694-2.684) | 0.368 | 54.5% | 0.066 |
| EFS | ALL | 10 | 1477 | Fixed | 0.962 (0.755-1.227) | 0.756 | 0 | 0.543 |
| Continent | Fixed | |||||||
| Asia | 3 | 426 | 1.087 (0.710-1.664) | 0.702 | 65.5% | 0.055 | ||
| Africa | 1 | 131 | 0.720 (0.228-2.277) | 0.576 | – | – | ||
| Europe | 3 | 543 | 0.937 (0.677-1.298) | 0.697 | 0 | 0.400 | ||
| South America | 4 | 377 | 0.816 (0.332-2.005) | 0.657 | 0 | 0.906 | ||
| Detection method | Fixed | |||||||
| EBER | 3 | 368 | 1.238 (0.805-1.902) | 0.331 | 0 | 0.528 | ||
| LMP1 | 2 | 298 | 0.731 (0.346-1.548) | 0.413 | 74.9% | 0.046 | ||
| EBER/LMP1 | 6 | 811 | 0.880 (0.638-1.212) | 0.432 | 0 | 0.913 | ||
| Data source | Fixed | |||||||
| Univariate | 10 | 1288 | 1.018 (0.794-1.307) | 0.886 | 0 | 0.839 | ||
| Multivariate | 1 | 189 | 0.330 (0.112-0.975) | 0.045 | – | – | ||
| Data extraction | Fixed | |||||||
| K-M curve | 7 | 687 | 1.039 (0.595-1.815) | 0.893 | 0 | 0.881 | ||
| Direct | 4 | 790 | 0.945 (0.721-1.238) | 0.682 | 53.2% | 0.093 | ||
| DSS | ALL | 8 | 2061 | Fixed | 2.312 (1.799-2.972) | <0.001 | 26% | 0.221 |
| Continent | ||||||||
| Asia | 2 | 483 | 2.120 (1.315-3.418) | 0.002 | 71.7% | 0.060 | ||
| Europe | 3 | 656 | 2.629 (1.738-3.977) | <0.001 | 0 | 0.999 | ||
| North America | 3 | 922 | 2.165 (1.420-3.300) | <0.001 | 62.5% | 0.069 | ||
| Detection method | Fixed | |||||||
| EBER | 3 | 920 | 2.334 (1.644-3.313) | <0.001 | 48.3% | 0.144 | ||
| LMP1 | 1 | 102 | 2.660 (1.099-6.436) | 0.030 | – | – | ||
| EBER/LMP1 | 4 | 1039 | 2.223 (1.499-3.297) | <0.001 | 45.0% | 0.142 | ||
| Data source | Fixed | |||||||
| Univariate | 7 | 1902 | 2.189 (1.686-2.844) | <0.001 | 18.1% | 0.292 | ||
| Multivariate | 1 | 159 | 4.396 (1.792-10.785) | 0.001 | – | – | ||
| Data extraction | Fixed | |||||||
| K-M curve | 5 | 1542 | 2.504 (1.859-3.373) | <0.001 | 0 | 0.978 | ||
| Direct | 3 | 519 | 1.902 (1.192-3.033) | 0.007 | 75.2% | 0.018 | ||
| Age subgroups | Fixed | 2.094 (1.506-2.912) | <0.001 | 1.2% | 0.415 | |||
| children and adolescent | 1 | 36 | 0.180 (0.020-1.660) | 0.130 | – | – | ||
| young adults | 2 | 845 | 1.744 (0.736-4.131) | 0.206 | 0 | 0.965 | ||
| older adults | 4 | 501 | 2.308 (1.607-3.312) | <0.001 | 0 | 0.817 | ||
EBV, Epstein–Barr virus; HL, Hodgkin’s lymphoma; cHL, classical Hodgkin lymphoma; HR, hazard ratios, EBER, Epstein–Barr virus-encoded small RNA; LMP1, latent membrane protein-1; OS, Overall survival; FFS, Failure-free survival; PFS, Progression-free survival; EFS, Event-free survival; DSS, Disease-specific survival; K-M curve, Kaplan-Meier curve.