Table 4.
Stratified Cox Proportional Hazards Analysis comparing overall survival time (OST) and recurrence/persistence free time (RPFT) by gene methylation
| Multivariable cox model | Stratified cox proportional hazards model | |||||
|---|---|---|---|---|---|---|
| Gene methylationa | Nb | Multivariable HR (95 % CI)c,d | Stratified model among HPV + c,e | Stratified model among HPV-c,e | p-valuef | |
| OST | CCNA1 | 341 | 1.13 (0.81, 1.59) | 0.62 (0.25, 1.52) | 1.25 (0.86, 1.81) | 0.16 |
| NDN | 346 | 2.35 (1.40, 3.94) ** | 3.12 (0.95, 10.21) | 2.22 (1.25, 3.92)* | 0.61 | |
| CD1A | 342 | 1.31 (1.01, 1.71)* | 3.34 (1.88, 5.93)** | 1.13 (0.84, 1.51) | 0.001** | |
| DCC | 344 | 1.30 (0.95, 1.78) | 1.45 (0.59, 3.60) | 1.28 (0.91, 1.79) | 0.79 | |
| p16 | 343 | 1.11 (0.93, 1.32) | 0.76 (0.48, 1.19) | 1.17 (0.97, 1.42) | 0.08 | |
| GADD45 | 340 | 0.88 (0.66, 1.17) | 0.80 (0.43, 1.50) | 0.91 (0.66, 1.25) | 0.73 | |
| RPFT | CCNA1 | 334 | 0.81 (0.57, 1.14) | 0.31 (0.13, 0.74)* | 0.96 (0.66, 1.42) | 0.02* |
| NDN | 339 | 1.86 (1.12, 3.07)* | 2.08 (0.70, 6.19) | 1.77 (1.00, 3.13) | 0.79 | |
| CD1A | 335 | 1.24 (0.95, 1.62) | 2.06 (1.21, 3.49)* | 1.07 (0.79, 1.46) | 0.04* | |
| DCC | 337 | 1.32 (0.96, 1.83) | 0.97 (0.40, 2.34) | 1.37 (0.97, 1.94) | 0.47 | |
| p16 | 336 | 1.00 (0.84, 1.19) | 0.91 (0.57, 1.46) | 1.00 (0.84, 1.20) | 0.72 | |
| GADD45 | 333 | 1.12 (0.87, 1.46) | 0.84 (0.49, 1.42) | 1.23 (0.91, 1.66) | 0.22 | |
Each row represents the hazard ratios in the multivariable or stratified Cox Proportional Hazards model for each gene. The top panel lists all overall survival time models and the bottom panel lists all recurrence/persistence-free survival time models. aAll genes log-transformed to better fit the linear functional relationship between predictor and outcome bn number of subjects in models cAll methylation measurements standardized to interquartile ranges. HRs are interpreted as comparison between those with methylation in the 25th percentile compared to those with methylation in the 75th percentile dMultivariable HR calculated from a multivariable Cox Proportional Hazards model after controlling for: age, HPV status, disease site, stage, and comorbidity score in the OST model and age, HPV status, disease site and stage in the RPFT model. eMultivariable HR (95 % CI) calculated from a stratified multivariable Cox Proportional Hazards model to allow for differing baseline hazard functions for HPV+ and HPV- groups. These models include an interaction of HPV status and gene methylation. Hazards listed for each HPV group in the stratified models calculated from this interaction term. Stratified OST models control for: age, disease site, stage, and comorbidity score and stratified RPFT models control for: age, disease site and stage. fp-value for interaction term. *p-value < 0.05; **significance at the Bonferroni-adjusted p-value < 0.004