Table 3.

Multivariate analysis of OS and PFS for OPSCC patients collected between 1990 and 2008 in Heidelberg, Germany

ParameterHR (95% CI)P valueHR (95% CI)P value
Demographic, clinical, and behavioral factors
 Age (10 y)1.01 (0.82–1.26)0.91.02 (0.84–1.24)0.8
 Gender (female vs. male)1.09 (0.67–1.79)0.70.94 (0.60–1.46)0.8
 Clinical stage (IV vs. I–III)2.10 (1.25–3.54)0.0051.45 (0.94–2.24)0.09
 Therapy status (Radiation/chemotherapy vs. surgery)1.95 (1.26–3.03)0.0031.71 (1.13–2.59)0.01
  Current vs. never2.13 (0.84–5.38)0.12.56 (1.09–6.00)0.03
  Former vs. never1.24 (0.39–3.92)0.71.39 (0.50–3.88)0.5
  Current vs. never1.27 (0.50–3.22)0.61.12 (0.48–2.63)0.8
  Former vs. never1.41 (0.49–4.06)0.51.30 (0.50–3.38)0.6
Single HPV markersn
 HPV (reference)991.001.00
 HPV+970.67 (0.44–1.03)0.070.77 (0.53–1.12)0.2
 HPV (reference)991.001.00
 HPVlow640.82 (0.53–1.26)0.40.89 (0.60–1.31)0.5
 HPVhigh330.32 (0.14–0.73)0.0070.45 (0.23–0.90)0.02
 HPV (reference)991.001.00
 RNA480.91 (0.56–1.46)0.70.92 (0.60–1.43)0.7
 RNA+480.44 (0.24–0.80)0.0080.61 (0.37–1.02)0.06
 HPV (reference)991.001.00
 RNA plus CxCaRNA560.95 (0.61–1.49)0.80.94 (0.62–1.42)0.8
 CxCaRNA+400.28 (0.13–0.61)0.0010.50 (0.27–0.92)0.02
HPV marker combinations
 HPV (reference)991.001.00
 HPVtransf540.96 (0.62–1.51)0.90.96 (0.63–1.45)0.8
 HPVtransf+420.30 (0.14–0.62)0.0010.50 (0.28–0.90)0.02
p16INK4a Immunohistochemistry
 p16-low (reference)1231.001.00
 p16-high540.90 (0.55–1.49)0.71.07 (0.69–1.66)0.8
p16INK4a HPV DNA combination
 HPV (reference)991.001.00
 p16-low+HPV+500.70 (0.43–1.13)0.10.74 (0.48–1.14)0.2
 p16-high+HPV+420.55 (0.29–1.08)0.080.83 (0.47–1.44)0.5

NOTE: HR for age, gender, clinical stage, therapy status, and alcohol and tobacco consumption were calculated using a Cox model including only these factors. HR for single HPV markers were computed using 4 different models: (i) DNA model (HPV+, HPV16 DNA–positive OPSCC), (ii) viral load model (HPVlow, OPSCC with low viral load; HPVhigh, OPSCC with high viral load), (iii) RNA models (RNA, DNA-positive and RNA-negative OPSCC; RNA+, DNA-positive and RNA-positive OPSCC, or (iv) RNA pattern model (RNA plus CxCaRNA, DNA-positive and RNA-negative OPSCC plus DNA-positive and RNA-positive OPSCC without CxCa-like viral RNA patterns; CxCaRNA+, DNA-positive and RNA-positive with CxCa-like viral RNA patterns). HRs were also calculated for HPV marker combinations: HPVtransf, OPSCC with low viral load, but without CxCa-like viral RNA patterns; HPVtransf+, OPSCC with high viral load and/or CxCa-like viral RNA patterns. HPV group (HPV16 DNA-negative OPSCC) resulting from BSGP5+/6+-PCR/MPG analysis was reference category for all models. p16-low or p16-high, OPSCC with low or high p16INK4a expression level analyzed by IHC. Models were adjusted by age, gender, clinical stage, therapy status, and alcohol/tobacco consumption. Missing values in covariates were imputed. Statistically significant values are in bold. P values were calculated for each marker model separately.