Table 3.
Cox univariate and multivariable analysis for overall and disease-free survival of patients with HPV-positive HNSCC
| Variable | Overall survival |
Disease-free survival |
||||||
|---|---|---|---|---|---|---|---|---|
| Univariate |
Multivariable |
Univariate |
Multivariable |
|||||
| Hazard ratio (95% CI) | p value | Hazard ratio (95% CI) | p value | Hazard ratio (95% CI) | p value | Hazard ratio (95% CI) | p value | |
| Age at diagnosis | 1.05 (1.01–1.09) | 0.009 | 1.03 (0.98–1.09) | 0.292 | 1.05 (1.01–1.08) | 0.005 | 0.99 (0.94–1.04) | 0.681 |
| Gender | ||||||||
| Female | 1.00 (ref) | NI | 1.00 (ref) | NI | ||||
| Male | 1.24 (0.43–3.60) | 0.695 | 1.53 (0.53–4.38) | 0.428 | ||||
| Smoking statusa | ||||||||
| < 10 pack-year | 1.00 (ref) | NI | 1.00 (ref) | NI | ||||
| ≥ 10 pack-year | 1.53 (0.68–3.42) | 0.301 | 1.59 (0.77–3.26) | 0.206 | ||||
| Alcohol (no. per week) | ||||||||
| No | 1.00 (ref) | NI | 1.00 (ref) | NI | ||||
| Yes | 1.73 (0.73–4.09) | 0.210 | 1.27 (0.56–2.87) | 0.563 | ||||
| Comorbidity | ||||||||
| No | 1.00 (ref) | NI | 1.00 (ref) | NI | ||||
| Yes | 1.34 (0.60–2.95) | 0.475 | 0.97 (0.45–2.10) | 0.936 | ||||
| ECOG PS | ||||||||
| 0 | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | ||||
| ≥ 1 | 3.10 (1.28–7.46) | 0.012 | 4.36 (1.33–14.25) | 0.015 | 2.90 (1.32–6.35) | 0.008 | 3.00 (1.07–8.43) | 0.037 |
| Primary tumor location | ||||||||
| Oropharynx | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | ||||
| Non-oropharynx | 2.98 (1.16–7.66) | 0.023 | 11.83 (2.57–54.43) | 0.002 | 2.98 (1.26–7.08) | 0.013 | 3.72 (1.02–13.54) | 0.046 |
| Tumor classification | ||||||||
| T0–T2 | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | ||||
| T3–T4 | 3.16 (1.44–6.95) | 0.004 | 2.11 (0.76–5.82) | 0.151 | 2.64 (1.26–5.53) | 0.010 | 1.58 (0.61–4.13) | 0.349 |
| TNM stage | ||||||||
| I–III | 1.00 (ref) | NI | 1.00 (ref) | NI | ||||
| IV | 0.97 (0.39–2.42) | 0.941 | 0.55 (0.26–1.16) | 0.115 | ||||
| Pathology | ||||||||
| Non-PD | 1.00 (ref) | NI | 1.00 (ref) | NI | ||||
| PD | 0.49 (0.15–1.62) | 0.241 | 0.61 (0.23–1.59) | 0.308 | ||||
| HPV genotype | ||||||||
| HPV genotype 16 positive | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | ||||
| HPV genotype 16 negative | 3.89 (1.77–8.52) | 0.001 | 0.96 (0.29–3.21) | 0.952 | 2.01 (0.98–4.12) | 0.057 | 0.52 (0.15–1.80) | 0.304 |
| HPV genotype 18 negative | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | ||||
| HPV genotype 18 positive | 5.06 (2.32–11.02) | < 0.001 | 10.87 (3.06–38.57) | < 0.001 | 3.26 (1.55–6.86) | 0.002 | 7.38 (2.02–26.92) | 0.002 |
| HR type | ||||||||
| HR type negative | 1.00 (ref) | 1.00 (ref) | NI | |||||
| HR type positive | 1.50 (0.46–4.92) | 0.502 | NI | 0.70 (0.25–2.00) | 0.511 | |||
| p16 status | ||||||||
| Positive | 1.00 (ref) | 1.00 (ref) | ||||||
| Negative | 5.55 (1.84–16.72) | 0.002 | NI | 1.92 (0.78–4.73) | 0.156 | NI | ||
| Unknown | 2.05 (0.70–6.03) | 0.192 | ||||||
Multivariable models for both overall survival and disease-free survival were analyzed with stratification of nodal classification (N0 vs. N1–N3), definite treatment (surgery vs. non-surgery), and type of HPV testing method (liquid microarray vs. DNA chip).
HPV, human papillomavirus; HNSCC, head and neck squamous cell carcinoma; CI, confidence interval; NI, not included; ECOG, Eastern Cooperative Oncology Group; PS, performance status; TNM, tumour, node, metastasis; PD, poorly differentiated; HR, high-risk.
a
Never smokers were included in ‘< 10 pack-year’ group.