High Level of Tregs Is a Positive Prognostic Marker in Patients with HPV-Positive Oral and Oropharyngeal Squamous Cell Carcinomas

Table 4

Factors with impact on patients’ survival (Cox regression analysis).

	Disease specific survival						Overall survival
	𝑃 value	HR	95% CI	Adjusted^a  𝑃 value	Adjusted HR	95% CI	𝑃 value	HR	95% CI	Adjusted^a  𝑃 value	Adjusted HR	95% CI
Gender
Female	Referent			Referent			Referent			Referent
Male	0.277	0.326	0.043–2.458	0.356	0.385	0.051–2.929	0.099	0.300	0.072–1.253	0.126	0.327	0.078–1.370
Age	0.035	0.972	0.920–1.026	NA			0.892	1.003	0.963–1.044	NA
Tobacco
Nonsmoker	Referent			Referent			Referent			Referent
Smoker	0.218	0.623	0.293–1.323	0.435	0.740	0.347–1.576	0.019	0.505	0.285–0.894	0.021	0.496	0.274–0.898
Alcohol
No	Referent			Referent			Referent			Referent
Yes	0.971	1.010	0.586–1.741	0.837	1.059	0.615–1.822	0.505	1.506	0.452–5.017	0.864	0.966	0.647–1.440
Tumor size
T1 + T2	Referent			Referent			Referent			Referent
T3 + T4	0.187	1.930	0.727–5.127	0.151	2.061	0.768–5.529	0.027	2.192	1.092–4.396	0.021	2.296	1.135–4.646
Nodal status
N0	Referent			Referent			Referent			Referent
N1–N3	0.091	3.565	0.959–1.033	0.020	6.035	1.334–27.305	0.188	1.700	0.771–3.747	0.064	2.228	0.995–5.194
Tumor grade
G1	Referent			Referent			Referent			Referent
G2 + G3	0.980	1.006	0.627–1.616	0.932	1.018	0.683–1.516	0.408	1.102	0.875–1.388	0.498	1.080	0.864–1.350
Tumor location
Oropharyngeal	Referent			Referent			Referent			Referent
Oral	0.631	1.363	0.386–4.814	0.993	1.006	0.277–3.653	0.812	0.881	0.309–2.51	0.508	0.697	0.239–2.029
Recurrence
No	Referent			Referent			Referent			Referent
Yes	0.0001	12.208	4.591–32.46	0.001	10.503	3.843–28.705	0.0001	6.936	3.372–14.268	0.0001	6.711	3.192–14.111
Tregs	0.054	0.917	0.840–1.001	0.061	0.920	0.843–1.004	0.459	0.984	0.943–1.027	0.525	0.986	0.956–1.029
Tregs
Low	Referent			Referent			Referent			Referent
High	0.098	0.428	0.157–1.171	0.085	0.413	0.151–1.129	0.097	0.563	0.286–1.109	0.103	0.568	0.269–1.123
CD4+	0.929	1.003	0.946–1.063	0.772	0.991	0.936–1.051	0.815	0.995	0.956–1.036	0.615	0.990	0.951–1.030
CD8+	0.260	1.032	0.956–1.105	1.091	1.027	0.972–1.085	0.199	1.026	0.987–1.066	0.236	10.023	0.985–1.063
CD4+CD8+sum	0.202	1.038	0.980–1.098	0.472	1.021	0.964–1.082	0.272	1.023	0.982–1.065	0.443	1.012	0.974–1.061
CD4+/CD8+	0.274	0.701	0.371–1.325	0.246	0.693	0.373–1.288	0.154	0.735	0.481–1.112	0.129	0.725	0.479–1.098
CD8+/Tregs	0.001	1.211	1.098–1.336	0.001	1.187	1.074–1.311	0.004	1.150	1.045–1.266	0.012	1.136	1.029–1.253
CD19	0.851	0.991	0.905–1.085	0.953	1.003	0.921–1.091	0.617	0.986	0.924–1.052	0.853	0.994	0.932–1.060
CD3–56+16+	0.020	0.885	0.798–0.981	0.062	0.905	0.815–1.005	0.295	0.986	0.911–1.029	0.409	0.974	0.915–1.037
HPV DNA
Negative	Referent						Referent
Positive	0.057	0.335	0.109–1.033	NA			0.125	0.582	0.292–1.162	NA

aadjusted for HPV and age, HR: hazard ratio 95% CI: confidence interval; 𝑃: probability.