## 3 Results  
### Patient Population  
From December 2011 to December 2021, a total of 147 patients were initially included in the present study. Considering the potential role of the tumor subsite in relation to the HPV status [33], three patients with tumor subsites poorly represented, i.e., posterior wall (n = 2) and soft palate (n = 1), were excluded. The final patient cohort consisted of 144 patients, which was divided into a training set of 95 patients and a validation set of 49 patients, with a similar proportion of HPV-negative and HPV-positive patients (30%/70% versus 33%/67%, respectively) and T- and N-stage characteristics. The patient and tumor characteristics of both sets are reported in Tables 1 and 2, respectively. Tumor subsite, smoke, and alcohol intake were significantly different between HPV-positive and HPV-negative OPSCC (Table 1). A strong association between smoke and alcohol intake was found (\(p\) = 0.0005, from the Chi2 test).  
The ADC/D radiomic analysis of PT was not possible in 12 patients (9 in the training set and 3 in the validation set) because the primary tumor was considered too small or the image quality was not adequate for the feature extraction (motion artifacts and/or susceptibility-induced distortions were evident in proximity to the primary tumor, especially at the base of the tongue, but without affecting the LN analysis).  
In the training set, the PT and LN median volumes were 8.4 cm\({}^{3}\) (95% CI, 6.0-11.8 cm\({}^{3}\)) and 5.5 cm\({}^{3}\) (95% CI, 4.0-7.4 cm\({}^{3}\)), respectively; while in the validation set, they were 6.3 cm\({}^{3}\) (95% CI, 4.6-9.2 cm\({}^{3}\)) and 9.9 cm\({}^{3}\) (95% CI, 4.7-13.3 cm\({}^{3}\)), respectively. The differences in PT and LN volumes between the training and validation set were not significant (\(p\) = 0.23 and 0.25, respectively, from the Mann-Whitney test).  
\begin{table}
\begin{tabular}{l l l l l} \hline \hline
**Patient and Tumor Characteristics** & \multicolumn{2}{c}{**HPV-Negative (n = 28)**} & \multicolumn{2}{c}{**HPV-Positive (n = 67)**} & \multicolumn{1}{c}{\(p\)**-Value * **} \\ \hline  & & **n** & **n** & \\ \hline
**Gender** & Male & 26 (93\%) & 50 (75\%) & 0.051 \\  & Female & 2 (7\%) & 17 (25\%) & \\
**Age (mean \(\pm\) SD)** & & 66.4 \(\pm\) 9.3 & 64.4 \(\pm\) 9.3 & 0.334 \\ \hline
**Tumor subsite** & Tonsil & 10 (36\%) & 42 (63\%) & **0.023** \\  & Base of the & 18 (64\%) & 25 (37\%) & \\  & tongue & & & \\ \hline
**T-stage** & T1 & 4 (14.3\%) & 8 (11.9\%) & \\  & T2 & 5 (17.9\%) & 24 (35.8\%) & \\  & T3 & 4 (14.3\%) & 7 (10.4\%) & \\  & T4 & - & 28 (41.8\%) & \\  & T4a & 15 (53.6\%) & - & \\ \hline
**N-stage** & N0 & 5 (17.9\%) & 7 (10.4\%) & \\  & N1 & 4 (14.3\%) & 29 (43.3\%) & \\  & N2 & 5 (17.9\%) & 28 (41.8\%) & \\  & N3 & 14 (50\%) & 3 (4.5\%) & \\ \hline
**Smoke** & No & 7 (25\%) & 33 (49.3\%) & **0.009** \\  & Moderate & 2 (7.1\%) & 11 (16.4\%) & \\  & Heavy & 18 (64.3\%) & 23 (34.3\%( \\  & Unknown & 1 (3.6\%) & - & \\ \hline
**Alcohol intake** & No & 11 (39.3\%) & 43 (64.2\%) & **0.001** \\  & Moderate & 4 (14.3\%) & 18 (26.9\%) & \\  & Heavy & 11 (39.3\%) & 5 (7.4\%) & \\  & Unknown & 2 (7.1\%) & 1 (1.5\%) & \\ \hline \hline \end{tabular}
\end{table}
Table 1: Characteristics of patients and tumors in the training set.  
The patients belonging to the training set were all examined on the 1.5T system, while patients belonging to the validation set were in part examined on the 1.5T system (n = 30) and in part on the 3T system (n = 19), thus for this cohort it was applied the ComBat-based feature harmonization to reduce the scanner-related variability (see Supplementary Figure S1).