Background: The interplay among prognosticators in OPC patients (pts) may be influenced by sociodemographic, geographic, epidemiologic and genetic features. We aimed to validate an existing prognostic nomogram (PN) (Fakhry et al 2017) in a large, independent, geographically homogeneous pt cohort. Methods: We retrospectively collected data on consecutive OPC pts treated with definitive IMRT (66-72 Gy) ± systemic therapy (ST) in 14 South-European Centres from 2007 to 2019. We analysed the role of the nomogram prognostic factors (PF) (T and N stage, age, p16 status, smoking, performance status, weight loss, anemia, education, and marital status) with respect to overall survival (OS) and progression-free survival (PFS), and we also evaluated alcohol abuse, comorbidities according to ACE-27 and the presence of a caregiver as added PF. The PN was evaluated in terms of discrimination performance (Harrel C-index) and calibration (ratio O/E and calibration line). Model was recalibrated evaluated via optimism adjusted C-index. Results: We considered 786 pts, with a median follow-up of 63 months (0-189). The table reports pts characteristics. The PN showed a good discrimination for OS and PFS both at 2- and 5-years, not dissimilar from original external validation, with a C-index of 0.75 (CI 95% 0.70-0.79,) and 0.68 (0.64-0.72), respectively. Adding alcohol abuse, comorbidities and caregiver presence did not change the PN. Regarding OS, the model estimated risk was slightly higher than the observed, with an O/E ratio of 0.73 (CI 95% 0.57-0.93) and 0.60 (0.49-0.74) at 2- and 5- years and calibration slope of 1.07 (0.83-1.31). For PFS, the O/E ratio was 0.48 (0.40-0.58) at 2 years and 0.50 (0.42-0.58) at 5 years, and a calibration slope of 0.89 (0.66-1.12). Both for OS and PFS rescaling of baseline hazard and model coefficients resulted in a better calibrated model. Model was validated also after missing data imputation, via MCE (m=5) showing consistent estimates. Conclusions: We validated the prognostic nomogram developed by Fakhry et al. in a large independent European cohort, demonstrating its applicability. These real-life data may represent the benchmark for the design of new prospective clinical trials.