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Background and Purpose: Standardized uptake value (SUV) and related parameters derived from 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) PET/CT prior to radiochemotherapy of head and neck cancer (HNC) were significantly associated with survival in a number of studies. The aim of this study was to validate these findings and to evaluate the prognostic role of PET parameters also including clinical factors and HPV status., Materials and Methods: We reviewed 166 HNC cases with a radiotherapy planning FDG PET/CT scan. All patients received radiotherapy, 68-70 Gy with or without concomitant cisplatin. Primary endpoint was disease-free survival (DFS). Twelve clinical factors, including HPV, performance status, stage and treatment parameters and ten PET/CT image parameters including gross tumor volume (GTV), metastatic lymph node volume, SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were collected. Univariate and multivariate Cox regression analyses were employed., Results: Of the 166 patients included, 48 had locoregional and 23 had metastatic recurrence. None of the FDG PET parameters were significant in the univariate analysis using DFS as endpoint. HPV status, ECOG status and GTV-U (primary tumor and lymph node volume from CT) were statistically significant (p < 0.01). Only in the subgroup of HPV-unrelated HNC (HPV negative oropharyngeal cancer [OPC] and non-OPC; n = 73), the multivariate model could be improved by including MTV (p < 0.001). DFS events were 29 (31%) in HPV-related and 53 (73%) in HPV-unrelated HNC., Conclusion: FDG PET parameters appear less important for overall prognostication of radiochemotherapy outcome for HNC. Still, the association between the FDG PET parameters and survival is strong for HNC not related to HPV. Tumor volume from CT is generally more closely related to outcome than parameters derived from FDG PET/CT., (Copyright © 2019 Elsevier B.V. All rights reserved.)