The Interplay between Age and Viral Status in EBV-Related Nasopharyngeal and HPV-Related Oropharyngeal Carcinoma Patients

SIMPLE SUMMARY: We analyzed 324 patients affected by loco-regionally advanced virus- and non-virus-related head and neck cancers treated with curative intent. We aimed at assessing the interplay between age and viral status on outcome (disease-free- and overall survivals) in these patients. We found that old patients had more comorbidities, and received less intensive treatments when compared to younger subjects. OS and DFS were shorter in older patients. However, after adjusting the models for stage, smoking, comorbidities, treatment strategy and dose intensity, no significant differences in terms of survival were observed according to age. Therefore, factors such as comorbidities, treatment intensity and stage have a prognostic role with differential impact on both virus and non-virus related tumors. Age should be considered as the expression of an array of host- and tumor-related features rather than an independent prognostic factor. ABSTRACT: Background. The aim of this work was to analyze the interplay between age and viral status on the outcomes in loco-regionally advanced oropharyngeal and nasopharyngeal cancer patients treated with radiotherapy and different chemotherapy combinations. Methods. A retrospective (2006–2017) analysis was performed on non-metastatic loco-regionally advanced oropharyngeal (both HPV+ and HPV−) and EBV+ nasopharyngeal cancer patients (young: <65 years vs. elderly: ≥65 years) treated with radiotherapy with or without chemotherapy. The impact of age and viral status on overall (OS) and disease-free survival (DFS) were studied with multivariable models, which were adjusted for smoking, stage, comorbidities, chemotherapy dose intensity and treatment strategy. Results. We analyzed 324 patients (146 HPV+ oropharynx, 63 HPV−, 115 nasopharynx). Elderly patients had more comorbidities, and received less intensive treatments when compared to younger subjects. Although OS and DFS were shorter in older patients, after adjustment for stage, smoking, comorbidities, treatment strategy and dose intensity, no significant differences in terms of survival were observed according to age (65 vs. 50 years of age: HR 1.89, 95% CI 0.45–7.84 for HPV+ OPC; HR 0.91, 95% CI 0.29–2.89 for HPV− OPC; HR 1.99, 95% CI 0.9–4.39 for NPC; p = 0.395). Conclusions. Several potential age-related (comorbidities, treatment intensity) and disease-related (stage) confounding factors play a prognostic role with differential impacts on both virus and non-virus-related tumors. In HPV+ oropharyngeal cancer and in EBV+ nasopharyngeal cancer patients, age should be considered as the expression of an array of host- and tumor-related features rather than an independent prognostic factor.