Background/Objectives: Human papillomavirus (HPV) is a well-established prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC); however, the short-term treatment response remains heterogeneous, particularly among HPV-positive patients. Given the high prevalence of malnutrition in head and neck cancer, this study examined whether baseline nutritional status, body composition and functional status were associated with early treatment response in OPSCC according to HPV status. Methods: A prospective observational multicenter cohort study of newly diagnosed OPSCC patients eligible for curative-intent treatment was conducted at three tertiary hospitals in Barcelona, Spain. Baseline assessments comprised anthropometry, computed tomography (CT)-based body composition at L3, functional performance tests, systemic inflammatory biomarkers and nutritional diagnosis by the Patient-Generated Subjective Global Assessment (PG-SGA). Early treatment response, assessed around 12 weeks post-therapy, was classified as complete remission (CR) or non-complete remission (NCR). Classification tree analyses were performed separately by HPV status. Results: Of 101 enrolled patients, 97 completed post-treatment assessment, of whom 51% were HPV-positive. Among HPV-positive patients, PG-SGA score was the main discriminating variable for early response within the classification tree model, with CR achieved in 74% of patients scoring <6 versus 33% of those scoring ≥6 (AUC 0.68, 95% CI 0.55–0.82). Conversely, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and age were the primary discriminating variables in HPV-negative patients (AUC 0.81, 95% CI 0.70–0.93). In both HPV subgroups, body composition and inflammatory markers were not retained in the analysis once nutritional and functional status were considered. Conclusions: PG-SGA-defined nutritional status was associated with early treatment response in HPV-positive patients, while functional status was the main variable retained in HPV-negative patients. These findings support the potential clinical value of standardized nutritional assessment in OPSCC and suggest that early identification of poor nutritional status or functional impairment may help refine supportive care planning at treatment initiation.

Background Oropharyngeal squamous cell carcinoma (OPSCC) of human papillomavirus (HPV)-positive status is increasing relative to HPV-negative disease. Nutritional features of OPSCC patients according to HPV status is unclear. Subjects/Methods: Canadian and Spanish patients with OPSCC were assessed for body mass index (BMI), weight loss grade (WLG), and computed tomography-defined skeletal muscle index (SMI). Chi-square, t-test, Mann-Whitney-U, Kruskal-Wallis tests were conducted to compare HPV positive and negative groups. Overall survival (OS) was assessed by univariable Kaplan-Meier and Cox proportional hazard methods. Results No differences in BMI, WLG, SMI and adipose tissue index between the 308 (Canada) and 134 (Spain) patients according to HPV status; hence cohorts were pooled (n = 442). HPV-positive patients (n = 317) were overweight/obese (72.8%), had WLG of 0/1 (59.6%) and high SMI (83.4%) while HPV-negative patients were normal/underweight (61.5%), had high WLG 3/4 (50.8%), and moderate/severe SMI depletion (46.9%)(p < 0.003). These overall differences notwithstanding, there was crossover i.e. 35% of HPV-positive patients had high WLG and/or moderate/severe muscle depletion and 29% of HPV-negative patients had minimal weight loss and high SMI. HPV-negative patients had a higher risk of mortality (HR 3.78, 95% CI 2.70 to 5.29, P < 0.001) and this difference was retained after multivariable adjustment for WLG, SMI, age, and disease stage (HR 3.19, 95% CI 2.12 to 4.79, P < 0.001). Conclusion Nutrition features of patients with OPSCC did not differ between Canada and Spain. Distinctive nutrition features exist in patients according to HPV status. The high heterogeneity of individual nutritional profiles invites an individualized approach to nutrition care.