AbstractBackgroundThe role of induction chemotherapy (IC) in oropharyngeal squamous cell carcinoma (OPSCC) remains controversial. Its interpretation can be confounded by heterogeneity in chemosensitivity and human papillomavirus (HPV) status. This study aimed to investigate the prognostic impact of IC response in HPV‐positive and ‐negative OPSCC.MethodsPatients with OPSCC who underwent IC and concurrent chemoradiotherapy (CCRT) were retrospectively analyzed. Radiologic response to IC by ≥50% was defined as IC‐sensitive (IC‐s), while lesser response was deemed as IC‐resistant (IC‐r). Progression‐free survival (PFS) and overall survival (OS) were compared between subgroups.ResultsA total of 51 HPV‐positive and 57 HPV‐negative patients were included. IC‐s patients accounted for 55.6%, 62.7%, and 49.1% in the entire cohort, HPV‐positive, and HPV‐negative subgroup, respectively. Compared with IC‐r subgroup, IC‐s was associated with better clinical outcomes either in the entire cohort (3y‐PFS 91.7%vs.43.7%,P< 0.001; 3y‐OS 98.3% vs. 67.4%,P= 0.002), the HPV‐positive subgroup (3‐year PFS 94.7% vs. 47.9%,P< 0.001; 3‐year OS 100% vs. 73.5%, P = 0.055) or the HPV‐negative subgroup (3‐year PFS 88.2% vs. 40.9%,P= 0.001; 3‐year OS 96.4% vs. 63.1%,P= 0.026). Multivariate analysis demonstrated that response to IC represents an independent prognosticator for 3‐year PFS (HR, 0.088; 95% CI, 0.027–0.289;P< 0.001) and 3‐year OS (HR, 0.100; 95% CI, 0.021–0.477;P= 0.004).ConclusionsResponse to IC exerts a critical predictive effect on prognosis of both HPV‐positive and ‐negative OPSCC. Personalized treatment strategy based on IC response is worthy of further exploration in the future.