AbstractBackgroundWe analyzed the difference in treatment results according to safety margin range and studied the role of adjuvant therapy in patients with human papillomavirus‐positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC).Materials and methodsA total of 279 patients with HPV+ OPSCC were included in this study.ResultsSurgical margin and T classification were significant prognostic factors related to death. The difference in locoregional recurrence was analyzed by dividing the safety margin into groups of <1, 1–5, and >5 mm. There was no significant difference in local‐regional recurrence for T1–T2 lesions between the three groups. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.ConclusionsIn T1–T2 lesions without other risk factors, even with a safety margin ≥1 mm, adjuvant therapy can potentially be omitted. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.