Predictors of Recurrence in Human Papillomavirus‐Associated Oropharyngeal Squamous Cell Carcinoma

OBJECTIVE: Despite improved survival for patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC), up to 30% of cancers recur. This study elucidates independent predictors of recurrence and survival in HPV+ OPSCC patients. STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary care center. METHODS: Patients diagnosed with HPV+OPSCC from 2014 to 2024 were included. Electronic health records were manually searched for demographic, oncologic, treatment, and outcomes data. The primary outcome was recurrence within 5-years of completion of primary treatment. The secondary outcome was 5-year survival. Kaplan-Meier and log-rank tests were performed for univariate analyses. Cox regression analysis identified independent predictors of recurrence and mortality. RESULTS: Of the 239 patients included, 61 (25.5%) experienced recurrence within 5 years after completion of definitive treatment. Of recurrent cases, over one-third involved distant metastases, predominantly to the lung, with a subset involving atypical sites such as bone, liver, and skull base. On multivariable Cox regression analysis, perineural invasion was independently associated with any recurrence (HR: 2.440, 95% CI: 1.330, 4.477) and distant metastatic recurrence (HR: 3.107, 95% CI: 1.097, 8.794). The overlapping oropharynx tumor subsite was significantly associated with mortality (HR: 2.102, 95% CI: 1.053, 4.198). CONCLUSION: Our results highlight distinct patterns of recurrence and survival which support the consideration of more individualized surveillance approaches, especially in HPV+ OPSCC patients with perineural invasion.