Treatment outcomes for oropharyngeal cancer: Findings from an institutional study

Changshu Wang¹Jerome Costisella¹Benoit Emond-Guilbert²Isabelle Gauthier¹Pierre-Hugues Fortier¹Sameh Geha¹Ayman Oweida^1*Mathieu Belzile¹

• ¹Université de Sherbrooke, Sherbrooke, Canada
• ²Centre integre universitaire de sante et de services sociaux du Saguenay-Lac-Saint-Jean du Quebec, Chicoutimi, Canada

Introduction: Locally advanced oropharyngeal squamous cell carcinoma (OPSCC) represents a growing clinical challenge, primarily due to the increasing incidence of human papillomavirus (HPV)-associated disease. While treatment options include radiotherapy (RT) alone, RT with Cetuximab (RCX), or radiochemotherapy (RCT), the latter remains the standard of care. This retrospective study analyzed 359 patients with locally advanced OPSCC treated at CIUSSS de l’Estrie–CHUS since 2011 to evaluate how HPV status influences outcomes across different treatment regimens. Methods: Patients diagnosed between August 2011 and September 2022 with histologically confirmed OPSCC, known p16 status, and treated with curative intent were included. Treatment modalities consisted of RT alone, RCX, RCT with weekly or 3-weekly cisplatin, or RT combined with immunotherapy. Survival outcomes were compared based on HPV status and treatment type. Results: Of the 359 eligible patients, 86.4% were HPV-positive. Five-year overall survival (OS) and disease-free survival (DFS) were markedly higher in HPV-positive versus HPV-negative patients (OS: 80.4% vs. 35.4%, p<0.0001; DFS: 76.7% vs. 28.8%, p<0.0001). Among HPV-positive patients, RCT achieved superior outcomes compared to RT alone or RCX (5-year OS: 86.6% vs. 67.7% and 73.0%, p=0.0007; DFS: 83.0% vs. 62.1% and 63.8%, p=0.0011). Within RCT, 3-weekly cisplatin yielded better OS (92.6%) than weekly cisplatin (77.4%). In HPV-positive AJCC 8th edition N1 patients, those previously staged as N2b under AJCC 7th showed a trend toward inferior survival (74.5% vs. 86.2%, p=0.057). Multivariable analysis confirmed HPV positivity as an independent favorable prognostic factor (OS HR=0.31, 95% CI 0.19–0.51, p<0.0001; DFS HR=0.33, 95% CI 0.21–0.52, p<0.0001). RCT significantly improved OS (HR=0.55, 95% CI 0.33–0.92, p=0.024), while heavy smoking was associated with worse DFS (HR=1.9, 95% CI 1.1–3.27, p=0.022). Conclusion: This study demonstrates excellent outcomes for HPV-positive OPSCC, consistent with RTOG 0129 and 1016 trials. RCT, particularly with 3-weekly cisplatin, was associated with superior survival outcomes, with an absolute 15% difference in 5-year OS in HPV-positive patients compared with weekly cisplatin. RCT remains the standard of care, while HPV-negative disease continues to pose a major therapeutic challenge.