Impact of Smoking on Treatment Outcomes in Patients With Human Papillomavirus-Related Oropharyngeal Cancer.

Kwan, Michelle M; Bazzi, Latifa A; Sun, Zequn; Rand, Dayton; Park, Asher; Asthana, Shravan; Larson, Alexis; Yadav, Poonam et al. · Head Neck · 2026

retrospective_cohort · Level III

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Abstract

Patients with HPV+ oropharyngeal cancer (OPC) have worse outcomes with longer smoking history (≥ 10 pack-years). This has been confirmed in trials of primary radiotherapy but not surgery, suggesting differential smoking impact by treatment received. We assessed smoking-related outcomes at a single institution. Kaplan-Meier and Cox proportional hazards regression compared < 10 versus ≥ 10 pack-years by treatment received for progression-free survival (PFS) and overall survival (OS). Smoking was associated with worse PFS in both primary (chemo)radiation (HR = 1.73 [1.12-2.69], p = 0.01) and primary surgery cohorts (HR = 1.77 [1.02-3.07], p = 0.04). In surgery patients, this association was attenuated after adjusting for socioeconomic indicators (HR = 1.69 [0.97-2.93], p = 0.06). On recursive partitioning analysis, ≥ 25 pack-years was associated with worse PFS and OS overall and among radiotherapy patients. Smoking impacts outcomes in HPV + OPC regardless of treatment modality. Treatment-specific differences in prior randomized studies may reflect underlying differences in patient characteristics. ≥ 25 pack-years was associated with worse outcomes.