2784 - Outcomes of HPV-Positive Oropharyngeal Cancer in Smokers vs. Non-Smokers
Presenter(s)
M. Kwan1, L. Bazzi2, Z. Sun2, A. Park1, S. Asthana3, A. Larson4, P. Yadav4, B. B. Mittal5, A. S. Akthar4, J. Lorch6, S. Samant3, U. Patel3, M. L. Mierzwa7, L. J. Mady8, K. O. Stepan3, and L. A. Gharzai4; 1Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA, Chicago, IL, 2Robert H. Lurie Comprehensive Cancer Center, Division of Biostatistics, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 3Department of Otolaryngology - Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 4Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, 5Department of Radiation Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 6Department of Hematology and Oncology, Northwestern University, Chicago, IL, 7Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 8Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University, Baltimore, MD
Purpose/Objective(s): Prior research found that patients with human papillomavirus (HPV)+ oropharyngeal cancer (OPC) who are smokers (=10 pack-years) experience poorer outcomes compared to non-smokers. However, this data has been demonstrated primarily in patients treated with radiotherapy (RT) as their primary treatment. In ECOG-ACRIN 3311, a primary surgical trial, smoking status was not related to poorer outcomes. It is unclear if patient imbalance or socioeconomic drivers contribute to these findings, as patients undergoing RT are typically older, with worse disease and more comorbidities. We hypothesized that smoking serves as a proxy for socioeconomic status (SES) and aimed to investigate how oncologic outcomes are affected by smoking status and other SES indicators.
Materials/Methods: We performed a retrospective review of patients with HPV+ OPC between 2010 and 2024. Demographics, smoking status, pack-year history, cancer staging, and survival information were collected. Recurrence-free survival (RFS) of patients who had <10 pack-years vs. =10 pack-years was compared using Kaplan-Meier estimates and Cox proportional hazards regression, with pre-specified subgroups of primary RT vs. primary surgery.
Results: 409 patients who had HPV+, non-metastatic OPC were identified, with a median age of 61 years (IQR: 54-67). 364 (89%) were male, 45 (11%) were female, and 187 (45.4%) were former/current smokers with a median pack-year of 25 (IQR: 18-35). 186 (45%) received RT as primary treatment, and 223 (55%) received surgery as primary treatment. After a median follow-up of 4.79 years, there were 25 recurrences and 8 deaths in the surgery group, and 27 recurrences and 26 deaths in the RT group. Overall =10 pack-year history was found to be significant for RFS (p=0.043). However, on multivariate analysis after adjusting for stage , area deprivation index (ADI), race, gender, age, the =10 pack-year history was no longer significant (p=0.053). In treatment subgroups, =10 pack-year smoking history did not significantly impact RFS in the surgery subgroup (p=0.86). In the RT subgroup, =10 pack-year smoking history significantly worsened RFS (HR=1.86, 95% CI: 1.09-3.19, p=0.024). After adjusting for stage, age, gender, race, and ADI in the RT subgroup, the HR increased (HR=2.10, 95% CI: 1.20-3.67, p=0.01). HR for the surgery subgroup was unable to be assessed after adjusting for T staging due to limited numbers.
Conclusion: In this single institution retrospective study, we find that smoking status (defined as =10 pack-year history) is not significant for RFS after accounting for staging and indicators of SES. However, among patients who received RT as their primary treatment, smoking status significantly impacts RFS even when adjusting for staging and SES. These findings suggest in the context of typical worse disease and comorbidities in patients undergoing primary RT, smoking worsens RFS independently of other SES indicators in patients with HPV+ OPC.