Impact of Margins on Outcomes in HPV-Related Oropharyngeal Squamous Cell Carcinoma Treated With Surgery Only.

Objective: This study aims to evaluate the prognostic impact of surgical margin status in HPV-related oropharyngeal squamous cell carcinoma (OPSCCa) and examine the potential for revising surgical margin standards in HPV+ OPSCCa.

Study design: A retrospective cohort study.

Setting: This study was conducted across 4 tertiary oncology centers.

Methods: Charts of patients treated from 2010 to 2022 for HPV+ OPSCCa were reviewed. Eligible patients underwent surgery without adjuvant treatment for nonrecurrent, nonmetastatic HPV+ OPSCCa. Demographic, oncologic, treatment, and outcome data were collected. Patients with prior head and neck radiation or adjuvant therapy were excluded. Local control, locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) were compared based on surgical margins using the Kaplan-Meier method.

Results: Among 194 qualified cases, with a median follow-up of 41.63 months, most cases were pT1 (64.43%) or pT2 (34.54%). Recurrence occurred in 8.76% of patients, with most salvaged successfully. Analysis on univariable and multivariable modeling determined that margins less than 1 mm were considered close, and those ≥1 mm were considered clear. On multivariable modeling, surgical margins of <1 mm were associated with a hazard ratio of 3.69 (95% confidence interval [CI] 1.47-9.30) for LRR and 2.95 (95% CI 1.41-6.16) for DFS when compared to cases where margins were clear by 1 mm or greater.

Conclusion: In this multi-institutional cohort of early-stage HPV+ OPSCCa treated surgically without adjuvant therapy, margins <1 mm were associated with worse LRR and DFS. This suggests that traditional definitions of close margins in HPV-negative disease may not apply to HPV+ OPSCCa, warranting a revised definition for surgical margin standards.