Long-Term Outcomes of Patients With HPV+ Unknown Primary Squamous Cell Carcinoma Treated With Transoral Surgery.

Barrett, Thomas F; Boukind, Adam; Enin, Kwasi; Pipkorn, Patrik; Zolkind, Paul; Harbison, Richard A; Rich, Jason T; Bockover, Spencer R et al. · Otolaryngol Head Neck Surg · 2025

retrospective_cohort · Level III

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Abstract

Transoral surgery with neck dissection and risk-directed adjuvant therapy for unknown primary HPV-associated squamous cell carcinoma is an effective strategy to identify the primary lesion, minimize radiation dose to the pharynx, and obviate the need for chemotherapy and/or radiation, but late survival outcomes and the development of second primary head and neck (HN) mucosal primaries have not been well described. Retrospective cohort study of HPV associated unknown primary oropharynx cancer treated with transoral surgery between 2001 and 2012 was performed. Academic medical center. Demographics, smoking history, staging, adjuvant therapy, disease status, and salvage therapy were reviewed. Kaplan-Meier estimates for disease-free, disease-specific, and overall survival were calculated. Second HN primaries were defined as mucosal lesions that were not HPV-associated, HPV-associated at a different subsite, or emerging 5 or more years after treatment. With a median follow-up for overall survival calculations of 13.0 years, overall survival, disease-specific, and disease-free survival estimates at 10 years were 87.7% (95% CI 79.9%-96.7%), 96.7% (92.2%-100%), and 91.7% (84.9%-99.0%), respectively. Of 15 deaths, only 2 were definitely related to the original cancer. Four patients had a recurrence within 5 years. Seven patients (10.9%) developed a second primary in the head and neck a mean 9.23 years after initial treatment, 3 of which were HPV+. Long-term overall, disease-specific, and disease-free survival for patients with HPV+ unknown primary carcinomas treated with transoral surgery, neck dissection, and risk-directed adjuvant therapy are excellent. A minority will develop second primaries HN cancers.

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