Head and Neck Lymph Node Metastases From Cancer of Unknown Primary: Outcomes From p16-Guided Mucosal Radiotherapy.

BACKGROUND

The AJCC 8th edition distinguishes p16-positive oropharyngeal head and neck carcinoma of unknown primary (HNCUP) due to its superior prognosis. However, standardized radiation volume guidelines are lacking. This study evaluates the safety of p16-guided mucosal volume reduction.

METHODS

A retrospective review of 126 HNCUP patients (2009-2023) was conducted. p16-negative patients received comprehensive mucosal and laryngeal irradiation; p16-positive patients received risk-adapted, reduced-volume radiation limited to the ipsilateral naso- and oropharyngeal mucosa and elective nodal regions. Acute and late toxicities were reviewed.

RESULTS

The cohort included 97 p16-positive and 29 p16-negative patients (median follow-up 38 months). Five-year overall survival was 90.0% versus 69.2% for p16-positive and p16-negative patients. All mucosal emergences and neck recurrences occurred within the radiation fields. Acute grade 3 toxicities were comparable between groups.

CONCLUSIONS

p16-guided mucosal volume reduction in HNCUP appears oncologically safe, without compromising disease control or survival, supporting radiotherapy volume de-intensification for p16-positive disease.