Extranodal extension following surgical resection of HPV-positive oropharyngeal cancer – is adjuvant radiotherapy alone sufficient?
Reviewed by Christopher Burgess

Human papillomavirus (HPV) is a known aetiological factor in oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive OPSCC is recognised to have a more favourable prognosis than HPV-negative disease. Treatment deintensification for HPV+ OPSCC has therefore been an area of research focus with a view to minimising treatment-related toxicity whilst maintaining optimal oncological outcomes. The presence of extranodal extension (ENE) after surgical resection has historically been considered to be an indication for adjuvant chemoradiation, but emerging data suggest that adjuvant radiation alone may be sufficient. This paper reviewed the outcomes of 63 patients treated with transoral robotic surgery and neck dissection for HPV+ OPSCC at a single institution in the USA with evidence of ENE affecting at least one cervical lymph node on histological analysis. Twenty patients received postoperative radiation (RT), with the remaining 43 receiving chemoradiation (CRT). The three-year overall survival for the entire cohort was 87%. No significant difference was observed between patients treated with RT vs. CRT in terms of overall survival (86% vs. 87%), loco-regional control (91% vs. 90%) and progression-free survival (83% vs. 85%). The incidence of grade 3+ toxicity was 25% in the RT cohort and 40% in the CRT cohort (p=0.01). Whilst this paper confirms that CRT is significantly more toxic than RT alone, the limitations of the study (small numbers and retrospective, non-randomised nature) mean that it cannot be confidently concluded from this data alone that RT is equivalent to CRT for the adjuvant treatment of ENE+ disease. Indeed the Kaplan-Meier curves included in the paper seem to show a worse five-year progression-free and overall survival rate (approximately 68% vs. 80%) amongst the RT cohort relative to the CRT cohort, although the significance of this difference is unclear. As is often the case, further research in the form of an adequately powered, prospective randomised controlled trial would be desirable to ascertain whether adjuvant RT alone provides truly equivalent oncological outcomes to adjuvant CRT in the context of pathological extranodal extension. 

Extra-capsular nodal extension after surgical resection for HPV-positive oropharyngeal cancer: adjuvant radiation versus chemoradiation.
Chen AM, Tjoa T, Armstrong WB.
AM J OTOLARYNGOL
2025;46(4):104639.