Importance: The presence of extracapsular spread (ECS) of metastatic nodes is considered a poor prognosticator in Head and Neck Cancer, with postoperative chemoradiotherapy (CRT) often recommended over radiotherapy (RT) alone in such cases.  However, there is less clarity regarding the impact of ECS on Human Papilloma Virus (HPV) associated oropharynx squamous cell carcinoma (OPSCC) or carcinoma of unknown primary site (CUP). 

Objective: To investigate the prognostic impact of ECS according to HPV status in OPSCC and CUP.

Design: Retrospective cohort study between 1998 and 2015.  Median follow up was 31 months for all patients, and 50 months for surviving patients.

Setting: Academic Teaching Hospital

Participants: 83 patients with OPSCC (62) or CUP (21) undergoing neck dissection as part of initial treatment. 

Interventions: HPV status was determined by p16 immunohistochemistry.  Presence of ECS was extrapolated from pathology reports and extent of ECS determined by re-review of original pathology slides. 

Main outcome measures: Disease specific survival (DSS) and recurrence-free survival (RFS).

Results: There were 45 p16-positive and 38 p16-negative tumours.  51 patients had ECS, which was graded extensive in 43 cases.  Among the entire group, adverse predictors of RFS were p16-negative status (p=0.001) and ECS (p=0.02).  Adverse predictors of DSS were p16-negative status (p=0.001) and ECS (p=0.03).  Among p16-negative patients, ECS was significantly associated with worse RFS (p=0.006) and DSS (p=0.01).  In contrast, among p16-positive patients, ECS had no impact on RFS (p=0.93) or DSS (p=0.91).

Conclusions: Presence of ECS appears to have distinct impact on survival in OPSCC and CUP according to p16 status.  Our findings raise questions regarding necessity of postoperative CRT in p16-positive patients with ECS.