Combined impact of extracapsular extension (ECE) in neck nodes and HPV-DNA detection on survival among p16+ oropharyngeal squamous cell carcinoma (OPSCC) patients

Background Extracapsular extension (ECE) in neck nodes (N+) and p16-status are newly introduced as prognostic factors in TNM 8th edition (2017) in oropharyngeal squamous cell carcinoma (OPSCC). However, ECE and HPV-DNA-status are still not taken into consideration in TNM staging of p16+ OPSCC.

Methods A cohort of 92 surgical resected p16+ N+ OPSCC patients with full pathologic information on ECE was available for confirmatory proof of p16-status in additional samples on tissue micro-arrays (TMA) and HPV-DNA detection. Outcome related to ECE and HPV-DNA status was analyzed utilizing Kaplan-Meier plots and log-rank tests for local control (LC), nodal control (NC), distant control (DC), progression-free survival (PFS), disease-free survival (DFS), event-free survival (EFS), tumor-specific survival (TSS) and overall survival (OS).

Results 62/92 (67 %) p16+ OPSCC were ECE+ and 30/92 (33 %) ECE-. 66/92 p16+ OPSCC (71.7 %; A) were HPV16DNA+ and >70 % cells stained p16+ in both samples. 26/92 (28.3 %; B) were HPV16DNA- or had <70 % p16+ in one IHC. Group A shows superior mean survival (months) in NC (59.0 vs. 52.6; p = 0.030), PFS (46.6 vs. 35.1; p = 0.046), DC (55.3 vs. 41.3; p = 0.003) and DFS (46.2 vs. 34.2; p = 0.044) compared to B. In A, ECE+ demonstrated impaired OS (p = 0.013), TSS (p = 0.026) and EFS (p = 0.025). Mean OS (months) were inferior in HPV16DNA-ECE+ (36.9; F) and HPV16DNA+ECE+ (45.1; D) OPSCC, compared to HPV16DNA+ECE- (60.0; C) and HPV16DNA-ECE- (52.1; D; p = 0.025). In DFS (p = 0.022), PFS (p = 0.022) and EFS (p = 0.001), group C had best and group F worst outcome.

Conclusion ECE+ and HPV16-DNA proof are independent prognostic factors for p16+ OPSCC affecting outcome. Considering both factors improves staging of p16+ OPSCC.

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Publication History

Article published online:
10 June 2020