Extranodal extension is a strong prognosticator in HPV‐positive oropharyngeal squamous cell carcinoma

Abstract

Objective To comprehensively examine the prognostic significance of extranodal extension (ENE) in human papillomavirus–positive oropharyngeal squamous cell carcinoma (HPV‐positive OPSCC). Methods Retrospective cohort of cases diagnosed with HPV‐positive OPSCC from 2010 to 2015 in the National Cancer Database. Inclusion of all OPSCC HPV‐positive cases with appropriate International Classification of Diseases‐0‐3 codes that received surgery with a neck dissection. Univariate and multivariable analyses were conducted. Hazard ratios (HR) for the independent effects of ENE and N stage on overall survival were estimated by Cox proportional hazards regression. Results Cases that were ENE‐negative had the highest 5‐year survival (92.6%; 95% confidence interval [CI]: 90.5%–94.7%). ENE‐positive cases had the lowest 5‐year survival (84.0%; 95% CI: 80.7%−87.4%). After adjusting for confounding variables, ENE‐positivity was associated with almost twice the hazard of death (HR = 1.90; 95% CI: 1.35–2.67) compared to ENE‐negative cases. Nodal (N) category 1, ENE‐positive status was associated with an increased risk of death (HR = 1.88; 95% CI: 1.26–2.80) compared with N1, ENE‐negative status. Compared to N1/ENE‐negative cases, N2/ENE‐positive cases had the poorest survival (HR: 2.93; 95% CI: 1.94–4.43). Both microscopic and macroscopic ENE were associated with worse outcomes compared to node‐positive/ENE‐negative status. Conclusion The implementation of the American Joint Committee on Cancer 8th edition staging system provides a much‐improved framework to develop and discuss treatment plans for HPV‐positive OPSCC. We feel that careful consideration should be given to the importance of ENE in patients with HPV‐positive OPSCC. Level of Evidence 4 Laryngoscope, 130:939–945, 2020

Significance of Extranodal Extension in Surgically Treated HPV-Positive Oropharyngeal Carcinomas

“…For instance, Bauer et al in their 2019 study illustrated the importance of the extent of ENE in patients with OPSCC (5). Patients were classified into the categories ENE-negative, microscopic ENE, and macroscopic ENE, and patients with microscopic ENE showed significantly reduced survival compared to patients with negative ENE status (hazard ratio = HR = 1.52; 95% CI = 1.00-2.31; p = 0.048) (5). Patients with macroscopic ENE had the worst outcome (HR = 2.50; 95% CI = 1.39-4.51; p = 0.002) (5).…”

“…Patients were classified into the categories ENE-negative, microscopic ENE, and macroscopic ENE, and patients with microscopic ENE showed significantly reduced survival compared to patients with negative ENE status (hazard ratio = HR = 1.52; 95% CI = 1.00-2.31; p = 0.048) (5). Patients with macroscopic ENE had the worst outcome (HR = 2.50; 95% CI = 1.39-4.51; p = 0.002) (5). In addition to that, recent data even differentiate between the categories "no ENE, " "minimal ENE" (≤1 mm beyond the lymph node capsule"), and ">1 mm beyond the lymph node capsule" (6).…”

“…Bauer et al recently showed that ENE represents a significant prognostic parameter in respect of overall survival in HPV-mediated OPSCC (5). In their paper published in 2019, they analyzed the prognostic significance of ENE in a group of 4,153 patients with HPV-positive OPSCC from the NCDB who were treated surgically and by neck dissection (N0 = 531, ENE-positive: 1,429, ENE-negative: 2,193-surgery only: n = 923, surgery/radiation: n = 1,403, surgery/radiation/chemo: n = 1,827) (5).…”

Predictive value of computed tomography in identifying extranodal extension in human papillomavirus‐positive versus human papillomavirus‐negative head and neck cancer

“…Some studies found the presence of pENE not to be a prognostic factor while others showed that only grade 4 pENE, in the form of soft tissue metastasis, to impact survival. 7,9,10,[33][34][35] Although there was no systematic reporting of pENE grade that was meta-analyzable, Patel et al described the extent of pENE for matching rENE in HPV-positive HNSCC. This study defined macroscopic pENE as greater than 2 mm of extension beyond the capsule, and found that radiographic nodal size ≥3 cm had significant correlation with macroscopic pENE.…”

EPHB2 carried on small extracellular vesicles induces tumor angiogenesis via activation of ephrin reverse signaling

“…Head and neck squamous cell carcinoma (HNSCC) is an invasive cancer that originates in the oral cavity, larynx, and pharynx, in association with alcohol and tobacco use or exposure to human papillomavirus (1)(2)(3). While much of the morbidity of HNSCC is caused by local invasion into nerve and vascular tissues of the neck, mortality is driven primarily by metastasis to regional lymph nodes and distant organs (4)(5)(6)(7). A key event that facilitates this metastasis is tumor-associated lymph and blood vessel formation ( Figure 1A).…”