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Background: There is a paucity of data concerning molecular heterogeneity among glottic squamous cell carcinoma, and the clinical implications thereof., Methods: Data corresponding to glottic squamous cell carcinoma were derived from The Cancer Genome Atlas. The Onco-GPS computational methodology was levied to derive four patterns of transcriptional activity and three functional subtypes of glottic cancer., Results: Thirty glottic cancer samples stratified to three distinct oncogenic states (S0-S2) based on a Onco-GPS model containing four transcriptional components (F0-F3). Membership in S2 and association with transcriptional component F0 conveyed an invasive phenotype, with transcriptional activity strongly reflecting EMT programming (including TGF-B and NF-KB signaling). S2 membership also correlated with inferior disease-specific survival (HR 9.027, 95% CI 1.021-79.767), and higher incidences of extracapsular spread and perineural invasion., Conclusions: We present a functional taxonomy of glottic cancer, with subtypes demonstrating differential upregulation of canonical oncogenic networks and survival implications., (© 2023 Wiley Periodicals LLC.)

Objectives: To compare overall survival outcomes associated with transoral laser microsurgery (TLM) with neck dissection versus definitive radiotherapy in the management of T2N0 supraglottic squamous cell carcinoma., Methods: Data were extracted from the National Cancer Database concerning patients with cT2N0M0 supraglottic cancer treated with either TLM and neck dissection with minimum lymph node yield of 10 or definitive radiotherapy. Predictors of overall survival were assessed via Cox proportional hazards regression., Results: Seventy-six cT2N0 supraglottic squamous cell carcinoma patients who underwent TLM with neck dissection (+/- adjuvant therapy) versus 991 patients who underwent radiotherapy. TLM was associated with an overall survival benefit (OR = 0.574; 95% CI 0.383-0.860) compared with radiotherapy. There was no difference in survival between TLM patients receiving adjuvant treatment and those receiving definitive radiotherapy., Conclusions: An up-front, TLM-based surgical approach to cT2N0 supraglottic cancer may offer an overall survival benefit compared with definitive radiotherapy, and should receive more frequent consideration as a primary approach to this disease process., Level of Evidence: 3 Laryngoscope, 133:601-606, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To explore the survival implications of human papillomavirus (HPV) positivity and subtype in larynx cancer through a national cancer database. To investigate staging discrepancies in larynx cancer associated with HPV status., Study Design: Retrospective observational cohort study., Setting: National Cancer Database., Methods: Data were extracted concerning adults with known HPV status who were treated between 2010 and 2016 for laryngeal squamous cell carcinoma. Patients without known HPV subtype were excluded. Cox multivariable regression models were fit to evaluate the survival impact of HPV status, characterized as a binary variable (HPV+ vs HPV-) and by subtype. Two- and 5-year survival rates were calculated via the Kaplan-Meier method and compared by stage between the HPV+ and HPV- cohorts per the log-rank test., Results: Patients with HPV+ larynx cancer were younger (60.5 vs 64.3 years, P < .001), more likely to have private insurance (37.2% vs 31.2%, P < .001), more commonly White (84.6% vs 82.4%, P = .013), and more likely to present with nodal disease (42.6% vs 33.0%, P < .001). HPV positivity and HPV subtype 16 were associated with improved overall survival. One-stage discrepancies in 5-year survival were observed between the HPV+ and HPV- cohorts: stage II HPV+ (69.45%) vs stage I HPV- (65.77%); stage IV HPV+ (47.67%) vs stage III HPV- (46.80%)., Conclusions: HPV positivity and infection with HPV subtype 16 are correlated with improved overall survival in patients with laryngeal squamous cell carcinoma, manifesting with a 1-stage incremental survival advantage. Future prospective studies are indicated to corroborate the findings from this large-population database retrospective study.

Objectives/hypothesis: Determine the accuracy of bone marrow cytologic evaluations in detecting occult cancellous invasion by squamous cell carcinomas (SCCa) beyond the original margins of bone resection that would have gone undetected without the use of intraoperative bone-marrow margin analysis., Study Design: Retrospective single institution cohort study., Methods: Retrospective chart review of imaging, clinical, pathological, and follow-up data of 51 patients who underwent mandibular resections with intraoperative bone-marrow cytologic evaluation. The accuracy of bone marrow cytologic evaluations to predict final bone margins was calculated. Five-year survival rates were determined., Results: The accuracy of bone marrow cytologic evaluations in detecting occult cancellous invasion by SCCa beyond the original margins of bone resection was 100%. Twelve percent (6/51) were found to have positive bone margins on cytology and were re-resected to obtain clear margins. Patients with a prior history of radiation had a significantly higher incidence of initially positive bone-marrow margins (P = 0.03). The patients with initially positive bone-margins did not have a significantly different prognosis than the patients with initially negative bone-marrow margins., Conclusion: 1) The consistent use of intraoperative bone-marrow cytologic evaluation, when applicable, will improve the ability to obtain clear bone margins. 2) Patients with a history of prior radiation therapy have a significantly higher risk of having occult cancellous invasion of SCCa beyond the original margins of bone resection. 3) The prognosis of patients with initially positive bone-marrow margins is not significantly different than patients with initially negative bone-marrow margins., Level of Evidence: 4., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)