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Objective To describe the clinical and biologic characteristics and outcomes of young and middle-aged (YMA; <65 years) patients according to the presence or absence of traditional risk factors for laryngeal cancer. Study Design Retrospective cohort analysis. Setting Single-institution academic medical center. Methods Patients without a history of clinically significant tobacco use or heavy alcohol use were defined as “nontraditional”: ≤5 pack-years, ≤5 years smoked, ≤14 alcoholic drinks per week, and ≥15-year interval from last tobacco abuse use to diagnosis. Remaining patients were categorized as “traditional.” Select tumor samples were evaluated for bacterial and viral DNA by multiplex polymerase chain reaction. Results Seventy-eight YMA patients with primary laryngeal squamous cell carcinoma were identified, 23% (n = 18) of whom were nontraditional. Nontraditional patients were younger than traditional patients (median age, 51 vs 59 years; P < .001). Twenty-eight tumors were prospectively tested for human papillomavirus (HPV), and nontraditional patients were more likely to exhibit high-risk HPV (57% vs 5%, P < .01). Among 17 select tumors (nontraditional, n = 8; traditional, n = 9), 35% exhibited HPV16 (nontraditional, 63%; traditional, 11%; P = .05). Other viruses were identified but did not differ according to risk status: herpesviruses (40%) and Merkel cell polyomavirus (7%). Chlamydia, β-HPV, and γ-HPV DNA was not detected in any samples. Median length of follow-up was 42 months. On adjusted analyses, nontraditional patients exhibited nonsignificantly improved overall survival (hazard ratio, 0.24 [95% CI, 0.03-1.82]; P = .17) and disease-free survival (hazard ratio, 0.34 [95% CI, 0.10-1.23]; P = .08) as compared with traditional patients. Conclusion Almost one-quarter of YMA patients lacked characteristic risk factors for laryngeal squamous cell carcinoma, and their tumors exhibited a higher prevalence of high-risk HPV. The significance of HPV16 and other tumor viruses with outcomes in nontraditional patients should be evaluated further.

Background: The relative incidence of laryngeal cancer is rising in young patients, yet their characteristics, risk factors, and outcomes relative to older patients are poorly understood. Methods: Retrospective cohort analysis of the National Cancer Database from 2006 to 2015.Results: Among 25 029 total patients, 923 (3.7%) were young (<45 years old) and 3266 underwent tumor HPV testing. Compared to older patients, a greater proportion of young patients were female (30.3%, 23.3%; p < 0.001) and seen with high-risk HPV-positive tumors (29.9%, 12.4%; p < 0.001). In subset analyses of young patients, females with higher income (≥$38 000) exhibited a decreased risk of overall mortality compared to all other sex-income subcategories (adjusted hazard ratio [aHR]: 0.43, 95% confidence interval [CI]: 0.25-0.72). In subset analyses of patients of all ages with known tumor HPV status, patients with high-risk HPV-positive tumors exhibited a reduced risk of allcause mortality (aHR: 0.74, 95%CI: 0.60-0.92, p = 0.007). Conclusion:The interdependent associations between age, sex, tumor HPV status, and income on laryngeal cancer outcomes warrant further investigation.

Background: The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomaviruspositive (HPV+) oropharyngeal cancer (OPC) is debated.Methods: National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery.Results: Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p = 0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref; adjuvant radiation therapy [RT]: aHR: 0.81; 95% CI: 0.36-1.85; p = 0.62; adjuvant CRT: aHR: 0.66; 95% CI: 0.34-1.32; p = 0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p = 0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT. Conclusion:Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease. K E Y W O R D S extracapsular extension, human papillomavirus, oropharyngeal cancer, survival, treatment paradigm 1 | INTRODUCTION Despite the recent proliferation of de-escalation trials for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC), the results of many of these studies have not yet been comprehensively disseminated. Hence, among patients managed with primary surgery, the significance of extracapsular extension