HPV-enriched oropharyngeal head and neck cancer and inpatient outcomes: A national analysis of U.S. hospitalizations, 2016 to 2023.

e23173 Background: HPV-associated oropharyngeal cancer has favorable oncologic prognosis, but its inpatient risk profile is poorly defined. The HPV paradox hypothesis proposes lower inpatient mortality despite similar or higher acute complication burden. Methods: A retrospective, survey-weighted analysis of the National Inpatient Sample (NIS), 2016 to 2023, was performed including adults hospitalized with head and neck cancer (HNC) identified by ICD-10-CM codes C00 to C14 and C30 to C32 across any diagnosis field. Tumor site was assigned by first-hit anatomic code, and palliative encounters (Z51.5) were excluded. HPV-enriched status was defined by oropharyngeal site (C09 to C10). Outcomes included in-hospital mortality, mechanical ventilation, tracheostomy creation, shock, any airway intervention, length of stay (LOS), and hospitalization cost. Survey-weighted models used subpopulation methods and adjusted for demographics, year, payer, income quartile, admission characteristics, hospital factors, comorbidity burden when available, and site. In models including site, the oropharynx category was collinear with HPV-enriched status and served as the reference. Results: The cohort included 117,198 unweighted HNC hospitalizations (weighted national estimate 585,990). HPV-enriched oropharynx represented 16.85% (95% CI 16.61 to 17.10). HPV-enriched admissions involved younger patients (mean 63.18 vs 64.97 years) and fewer females (19.61% vs 29.57%). Crude inpatient mortality was similar between HPV-enriched and non enriched admissions (3.25% vs 3.29%). HPV-enriched admissions had lower rates of mechanical ventilation (5.84% vs 7.40%), tracheostomy (7.63% vs 16.89%), shorter LOS (6.19 vs 7.07 days), and lower mean costs ($23,855 vs $29,753). After adjustment, HPV-enriched status was not associated with inpatient mortality (OR 1.04, 95% CI 0.92 to 1.17) or shock (OR 1.02, 95% CI 0.88 to 1.19). HPV-enriched status was associated with lower odds of mechanical ventilation (OR 0.78, 95% CI 0.72 to 0.85), tracheostomy (OR 0.39, 95% CI 0.36 to 0.42), shorter LOS (−0.68 days, 95% CI −0.83 to −0.52), and lower costs (gamma-log coefficient −0.163, 95% CI −0.194 to −0.132), corresponding to 15% lower adjusted costs. Adjusted absolute risk differences were consistent. In stratified analyses restricted to patients requiring airway intervention, HPV-enriched status was associated with higher mortality (OR 1.45, 95% CI 1.19 to 1.77). A similar association was observed among patients with shock (OR 1.66, 95% CI 1.13 to 2.43). Conclusions: HPV-enriched oropharyngeal HNC admissions had lower airway intervention rates, shorter LOS, and lower costs without reduced inpatient mortality. Among patients with severe complications, HPV-enriched status was associated with higher mortality, identifying a high risk subgroup requiring targeted inpatient risk stratification.