Assessment of HPV’s influence on survival in head and neck cancer: A pioneering large-scale cohort analysis and insights into HPV’s long-term prognostic impact stratified by smoking status.

Abstract

e18129 Background: Human papillomavirus (HPV) infection is a prominent risk factor for head and neck cancers (HNC) of the lip, oral cavity, and pharynx, often linked to improved prognosis. However, its long-term effects on survival and systemic comorbidities, particularly modulated by nicotine dependence, warrant further elucidation to inform precision oncology strategies. Methods: We investigated the long-term influence of HPV status on all-cause mortality and selected comorbidities in HNC patients, with stratification by nicotine dependence. This retrospective cohort study utilized deidentified electronic medical records from the TriNetX federated network. Adult patients (≥18 years) diagnosed with HNC were categorized into HPV-positive (HPV+) and HPV-negative (HPV-) cohorts, analyzed overall and within a nicotine-dependent subgroup. Propensity score matching (1:1) balanced cohorts on age, sex, race, ethnicity, body mass index, and ECOG performance status. Results: The overall matched cohort included 9,187 HPV- and 9,187 HPV+ patients. HPV+ status was associated with comparable mortality risk (risk difference (RD), -0.009 [95% CI, -0.021 to 0.003]) but enhanced survival (median survival, 6017 vs 5689 days; end-window probability, 46.67% vs 38.66%; log-rank P < .001; HR, 0.84 [CI, 0.79-0.89]). HPV+ patients showed increased volume depletion (RD, -0.025 [CI, -0.041 to -0.009]; HR, 0.81 [CI, 0.76-0.87]) and decreased lipid metabolism disorders (RD, 0.021 [CI, 0.006-0.036]), with favorable HRs for kidney disease (0.88 [CI, 0.80-0.95]) and ischemic heart disease (0.87 [CI, 0.79-0.94]). The nicotine-dependent matched cohort comprised 5,628 patients per group. Mortality was similar (RD, 0.008 [CI, -0.008 to 0.025]; HR, 0.95 [CI, 0.88-1.02]). HPV+ was linked to elevated malaise/fatigue risk (RD, -0.025 [95% CI, -0.044 to -0.006]; HR, 0.83 [CI, 0.76-0.91]), without significant differences in other comorbidities. Conclusions: HPV positivity in HNC is associated with superior long-term survival overall, but this benefit is attenuated in nicotine-dependent patients, underscoring the synergistic adverse effects of smoking and HPV. Elevated risks of electrolyte imbalances and fatigue in HPV+ subgroups highlight the need for tailored monitoring and supportive care to mitigate these complications.