Risk and outcomes for second primary human papillomavirus–related and –unrelated head and neck malignancy

Objectives/Hypothesis To 1) examine the characteristics of patients who develop second primary malignancies (SPMs) from an index human papillomavirus (HPV)‐related head and neck squamous cell carcinoma (HNSCC) and HPV‐unrelated HNSCC and to 2) compare overall survival between those with HPV‐related and HPV‐unrelated index HNSCC among patients who develop SPM. Study Design Retrospective cohort analysis. Methods A retrospective study was conducted of 113,259 patients who were diagnosed with HNSCC from 2000 to 2014. SPM was defined as the first subsequent primary cancer occurring at least 2 months after index cancer diagnosis, and HPV‐relatedness was based on whether patients’ index HNSCC was potentially HPV‐related or HPV‐unrelated. Multivariable Fine and Gray (FG) competing‐risks regression models were used to estimate factors associated with risk of SPM by HPV‐relatedness. Among patients with SPM, an adjusted Cox proportional hazards (PH) regression model was used to assess the association between HPV‐relatedness and survival. Results Approximately 13,900 patients (12.3%) developed SPM. In the FG model, patients with HPV‐unrelated HNSCC had a 15% higher risk of developing SPM (adjusted hazard ratio: 1.15, 95% confidence interval: 1.10‐1.20) than those with potentially HPV‐related HNSCC, but the same characteristics were associated with SPM development. In the Cox PH model, patients with SPM whose index HNSCC was HPV‐unrelated had higher risk of death than those whose index HNSCC was potentially HPV‐related (adjusted hazard ratio: 1.06; 95% confidence interval: 1.02‐1.11). Conclusions Patients with HPV‐unrelated HNSCC have a higher risk of SPM development than do those with HPV‐related HNSCC. Effective secondary disease‐prevention strategies should be established to improve long‐term patient outcomes. Level of Evidence NA Laryngoscope, 129:1828–1835, 2019