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

Eric Adjei Boakye, Paula Buchanan, Leslie Hinyard, Katie Stamatakis, Nosayaba Osazuwa-Peters, Matthew C. Simpson, Mario Schootman, Jay F. Piccirillo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish
Pages (from-to)1828-1835
Number of pages8
Issue number8
StatePublished - Aug 2019


  • Epidemiology
  • Head and neck squamous cell carcinoma
  • Surveillance
  • and End Results (SEER)
  • human papillomavirus
  • risk factor
  • second primary malignancy
  • survival


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