BACKGROUND: Little data exists regarding the incidence of oropharyngeal and upper aerodigestive tract (UADT) second primary malignancies (SPM) among human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here we evaluate SPM rates among patients with HPV-related OPSCC. METHODS: A retrospective cohort study of 412 patients with HPV-related OPSCC who underwent transoral resection +/- adjuvant therapy at a single center between 1996 and 2018. RESULTS: Twenty patients (4.9%) developed SPM of the UADT, nine (2.2%) occurring in the oropharynx. Median time to diagnosis was 59.5 months (0-173 months). Risk of SPM was lower for patients receiving adjuvant radiation (aHR: 0.25, 95%CI: 0.08-0.78). There was no difference in overall or disease-free survival between those with and without SPM. CONCLUSION: The rate of SPM among patients with HPV-positive OPSCC is lower than reported rates among HPV-negative OPSCC. To date, this is the largest study evaluating SPM in patients with surgically treated HPV-positive OPSCC.
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