Investigating Rates and Outcomes of Secondary HPV-Positive Oropharyngeal Cancers

Introduction: The prevalence, outcome, and treatment implications of patients with multiple human papillomavirus (HPV) positive oropharyngeal squamous cell cancers (OPSCC) are poorly understood. Contralateral tonsillectomy and/or biopsy of other oropharyngeal sites remain controversial.

Methods: We conducted a retrospective case series of all consecutive patients with p16 (a prognostic marker for OPSCC and surrogate marker of high-risk HPV) positive OPSCC reviewed by our pathology team between 2012 (when p16 testing started being routinely used at our institution) and 2022. Operative and pathology reports were reviewed to identify meta– or synchronous p16+ disease—cancers excised at a different or the same time; but, in an anatomically distinct location. Patient characteristics were compared by multivariable testing and outcomes by log-rank testing.

Results: One-hundred ninety-seven patients were diagnosed with a p16+ HNSCC. Median follow-up was 41.5 months (interquartile range [IQR] 19.9–64.0 months). Patients were largely male (88.3%), non-smoking (54.8%), and, on average, 60.6 ± 1.5 years old. Primary sites of disease mainly included the tonsil (48.2%), base of tongue (37.6%), and glossotonsillar sulcus (7.1%). Eight patients (4.1%) had a secondary p16+ HNSCC, 5 of which were synchronous and 3 of which were metasynchronous. Sites of secondary malignancies included the contralateral tonsil (n=3), base of tongue (n=3), nasopharynx (n=1), and soft palate (n=1). There were no differences in between patients with/out secondary malignancies in terms of demographics, clinical histories, tumor staging, and outcomes.

Conclusions: Thorough interrogation of the entirety of Waldeyer’s ring (including the soft palate and tubal tonsils) should be performed as part of the workup and during treatment for HPV positive OPSCC. Rates of secondary malignancies are not negligible; however, careful consideration should be given to contralateral tonsillectomy and/or biopsy of other subsites at the time of surgery given lack of difference in outcomes.