Synchronous, bilateral tonsillar carcinomas: Patient characteristics and human papillomavirus genotypes

Introduction: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing, but data on the incidence of synchronous, bilateral tonsillar squamous cell carcinomas (BiTSCCs) is sparse. In this study, we report the incidence and tumour characteristics of BiTSCCs in a population-based, consecutive cohort of OPSCCs.

Methods: We identified all patients diagnosed with tonsillar squamous cell carcinoma (TSCC) in eastern Denmark during a 15-year period to detect the incidence of synchronous BiTSCCs. The tumours were assessed for p16^Ink4a expression, the presence of HPV DNA and HPV genotypes. Furthermore, we systematically reviewed the literature examining BiTSCCs.

Results: Of the total of 1119 TSCCs diagnosed in eastern Denmark from 2000 to 2014, we identified 12 BiTSCCs, nine of which initially presented as a cancer of unknown primary (CUP) in the neck. Nine cases were bilaterally HPV16 positive (HPV16+), while two cases were HPV16+ in one tonsil and respectively, HPV33 and HPV35 positive in the contralateral tonsil. One case was bilaterally HPV-negative. We also identified an increase in the incidence of BiTSCCs after 2012 when histological examination of the entire tonsil tissue became routine, suggesting that BiTSCCs might be underdiagnosed. In the literature, we identified 15 studies from six countries, encompassing 25 cases in total.

Conclusions: BiTSCCs were primarily HPV16+ and were most often diagnosed as part of the diagnostic work-up for CUP. We found an incidence of 9% BiTSCCs in patients with TSCC after 2012 and we therefore recommend focusing on putative BiTSCC with total embedding and histological examination of tonsils harvested by bilateral tonsillectomies.