Clinical and prognostic differences in oropharyngeal squamous cell carcinoma in USA and Denmark, two HPV high-prevalence areas

Background Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. Methods OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n=2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). Results There were significantly more HPV-positive (88.2% vs. 63.1%), males (89.4% vs. 74.1%), never-smokers (52.1% vs. 23.7%), lower UICC8-stage (I/II: 79.3% vs. 68%), and fewer patients treated with radiotherapy (RT) alone (14.8% vs. 30.3%) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p=0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p=0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p=0.004, RFI HR 2.80, p=0.002). Conclusions We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.