Impact of Human Papillomavirus-Negative Dominance in Oropharyngeal Cancer on Overall Survival: A Population-Based Analysis in Germany from 2018 to 2020

SIMPLE SUMMARY: The impact of the relation of human papillomavirus (HPV) infection and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. All patients with OPSCC (from 2018 to 2020) were included. OPSCC cases were 37.3% HPV-positive (+) (31.2% smokers; mean incidence: 2.91/100,000 population) and 57.8% HPV-negative (63.5% smokers; mean incidence: 4.50/100,000 population). HPV+ patients had significantly better OS than HPV-negative (−) patients. In multivariable analysis, HPV− patients had an increased 4.5-fold higher hazard of death, but the smoking status had no independent influence on risk of death. In binary logistic regression analysis, smokers showed a 4.5 increased odds ratio (OR) of being tested HPV− than for nonsmokers. HPV− smokers formed the majority in Thuringia. Optimizing OPSCC therapeutic strategies due to the dominance of HPV− is more important than discussing de-escalation strategies for HPV+ patients. ABSTRACT: The impact of the relation of human papillomavirus (HPV) and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. A total of 498 patients with OPSCC (76.9% men; mean age 62.5 years) from 2018 to 2020 were included. OPSCC cases were 37.3% HPV-positive (+) (31.2% smokers; mean incidence: 2.91/100,000 population) and 57.8% HPV-negative (63.5% smokers; mean incidence: 4.50/100,000 population). Median follow-up was 20 months. HPV+ patients had significantly better OS than HPV-negative (−) patients (HPV+: 2-year OS: 90.9%; HPV−: 2-year OS: 73.6%; p < 0.001). In multivariable analysis, HPV− patients (hazard ratio (HR) = 4.5; 95% confidence interval (CI): 2.4–8.6), patients with higher N classification (N2: HR = 3.3; 95% CI: 1.71–6.20; N3: HR = 3.6; 95% CI: 1.75–7.31) and with a higher cancer staging (III: HR = 5.7; 95% CI: 1.8–17.6; IV: HR = 19.3; 95% CI: 6.3–57.3) had an increased hazard of death. HPV− smokers formed the majority in Thuringia. Nicotine and alcohol habits had no impact on OS. Optimizing OPSCC therapeutic strategies due to the dominance of HPV− is more important than discussing de-escalation strategies for HPV+ patients.