Prognostic significance of human papillomavirus 16 viral load level in patients with oropharyngeal cancer

Human papillomavirus (HPV) infection in patients with oropharyngeal squamous cell carcinoma (OPSCC) is a major determinant for better prognosis. However, there remain HPV‐positive patients who have poor outcomes. The stratification strategy for detecting high‐risk patients among those with HPV‐positive OPSCC has not been well delineated, especially for Asian patients. We undertook a retrospective cohort study on the survival rate of 89 Japanese patients diagnosed with primary OPSCC. The tumors were concurrently analyzed for the presence of HPV E6 DNA/mRNA, viral DNA load, p16 expression, viral physical status, and viral variant lineage. Human papillomavirus 16 viral DNA was found in 45 (51%) OPSCCs. Human papillomavirus 16 DNA‐positive OPSCCs with higher viral load (classified as HPV16 DNA‐medium/high OPSCCs) showed significantly favorable overall survival and progression‐free survival compared with HPV16 DNA‐positive OPSCCs with lower viral load (<10 copies/cell; HPV16 DNA‐low OPSCCs) and HPV16 DNA‐negative OPSCCs. E6 mRNA expression was observed in all HPV16 DNA‐medium/high OPSCCs but not in HPV16 DNA‐low OPSCCs. Notably, p16‐positive and HPV16 DNA‐negative/low OPSCCs showed significantly worse survival than p16‐positive and HPV16 DNA‐medium/high OPSCCs and resembled HPV‐unrelated OPSCCs with regard to survival and risk factor profile. Although not significant, a trend toward shorter survival was observed for HPV16‐integrated OPSCCs. Phylogenetic analysis revealed two major types of HPV16 variants termed Asian (A4) and European (A1/A2/A3) variants, but no difference in survival between these variants was observed. Altogether, these findings suggest that HPV viral load is a potentially informative factor for more accurate risk stratification of patients with OPSCC.