Salivary High-Risk Human Papillomavirus DNA as a Biomarker for Human Papillomavirus–Driven Head and Neck Cancers

High-risk human papillomavirus (HR-HPV) infection is one of the major risk factors for head and neck cancers (HNC). Despite the rising incidence, biomarkers for detection, prognostication and disease monitoring of HPV-driven HNC (HPV-HNC) are lacking. To evaluate the capacity of salivary HR-HPV DNA as a biomarker for HPV-HNC, salivary HR-HPV status of 491 primary HNC patients and 10 recurrent HNC patients was investigated at diagnosis using qPCR and MassARRAY. Tumor Cyclin-dependent kinase inhibitor 2A (p16) expression was determined by immunohistochemistry. Oropharyngeal cancer (OPC) patients (N=215) were followed-up up to 5 years and survival characteristics were evaluated in terms of event-free survival (EFS) and cause-specific survival (CSS). In the primary HNC patient cohort, 43.2% were positive for salivary HR-HPV DNA and the vast majority of them had OPC. Salivary HR-HPV DNA could be detected in 81.4% of tumor p16 positive OPC patients at diagnosis. Furthermore, salivary HR-HPV positive OPC patients had a favorable prognosis over salivary HR-HPV negative patients (EFS; HR: 0.42; 95%CI, 0.21-0.81, p=0.010, CSS; HR: 0.39; 95%CI, 0.18-0.86, p=0.019). In the recurrent HNC cohort, salivary HR-HPV DNA was detected in 83.3% (5/6) of the patients who previously had tumor p16 positive HNC. Findings of this study indicate that this liquid biopsy-based, non-invasive biomarker can play an essential role in the detection and management of HPV-HNC.