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

High-risk human papillomavirus (HR-HPV) infection is a major risk factor of head and neck cancers (HNCs). Despite the rising prevalence of HPV-driven HNC (HPV-HNC), biomarkers for detection, prognostication, and disease monitoring are lacking. To evaluate the capacity of salivary HR-HPV DNA as a biomarker of HPV-HNC, the salivary HR-HPV statuses of 491 and 10 patients with primary and recurrent HNC, respectively, were determined at diagnosis, using quantitative real-time PCR and MassARRAY. Tumor cyclindependent kinase inhibitor 2A (p16) expression was determined by IHC analysis. Patients with oropharyngeal cancer (OPC) (n=215) were followed up for <= 5 years. Survival characteristics were evaluated in terms of event-free and cause-specific survival. Of the primary-HNC cohort, 43.2% were positive for salivary HR-HPV DNA, with most having OPC. Salivary HR-HPV DNA was detected in 81.4% of tumor p16 epositive OPC patients at diagnosis. Prognosis in salivary HR-HPVepositive OPC patients was favorable compared with that in salivary HR-HPVenegative patients (event-free survival, hazard ratioZ0.42 [95% CI, 0.21-0.81, P = 0.010]; cause-specific survival, hazard ratio Z 0.39 [95% CI, 0.18-0.86, P Z 0.019]). In the recurrent-HNC cohort, salivary HR-HPV DNA was detected in 83.3% of those who previously had tumor p16-positive HNC. These findings indicate that this liquid biopsyebased, noninvasive biomarker can play an essential role in the detection and management of HPV-HNC.

Automated summary

Salivary HR-HPV DNA can serve as a biomarker for HPV-HNC, with better prognosis observed in OPC patients who test positive for this biomarker.