Plasma Cell-Free Human Papillomavirus DNA and Oral Gargle HPV DNA in Patients with HPV-Related Oropharyngeal Cancer Treated with Radiotherapy

Dynamic biomarkers that guide de-escalation strategies in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) remain an unmet need. In this study, we evaluated the kinetics of plasma cell-free HPV (cfHPV) DNA and oral gargle HPV DNA during radiotherapy in patients with low-risk HPV-related OPSCC. Data were obtained from a trial evaluating an adaptive model optimizing radiation fractionation in patients with low-risk (T0-2N0-1M0) HPV-related OPSCC undergoing radiotherapy. The primary objective was to determine whether week 4 plasma cfHPV DNA or oral gargle HPV DNA clearance is associated with reduction of target tumor volume (TTV) at week 4. A total of 325 plasma and 334 oral gargle samples from 50 patients with available baseline samples were analyzed. Higher baseline plasma cfHPV DNA was associated with higher nodal staging (P = 0.002), whereas oral gargle HPV DNA was detected more frequently in the tonsil or soft palate than occult or base of tongue primary tumors (P = 0.039). Week 4 plasma but not oral gargle HPV DNA clearance was associated with higher reduction of TTV at week 4 (P = 0.0063). Whereas week 4 plasma and oral gargle HPV DNA clearance was not associated with progression-free survival, a lower baseline plasma cfHPV DNA was associated with superior progression-free survival (P = 0.027). Week 4 plasma cfHPV DNA clearance aligns with reduction in TTV, and future studies are warranted to determine the role of early plasma cfHPV DNA clearance in biomarker-adapted de-escalation strategies. SIGNIFICANCE: Our findings may inform appropriate patient selection for low-risk HPV-related OPSCC based on cfHPV DNA in future deintensification studies, aimed at preventing or minimizing treatment-related toxicities in patients who may have lower risk of recurrence.