Evaluation of Cell-Free HPV DNA in Patients With HPV-Associated Oropharyngeal Cancer Treated With Induction Chemotherapy and Response-Adaptive Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Patients with human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) have a favorable prognosis, yet current treatment regimens are associated with substantial acute and long-term toxicities. As such, there is a pressing need to establish a treatment de-escalation paradigm that optimizes the therapeutic to toxicity ratio. Cell-free HPV DNA (cfHPV-DNA) from plasma is emerging as an attractive noninvasive surrogate of disease burden in HPV+ OPC patients and represents a promising biomarker to guide treatment de-escalation strategies. Here we utilize a sensitive NGS-based liquid biopsy approach to evaluate dynamic changes in cfHPV-DNA levels in the context of risk and response-adaptive treatment for locoregional HPV+ OPC. <h3>Materials/Methods</h3> Longitudinal plasma samples were collected from patients with locoregional HPV+ OPC sequentially enrolled on a de-escalation protocol of induction chemotherapy followed by risk/response adaptive de-escalated locoregional therapy (NCT04572100). Neck CT or MRI was obtained for all patients at baseline and following induction chemotherapy. cfHPV-DNA was quantified in plasma samples collected at baseline and at the end of induction therapy using the SafeSEQ NGS-based assay. Changes in cfHPV-DNA levels were correlated with radiographic response to induction therapy per RECIST 1.1 criteria. <h3>Results</h3> At the time of analysis, both pre- (baseline) and post- induction therapy plasma samples were available from 9 patients. cfHPV-DNA was detected in baseline samples from all patients, revealing 100% clinical sensitivity in this cohort. Baseline cfHPV-DNA levels ranged from 11 to >13,000 HPV16 copies per 2 mL of plasma. All 9 patients demonstrated a decrease in cfHPV-DNA levels following induction therapy, with 8 of 9 patients (89%) showing full clearance of cfHPV-DNA. The observed cfHPV-DNA changes were 100% concordant with response to induction therapy determined radiographically, where all patients demonstrated tumor shrinkage. One patient with detectable cfHPV-DNA following induction underwent surgical resection, demonstrating a poor pathologic response with extensive residual tumor in tonsil and lymph node. <h3>Conclusion</h3> Using an NGS-based liquid biopsy approach in HPV+ OPC patients, we demonstrate that dynamic changes in cfHPV-DNA levels correlate with response to induction therapy. These data support the development of cfHPV-DNA assessment to guide personalized de-escalation in HPV+ OPC. Analyses are ongoing to further evaluate cfHPV-DNA as a reliable blood-based biomarker in the context of an adaptive de-intensification paradigm.