HPV ctDNA analysis in unresectable recurrent/metastatic oropharyngeal cancer.

Abstract

6554 Background: There is an increasing incidence of human papillomavirus associated (HPV+) oropharyngeal cancer (OPC). While HPV + portents improved prognosis, survival for patients with unresectable recurrent/metastatic (R/M) OPC remains poor. Extant data suggest that HPV ctDNA levels correlate with disease burden and treatment outcomes in patients with HPV + OPC in the primary setting but scant data exists in the metastatic setting. Objective: To develop a highly precise droplet digital (ddPCR) assay for quantification of plasma HPV ctDNA and to evaluate whether HPV ctDNA predicts treatment response in patients with HPV+ R/M OPC. Methods: Patients with HPV + R/M OPC starting systemic therapy were enrolled in a biorepository in which blood was collected prior to each cycle of therapy. PCR probes were created for the most common high-risk HPV subtypes, 16 and 18. HPV ctDNA was extracted from plasma and quantified with ddPCR. Percent change in HPV ctDNA was calculated after 1 and 2 cycles of treatment. Treatment response was assessed per standard of care or study protocol after 2-3 cycles of treatment. ROC curve analyses were performed. Results: A precise ddPCR assay was developed to identify plasma HPV ctDNA in 10 patients who underwent 16 distinct treatment courses. On ROC curve analysis, percent change in HPV ctDNA after 2 cycles of treatment was predictive of radiographic response (AUC 0.82, p = 0.03). The optimal cutoff point to optimize sensitive and specificity was identified as 30% change in HPV ctDNA (Table). Changes in HPV ctDNA after 1 cycle of treatment were also predictive of radiographic response (AUC 0.82, p = 0.05). Conclusions: Changes in HPV ctDNA may be predictive of treatment response in patients with R/M HPV + OPC. Furthermore, HPV ctDNA predicts response earlier than conventional imaging. While validation is needed, this assay shows promise in identifying poor responders who can be directed early towards clinical trials or alternative therapies. [Table: see text]