Abstract 3408: Longitudinal measurement of HPV copy number in cell free DNA predicts progression free survival in HPV positive oropharyngeal cancer

Abstract Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in global prevalence and is divided into two types dependent on association with human papillomavirus (HPV), with a more favorable prognosis in HPV+ve tumors. Assay of HPV copy number in plasma cell-free DNA (cfDNA) provides a minimally invasive method for detecting and monitoring tumor-derived HPV, with potential for enhancing clinical care. We have evaluated the utility of cfDNA droplet digital PCR (ddPCR) as a method for characterisation and longitudinal monitoring of patients with OPSCC in a prospectively recruited cohort of 104 OPSCC patients. ddPCR assay of cfDNA for five HPV types showed overall 95% concordance with p16 immunohistochemistry (IHC) and PCR analysis of solid tumor tissue. Longitudinal sampling in 48 HPV+ve patients, with median follow-up of 20 months, strongly predicted patient outcomes. Progression-free survival, stratified respectively by the presence or absence of detectable HPV cfDNA at a median of 13 weeks post-treatment, was 50% and 88% (p=0.001, hazard ratio 10.0 (95% CI 2.1-47.1)). In two patients, greater reliance on sequential HPV measurement would have avoided surgical intervention which ultimately did not confirm disease recurrence. The high concordance of pre-treatment plasma cfDNA-HPV analysis with p16 IHC and HPV-PCR of solid tissue, together with the predictive value and utility of sequentially measured post-treatment cfDNA-HPV copy number, provide a compelling case for the routine use of cfDNA-HPV ddPCR in management of OPSCC and for clinical trials to assess its impact on treatment outcomes. Citation Format: Martyna Joanna Adamowicz, Sophie J. Warlow, John P. Thomson, Lara M. Carey, Helen Thain, Robert Wescott, Kate Cuschieri, Lucy Q. Li, Brendan Conn, Ashley Hay, Iain J. Nixon, Timothy J. Aitman. Longitudinal measurement of HPV copy number in cell free DNA predicts progression free survival in HPV positive oropharyngeal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3408.