Individualized Treatment Responsiveness as Quantified by Dynamic Changes in Cell Free HPV DNA in Patients Receiving Induction Chemotherapy and Definitive Chemoradiation for HPV-Related Head and Neck Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Studies have shown that induction chemotherapy (IC) is a viable pathway to chemoradiation therapy (CRT) de-intensification in HPV-related head and neck cancer (HNC). However, reliance on imaging alone for eligibility may incorrectly exclude cases where radiographic response lags or otherwise confounds biological response. We report serial cell free HPV DNA (cfHPV DNA) dynamics as a quantitative measure of early treatment responsiveness for HPV-related HNC patients receiving IC followed by CRT. <h3>Materials/Methods</h3> Starting Sept 26, 2021, we enrolled patients with locally advanced, high-risk HPV positive HNC who received 1-2 cycles of platinum/taxane IC followed by standard definitive CRT. Peripheral blood was collected biweekly during IC and weekly during CRT to measure cfHPV DNA levels using HPV-SEQ, a CLIA-certified assay that uses SafeSEQ technology to sensitively detect and quantify HPV16 and HPV18 DNA in plasma (Sysmex Inostics). The treating radiation oncologist delineated tumor volumes on pre- and post-IC CT simulation scans. <h3>Results</h3> At present, 86 plasma samples have been examined across 12 enrolled patients. The median age was 65 years (range: 35-79). The primary disease sites included 8 oropharynx (OPX), 2 nasopharynx, 1 sinonasal, and 1 larynx, with all tumors being high-risk HPV positive by in-situ hybridization. All patients had at least cT3 disease or cN3 disease by AJCC 8 criteria, with 7 patients having cT4 disease. Half of the patients have a >10 pack-year smoking history. Tumor volume measurements and cfHPV DNA levels at key time-points for the 8 patients who have completed IC are summarized in Table 1 below. <h3>Conclusion</h3> Serial cfHPV DNA may provide an earlier and more quantitative readout of individualized treatment responsiveness compared with imaging assessment alone in HPV-related HNC. We identify a group of patients with locally advanced disease who had complete or near-complete cfHPV DNA clearance during IC. Rapid and effective clearance of cfHPV DNA may ultimately serve as a preferred metric for identifying "exceptional responders" who are ideal biological candidates for short-course CRT after IC. Our granular cfHPV DNA dataset with biweekly measurements during IC and weekly measurements during CRT should lead to a more precise evaluation of cfHPV DNA clearance velocity and tumor response kinetics with this paradigm.