Impact of circulating tumor human papillomavirus DNA kinetics on disease outcomes in HPV‐associated oropharyngeal cancer

Circulating tumor tissue modified (TTMV)-HPV DNA has emerged as a promising biomarker in human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV-OPSCC). The objective of this study was to assess ctHPVDNA TTMV clearance kinetics during RT and its relationship with progression in HPV-OPSCC. We identified 80 non-metastatic HPV-OPSCC patients with 366 TTMV samples who underwent prospective plasma TTMV testing before, during and after curative intent RT or CRT between June 2021 and February 2023. Patients with rapid favorable clearance (>95% decline from pre-treatment value) of TTMV were compared to those with suboptimal clearance (<95%). The primary objective was to evaluate the relationship between TTMV clearance during CRT and its impact on progression free survival (PFS). The median follow-up was 14.7 months. Clinical nodal stage was associated with higher TTMV-HPV DNA scores at baseline, with a median score of 128, 778, and 1219 for N0/N1, N2a/b, and N2c/3 patients, respectively. Patients who had persistent TTMV at the end of RT had an inferior PFS compared to those who cleared their TTMV at 2 years (91.7% vs. 71.7%) (log rank, p = .042). Among patients who had complete clearance of their TTMV at 3 months, those who had a negative, equivocal, and incomplete PET response had a 2-year PFS of 94.3%, 77.8%, and 59.3%, respectively (log-rank, p = .029). Our study indicates that persistent TTMV-HPV DNA is associated with worse PFS and may portend unfavorable outcomes. Thus, monitoring TTMV clearance kinetics could be a valuable biomarker for guiding treatment decisions in patients with HPV-OPSCC.