Aim: HPV-associated oropharyngeal cancer (HPV-OPC) is increasingly treated with de-escalated, multimodality regimens, creating a need for dynamic biomarkers of molecular residual disease (MRD) and recurrence. We evaluated circulating tumor DNA (ctDNA) kinetics as a biomarker of treatment response and recurrence in patients enrolled in NECTORS, a prospective neoadjuvant chemotherapy(NAC) and transoral robotic surgery (TORS) trial. Methodology: Paired plasma and saliva were collected at baseline, post-NAC (V1), post-TORS, and during surveillance in 56 HPV-OPC patients. ctDNA was quantified by droplet digital PCR (ddPCR) targeting the E7 region of 14 high-risk HPV genotypes. Kinetic patterns were categorized as rapid/early clearance, late clearance, persistent positive, or rebound (positive-negative-positive). Associations with residual disease at surgery and RFS were assessed. Results: Median follow-up was 27.8 months. Four recurrences were observed. All recurrence events occurred in patients with unfavourable plasma kinetics (3 rebound, 1 persistent positive) within 24 months post-treatment, whereas no recurrences were seen in rapid/early clearance, late clearance, or baseline-negative plasma groups. At V1, composite ctDNA positivity in plasma or saliva was associated with residual disease at surgery (14/16 [87.5%] composite-positive vs 16/34 [47.1%] composite-negative; OR 7.88, Fisher's exact p=0.012). Any surveillance plasma positivity was strongly associated with recurrence (sensitivity 100%, specificity 95.7%). Conclusion: In HPV-OPC, ctDNA kinetics stratify recurrence risk across the treatment continuum: pre-surgical composite positivity predicts residual disease, surveillance positivity identifies recurrence, and favourable clearance patterns confer stable disease control through 24 months. As a prospective proof-of-concept study, these findings support ctDNA-guided surgical decision-making and risk-adapted de-escalation, warranting validation in larger trials.