Plasma HPV ctDNA as a dynamic biomarker for treatment response and prognosis in locally advanced cervical cancer: protocol for a prospective cohort study.

BACKGROUND: Locally advanced cervical cancer (LACC) remains a major global health burden, and current imaging-based assessment after standard concurrent chemoradiotherapy (CCRT) is limited by delayed detection of treatment failure and poor sensitivity for microscopic residual disease. Circulating human papillomavirus DNA (HPV ctDNA) represents a tumor-specific biomarker with potential for real-time treatment monitoring. This prospective cohort study aims to evaluate whether dynamic monitoring of plasma HPV ctDNA can predict treatment response and prognosis in patients with LACC receiving CCRT. METHODS/DESIGN: This single-center, observational cohort study will enroll 57 patients with histologically confirmed LACC (FIGO 2018 stage IB2-IVA) and baseline high-risk HPV infection. All patients will receive standard CCRT including external beam radiotherapy (45-50.4 Gy), concurrent weekly cisplatin (40 mg/m²), and intracavitary brachytherapy. Peripheral blood samples (10 mL) will be collected at five predefined time points: baseline (T0), mid-treatment (T1), end of CCRT (T2), 3 months post-CCRT (T3), and every 6 months thereafter for 24 months. Plasma HPV ctDNA will be quantified using droplet digital PCR targeting HPV16/18 E6/E7 genes. The primary endpoint is progression-free survival (PFS), comparing patients with detectable versus undetectable ctDNA at 3 months post-CCRT. CONCLUSION: This study will provide prospective evidence for HPV ctDNA as a minimally invasive biomarker for treatment monitoring and prognostic stratification in LACC, potentially informing future risk-adapted therapeutic strategies.