Recurrence and Circulating Tumor DNA in Human Papillomavirus‐Positive Oropharyngeal Cancer: A Meta‐Analysis

OBJECTIVE: To perform a systematic review and meta-analysis on the utility of circulating tumor DNA (ctDNA) in serum as a biomarker for post-treatment surveillance of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), given the improved treatment response and 10% to 20% recurrence rate in this patient population. DATA SOURCES: Articles were sourced from PubMed. Studies were excluded if they focused on HPV-driven cancers in other anatomical regions, lacked pretreatment and posttreatment HPV viral load data, or were published more than 20 years ago. All literature available in English was considered. REVIEW METHODS: A PRISMA-compliant review identified 419 articles, and 20 studies met all inclusion criteria. Data extraction and quality assessment were performed using Oxford Centre for Evidence-Based Medicine and Newcastle-Ottawa Scale criteria. RESULTS: Across 3505 clinically correlated tests, pooled sensitivity was 80.3% (95% CI 70.9%-87.2%) and specificity was 95.5% (90.9%-97.8%). Meta-analysis of our studies found the overall prevalence of recurrent HPV + OPSCC after curative treatment was 9.70% (95% CI 8.72%-10.78%). Negative Predictive Value (NPV) at this prevalence was 97.7% (96.7%-98.5%) and Positive Predictive Value (PPV) was 66.0% (49.5%-80.3%). A positive test for ctDNA after curative treatment had a 130.3 (95% CI 56.60-298.71) fold higher odds of disease recurrence compared to a negative test. CONCLUSIONS: CtDNA is a promising biomarker for early detection of recurrence. Standardized protocols and quantitative thresholds are needed to fully establish its role in clinical practice.