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

Abstract

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. 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. 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. 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. 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.