The role of ctDNA from liquid biopsy in predicting survival outcomes in HPV-negative head and neck cancer: A meta-analysis

The incidence of head and neck cancer (HNC) is on the rise, making it a significant clinical challenge. Human papillomavirus (HPV)-related and HPV-negative HNC exhibit distinct etiopathogenesis and prognoses, requiring targeted approaches for effective management. Conventional tissue biopsies are essential for confirming the diagnosis and locating solid tumors. However, they have limitations in detecting microscopic disease, tracking treatment response, and capturing the dynamic heterogeneity of the mutational profile within the tumor. Liquid biopsy using circulating tumor DNA (ctDNA) analysis has emerged as a promising non-invasive tool to overcome the drawbacks of conventional biopsy for comprehensive molecular profiling.

This meta-analysis aims to colligate available evidence on the clinical utility of ctDNA analysis in predicting survival outcomes, specifically in HPV-negative HNC. Our systematic search of six electronic databases identified eight publications (N = 886 patients) meeting the inclusion criteria. The included studies reported data from HPV-negative HNC patients, employing ctDNA analysis to report survival outcomes. Our findings reveal a significant association between mutation or methylation in ctDNA and worsened survival outcomes in HPV-negative HNC cases. The presence of ctDNA mutations in TP53 and methylation of SEPT9 and SHOX2 was linked to reduced overall survival, disease-free survival, and progression-free survival. Subgroup analyses demonstrated consistent associations across different survival outcomes, ctDNA detection methods, and blood collection tubes used.

Our study underscores the need for future research endeavors prioritizing larger, well-designed prospective studies with standardized methodologies to further elucidate the role of ctDNA analysis in guiding personalized treatment approaches and optimizing patient care in this specific HNC cohort.