Cell-Free Human Papillomavirus-DNA for Monitoring Treatment Response of Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Objectives/Hypothesis The aim of this study was to assess the value of cell-free human papillomavirus-DNA (cfHPV-DNA) as a diagnostic test for the post-treatment surveillance of patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) through a systematic review and meta-analysis. Study Design Systematic review and meta-analysis. Methods A literature search was conducted in three databases (MEDLINE, Embase, and Scopus) in January 2021. The population included patients with HPV-positive HNSCC. The intervention was the use of the repeated liquid biopsy with circulating HPV-DNA detection during follow-up. The outcome was to establish the value of cfHPV-DNA as a diagnostic test for the post-treatment surveillance of patients with HPV-positive HNSCC. Results Ten studies included in the meta-analysis provided a total of 457 patients with HPV-positive HNSCC. The meta-analytic study estimated the diagnostic performance of cfHPV-DNA as follows: pooled sensitivity and specificity of 0.65 (95% confidence interval [CI]: 0.40-0.84) and 0.99 (99% CI: 0.96-0.99), respectively; positive and negative likelihood ratios of 62.5 (99% CI: 22.9-170.2) and 0.05 (99% CI: 0.013-0.24), respectively; and pooled diagnostic odds ratio of 371.66 (99% CI: 60.4-2286.7). Conclusion Currently, the follow-up protocol for HNSCC patients includes routine clinical evaluation and radiological imaging. Biomarkers to monitor this disease are not established. Considering its high specificity, cfHPV-DNA represents a potential confirmatory test in the case of positive positron emission tomography and computed tomography. In the near future, cfHPV-DNA could be used as a biomarker for monitoring the treatment response during the clinical trials of de-escalation therapy or immunotherapy. Larger sample sizes and the homologation of study protocols and methodology are needed to better establish its utility in the clinical practice. Laryngoscope, 2021