Cell-Free HPV-DNA as a Biomarker for Oropharyngeal Squamous Cell Carcinoma—A Step Towards Personalized Medicine?

SIMPLE SUMMARY: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is a distinct tumor entity with relatively favorable overall survival. Nevertheless, up to 25% of HPV-related OPSCC patients develop recurrent or metastatic disease with a fatal outcomes. Biomarkers to enable early diagnosis and to monitor this disease are not established. Liquid biopsy presents a promising minimally invasive method to monitor the cell-free DNA of oncogenic HPV and to enable personalized therapy concepts. Few studies have investigated the role of cell-free HPV DNA (cfHPV-DNA) as a diagnostic marker in patients with OPSCC with variable outcomes. To emphasize the importance of cfHPV-DNA, we performed a literature review and meta-analysis. Our results demonstrate that cfHPV-DNA in patients with OPSCC presents a promising diagnostic tool with high specificity. Nevertheless, further studies with homogeneous inclusion criteria will be necessary to strengthen the role of cfHPV-DNA as a biomarker in the future. ABSTRACT: Global incidences of oropharyngeal squamous cell carcinoma (OPSCC) are rising due to an association with high-risk human papillomavirus (HPV). Although there is an improved overall survival of HPV-related OPSCC; up to 25% of the patients develop recurrent or distant metastatic disease with a fatal outcomes. Biomarkers to monitor this disease are not established. This meta-analysis reviews the role of cell-free HPV DNA in liquid biopsy (LB) as a biomarker for HPV-related OPSCC. Pubmed, Livivo, and Cochrane Library databases were searched from inception to August, 2020. All studies were analyzed by Meta-DiSc 1.4 and Stata 16.0 statistical software. In total, 16 studies were considered for systematic review, whereas 11 studies met inclusion criteria for meta-analysis, respectively. Pooled sensitivity of cfHPV-DNA at first diagnosis and during follow-up was 0.81 (95% CI; 0.78–0.84) and 0.73 (95% CI; 0.57–0.86), while pooled specificity was 0.98 (95% CI; 0.96–0.99) and 1 (95% CI; 0.99–1). The diagnostic odds ratio (DOR) at first diagnosis was 200.60 (95% CI; 93.31–431.22) and 300.31 (95% CI; 60.94–1479.88) during follow-up. The area under the curve (AUC) of summary receiver operating characteristic (SROC) was 0.99 at first diagnosis and 1.00 during follow-up, respectively. In conclusion, cfHPV-DNA presents a potential biomarker with high specificity in patients with HPV-related OPSCC.