Abstract
Simple SummaryHuman 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.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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) presents the sixth most common malignancy worldwide and approximately 700,000 new cases are diagnosed each year [1]
We obtained 16 records for systematic review (Table 1). Out of these 16, 10 diagnostic studies were eligible for quantitative meta-analysis at first diagnosis of disease (Table 1, marked #), whereas five out of those 16 studies were eligible for analysis of cfHPV-DNA detection during follow-up (Table 1, marked **)
We found that p16 staining alone and a combined approach demonstrated a higher level of sensitivity and specificity than
Summary
Head and neck squamous cell carcinoma (HNSCC) presents the sixth most common malignancy worldwide and approximately 700,000 new cases are diagnosed each year [1]. Incidences of oropharyngeal squamous cell carcinoma (OPSCC) are rising as a result of an increasing prevalence of high-risk human papillomavirus (HPV)-related tumors and rates have already surpassed those of cervical cancer in some developed countries [2,3,4,5]. Dependent on the geographical region, 40–80% of OPSCC are HPV-related, whereas in other head and neck subsites, rates are estimated below 5% [6]. Up to 25% of patients develop local/regional recurrent disease or distant metastasis following established therapy concepts and present with 5-year overall survival rates comparable to those observed in HPV-negative
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