Circulating human papillomavirus DNA as a surveillance tool in head and neck squamous cell carcinoma: A systematic review and meta‐analysis

• Published in: Clinical otolaryngology 2018-10, Vol.43 (5), p.1242-1249
• Main Authors: Jensen, K.K., Grønhøj, C., Jensen, D.H., von Buchwald, C.
• Format: Article
• Language: English
• Subjects: Biomarkers; Blood; Blood tests; Cancer; Demographic variables; Demographics; Deoxyribonucleic acid; Diagnostic systems; DNA; Head & neck cancer; Human papillomavirus; Literature reviews; Meta-analysis; mouth; oropharynx; Sensitivity; Squamous cell carcinoma; Surveillance; Systematic review; systematic reviews; tonsil
• ISSN: 1749-4478; 1749-4486
• DOI: 10.1111/coa.13136

Background The incidence of human papillomavirus‐induced (HPV+) head and neck squamous cell carcinoma (HNSCC), that is, especially oropharyngeal cancers (OPSCC), is increasing, and a significant proportion of patients encounter disease progression. A simple and sensitive test to identify patients with progression is an unmet need. Objective of Review To systematically review the literature and carry out a meta‐analysis of studies, investigating circulating HPV‐DNA as a biomarker for disease progression in patients with HNSCC. Type of Review A systematic review and meta‐analysis. Search Strategy PubMed, EMBASE and the Cochrane Library were systematically searched for articles published in English from January 1980 to November 2017. Search terms used were related to HPV, cancer sites, blood‐based biomarkers and terms for specific use settings. Evaluation Method Articles reviewed and selected by authors and data on study design, demographic variables, location, HPV status, number of pre‐treatment blood tests, number of post‐treatment blood tests, blood HPV status and number of recurrences and length of follow‐up were extracted. A meta‐analysis of HPV‐DNA as a diagnostic test for recurrence by means of a hierarchical summary receiver operating curve (HSROC) model was performed. Results We identified 5 studies (n = 600 subjects) examining circulating HPV‐DNA in patients with HNSCC. In these 5 studies (n = 411), patients had both pre‐ and post‐treatment blood samples. The pooled sensitivity, in detecting a recurrence, was estimated to be 54% (95% CI: 32%‐74%), while the pooled specificity was 98% (95% CI: 93%‐99.4%). The pooled false‐positive rate is 2% (95% CI: 0.6%‐7%). The area under the curve (AUC) of the summary HSROC was 0.93. Positive predictive value was estimated to 93% and the negative predictive value to 94%. Conclusions Plasma HPV‐DNA is a promising tool for surveillance in patients with HPV‐related HNSCC, that is, OPSCC, and has a high specificity. By recent technical advances and by increasing follow‐up blood samples, the sensitivity could likely be improved.