Indications for oropharyngeal biopsy in head and neck squamous cell carcinoma of unknown primary: A systematic review (HNSCCUP)

Introduction: Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary. Objective: The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP. Method: Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Results: A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author - table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative. Conclusions: High level evidence is lacking, with heterogeneity in the reported studies. Published meta-analyses are based on retrospective data. There is little evidence supporting the practice of random/non-directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies.