The role of non‐oropharyngeal biopsies in head and neck squamous cell carcinoma of unknown primary: A systematic review

Introduction This systematic review aims to evaluate the role of biopsies in non‐oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP). Methods This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Articles that encompassed non‐oropharyngeal biopsies in HNSCCUP as part of the diagnostic work‐up were selected and analysed. Results A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non‐targeted biopsies of non‐oropharyngeal sub‐sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%–9%) of non‐oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%–16.6%) from non‐oropharyngeal subsites. The primary site identified for Epstein–Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%–91%) helps in the detection of primaries to target biopsies in non‐oropharyngeal subsites. Conclusions On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non‐oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV‐positive metastasis. Where available, NBI should be used to help detect and target biopsies in non‐oropharyngeal subsites.