INTRODUCTION
As alluded to throughout this special issue, diagnostic and treatment paradigms for head and neck squamous cell carcinoma of unknown primary (HNSCCUP) are vexed issues, reflecting a dearth of robust contemporary evidence on the topic. This is largely because true unknown primary disease is relatively uncommon (1-5 % of all HNSCC cases (1)), resulting in small study cohorts, particularly in single-centre settings, compounded by a lack of uniformity between studies on the definition of what constitutes an ‘unknown primary’, making inter-study comparisons or pooled-analyses challenging or indeed unfeasible. Furthermore, the relatively recent realisation of the importance of human papillomavirus (HPV) in HNSCC oncogenesis (2), the particular pertinence this has to HNSCCUP given the typical clinical presentation (that p16 positive HNSCCUP is considered oropharyngeal in the most recent edition of TNM/AJCC Classification for Head and Neck Cancer attests to this) (3), together with the dramatic upsurge HPV-related HNSCC (4), casts aspersion on the relevance of many historic studies to modern day practice.
An issue of contemporary interest in the management of HNSCCUP is in which specific circumstances can patients be managed by surgery as a single modality, thus avoiding adjuvant treatment and associated toxicity. The increased traction of this notion in recent years is underpinned, firstly, by advances in diagnostic surgical work-up resulting in more comprehensive oropharyngeal sampling, with tongue base mucosectomy becoming a standard of care in many centres internationally, and secondly, by a shift towards treatment de-escalation in HPV-related oropharyngeal SCC, something which is the subject of several international clinical trials currently recruiting (5,6)
Current guidelines internationally recommend that in HNSCCUP single-modality treatment can be considered in the presence of N1 or “small-volume” disease in the absence of extra-nodal extension (7–9). However, such recommendations are relatively tentative, suggesting multi-disciplinary discussion on an individual case basis; and are largely derived from consensus and expert opinion and/or extrapolation from contemporary oropharyngeal SCC data. To this end, to the best of our knowledge there have been no prior attempts to formally synthesise data on this topic to inform such decision-making.
Cognisant of these issues, the purpose of this systematic review was to collate and interrogate in detail the evidence for HNSCCUP patients treated with neck dissection (ND) alone with respect to oncological outcomes.