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.