Materials and methods
A retrospective review was conducted of patients who had undergone
primary neck dissection (ND) for p16+ve OPSCC between 2015-2019 at our
institution. NDs were performed by two surgeons (JWM and AP), and all
patients underwent trans-oral surgery (TORS or TLM) of the primary
tumour either simultaneously or after a delay of 1-2 weeks depending on
logistical factors (availability of the surgical robot, for instance).
Inclusion criteria included primary tumours with positive p16
immunohistochemistry (IHC) affecting the tonsil, base of tongue and soft
palate, and patients for whom primary tumours were unidentifiable (for
whom p16 positivity was established in IHC from lymph node metastasis).
All patients with unidentifiable primary tumours underwent cross
sectional imaging and PET/CT scan, bilateral tonsillectomy, and base of
tongue mucosectomy to attempt to identify the primary site. Exclusion
criteria included any patient who had received any form of previous head
and neck cancer treatment, paediatric patients, non-oropharyngeal
primary tumours, and p16 negative or ‘p16 status unknown’ tumour
biology.
All neck dissections routinely include levels II-IV, with the ultimate
extent of surgery being guided by pre-treatment clinical and
radiological staging. Excised nodal levels are resected en bloc and
divided by the surgeon into separate specimens, each comprising a
specific neck level. Each level is sent separately to histopathology
fixed in formalin and processed according to an operating pathology
protocol that safeguards specimen orientation, laboratory sampling, and
the reporting of lymph nodes, extranodal extension, tumour margins and
soft tissue deposits6. For the purpose of this
analysis any patient who had separate specimens dissected from levels
IIA and IIB were combined into a single ‘Level II’ to ensure
consistency.
Assessments of clinical, radiological, and pathological reports were
undertaken for each patient. Each neck level was assigned a status of
clinically node-negative (cN0) or positive (cN+ve) and pathologically
node-negative (pN0) or positive (pN+ve). Occult nodal disease was
defined as the pathological presence of metastatic nodal disease in the
specimen with the absence of clinical or radiological disease specified
at the corresponding neck level. Thereafter, neck node level of clinical
and pathological disease statuses (cN0 or cN+ve, and pN0 or pN+ve) were
recorded and compared.
Staging utilised the American Joint Committee on Cancer (AJCC)
8th edition (TNM8) for p16+ve OPSCC. Clinical,
radiological, and pathological reports of patients staged using the AJCC
7th edition (TNM7) were reviewed to restage them
according to the TNM8 criteria. The clinical staging pathway following
clinical examination involves contrast-enhanced MRI of the neck and CT
of the chest. In a minority of cases PET/CT or CT was used to stage the
neck due to inability to undergo MRI.
Positive predictive values (PPV) and negative predictive values (NPV)
for cN+ve status in each neck level were calculated with 95% confidence
intervals (95% CI) via the use of Microsoft Excel and are based on the
chi-squared test for the ratios of two proportions.7,
8 For parametric data, the unpaired Student’s T test was used to assess
the means between groups, with statistical significance assumed if p
< 0.05.