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.