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Observational Study
. 2025 May;50(3):462-473.
doi: 10.1111/coa.14272. Epub 2025 Jan 8.

Investigations for Suspected Head and Neck Squamous Cell Carcinoma of Unknown Primary (HNSCCUP): A National Cohort Study

John C Hardman  1 , James Constable  2 , Andrew Williamson  3 , Sian Dobbs  4 , Christopher Hogan  5 , Kate Hulse  6 , Shivun Khosla  7 , Kristijonas Milinis  8 , Ben Tudor-Green  9 , Vinidh Paleri  1 ; INTEGRATE (The UK ENT Trainee Research Network)
Collaborators, Affiliations
Observational Study

Investigations for Suspected Head and Neck Squamous Cell Carcinoma of Unknown Primary (HNSCCUP): A National Cohort Study

John C Hardman et al. Clin Otolaryngol. 2025 May.

Abstract

Objectives: Head and neck squamous cell carcinoma from unknown primary (HNSCCUP) is a rare and challenging condition. This study aimed to investigate the diagnostic pathways of suspected HNSCCUP patients in the United Kingdom.

Methods: A retrospective observational cohort study was conducted, over 5 years from January 2015, in UK Head and Neck centres of consecutive adults undergoing 18F-Fluorodeoxyglucose-PET-CT (PET-CT) within 3 months of diagnosis with metastatic cervical squamous cell carcinoma. Patients with no primary site on examination and no previous head and neck cancer were eligible.

Results: Data for 965 patients were received from 57 centres; 68.5% were HPV-related disease. Three investigation cycles were observed: ultrasound with biopsy, cross-sectional imaging (MRI and/or CT) and PET-CT, at median times of 17, 29.5 and 46 days from referral. No primary was identified on PET-CT in 49.8% (n = 478/960). Diagnostic tonsillectomy was performed in 58.2% (n = 278/478) and tongue base mucosectomy (TBM) in 21.7% (n = 104/479). Ipsilateral tonsillectomy carried the highest diagnostic yield (18.7%, n = 52/278), followed by TBM (15.4%, n = 16/104). Contralateral tonsillectomy, performed in 49.0% (n = 234/478), carried the lowest yield (0.9%, n = 2/234). PET-CT with concurrent MRI was associated with higher primary site detection than PET-CT with concurrent CT (p = 0.003). A minority of patients undergoing treatment with curative intent received first-definitive-treatment within 62 days of referral (15.2%, n = 77/505, median 92 days, IQR: 71-117).

Conclusions: Most patients experienced a protracted diagnostic pathway and waited over 3 months for definitive treatment. Earlier PET-CT with concurrent MRI may expedite diagnosis. TBM appears more productive than contralateral tonsillectomy for primary site detection.

Keywords: clinical audit; lingual tonsillectomy; national targets; oropharyngeal cancer; treatment delays.

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References

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