Survival outcomes in head and neck squamous cell carcinoma of unknown primary: A national cohort study

John C Hardman; James Constable; Sian Dobbs; Christopher Hogan; Kate Hulse; Shivun Khosla; Kristijonas Milinis; Ben Tudor-Green; Andrew Williamson; Vinidh Paleri; INTEGRATE (The UK ENT Trainee Research Network)

doi:10.1111/coa.14167

Survival outcomes in head and neck squamous cell carcinoma of unknown primary: A national cohort study

Clin Otolaryngol. 2024 May 20. doi: 10.1111/coa.14167. Online ahead of print.

Collaborators

INTEGRATE (The UK ENT Trainee Research Network):
Panagiotis Asimakopoulos, Fergus Cooper, Prerana Rao, Katharine Davies, Timothy Davies, Stephen Derbyshire, Chuanyu Gao, Chiugo Ike, Maged Abdelkader, Christopher Hogan, Paul Spraggs, Anthony Bashyam, Jamie Patel, Oliver Dale, Laura Brennan, Mark Puvanendran, Billy Lk Wong, Tanzime Ahmed, Jemy Jose, Emma Molena, Stuart C Winter, James Rudd, Caroline Anderson, Waqqas Patel, Arcot Maheshwar, Haran Devakumar, Bhavesh Tailor, Ramesh Gurunathan, Gavin Donaldson, Paul Counter, Ayla Tabaksert, Trung Ton, Chang Woo Lee, Rajeev Srinivasan, Muhammad Hamza Qureshi, Richard Williams, Natasha Keates, Molly Jones, Ethne Grey-Still, Karan Kapoor, Anusha Balasubramanian, Nathan Anorson, Alex Bowen, Sian Dobbs, James O'Hara, Lepa Lazarova, Tom Bradish, Aoife Waters, Lisa Pitkin, Shivun Khosla, Stephanie Germain, Vinod Prabhu, Priyanka Shastri, Malcolm Buchanan, Theofano Tikka, Anna Loroch, Jean-Pierre Jeannon, Jack Faulkner, Mriganka De, Rodney Rodrigues, George Garas, Andreas Hilger, Tharsika Myuran, Dana Low, Basil Al Omari, Rachael Collins, James Moor, Mark Williams, Amy Round, Alexander Chadha, Oladejo Olaleye, Rishi Vasanthan, Quentin Bonduelle, Sultan Hatab, John Shotton, Nadine Caton, Syed Shah, Jaiganesh Manickavasagam, Ross Bannon, Estelle How Hong, Mrinal Supriya, Jacob Thoppil, Emma King, Andrew McGaughey, Neil Sharma, Hannah Nieto, Daniel Snelson, Paul C Nankivell, Jenny Montgomery, Kate Hulse, Christy Moen, Kishan Ubayasiri, Alex Charlton, Nada Dwiddar, Zach Shellman, Athena Togo, Sam Arman, Antonio Belloso, Fatima Seedat, Elliot Heward, Sarah Knowles, Venkat Reddy, Clare Perkins, Mouli Doddi, James Heyman, Alison Zander, Hannah Collins, Andrew Harris, Christian Johnatty, Nigel Beasley, Adam Gaunt, Natasha Quraishi, Ajith George, Ahmad K Abou-Foul, Saumil Shah, David Walker, Kenneth Lai, Chi Ike, Chuanyu Gao, Rony Raju, Stuart Gillett, Victoria Harries, Andrew Carswell, Georgina Wellstead, Ramzan Ullah, Jonathan Smith, Andrea Zuccarelli, Konstantinos Marinakis, Shraddha Jain, Jonathan Philpott, Javier Ash, Oliver Sanders, Iain J Nixon, Justin Yeo, Mamoona Khalid-Raja, Anastasha Herman, Shane Lester, Tobias James, Vinidh Paleri, John C Hardman, Paul Stimpson, Peter Lion, Ankit Patel, Richard Townsley, Andrew Williamson, Ian Smillie, Christy Moen, Mehaab Jaffer, Sandeep Berry, Laura Burton, Charlie Holden, Marcos Martinez Del Pero, Jeremy Wong, Andrew Mizen, Ram Moorthy, Haleema Siddique, Haroen Sahak, Robert Hone, Sheikh Momin, Rohit Kumar, Emma Gosnell

Affiliations

¹ Head and Neck Unit, The Royal Marsden Hospital, London, UK.
² Department of Otolaryngology, Head and Neck Surgery, Gloucestershire Royal Hospital, Gloucester, UK.
³ Manchester Royal Infirmary, Manchester Foundation Trust, Manchester, UK.
⁴ Department of Otolaryngology, Head and Neck Surgery, Basildon University Hospital, Basildon, UK.
⁵ Department of Otolaryngology, Head and Neck Surgery, Queen Elizabeth University Hospital, Glasgow, UK.
⁶ Department of Otolaryngology, Head and Neck Surgery, Royal Surrey County Hospital, Guildford, UK.
⁷ Liverpool Head and Neck Centre, Liverpool University Foundation Trust, Liverpool, UK.
⁸ Department of Otorhinolaryngology-Head & Neck Surgery, Derriford Hospital, Plymouth, UK.
⁹ Department of Otolaryngology, Head and Neck Surgery, Monklands University Hospital, Glasgow, UK.

PMID: 38766691
DOI: 10.1111/coa.14167

Abstract

Introduction: To investigate factors influencing survival in head and neck squamous cell carcinoma of unknown primary (HNSCCUP).

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 within 3 months of diagnosis with metastatic cervical squamous cell carcinoma. Patients treated as HNSCCUP underwent survival analysis, stratified by neck dissection and/or radiotherapy to the ipsilateral neck, and by HPV status.

Results: Data were received from 57 centres for 965 patients, of whom 482 started treatment for HNSCCUP (65.7% HPV-positive, n = 282/429). Five-year overall survival (OS) for HPV-positive patients was 85.0% (95% CI 78.4-92.3) and 43.5% (95% CI 32.9-57.5) for HPV-negative. HPV-negative status was associated with worse OS, disease-free (DFS), and disease-specific (DSS) survival (all p < .0001 on log-rank test) but not local control (LC) (p = .16). Unilateral HPV-positive disease treated with surgery alone was associated with significantly worse DFS (p < .0001) and LC (p < .0001) compared to radiotherapy alone or combined modalities (5-year DFS: 24.9%, 82.3% and 94.3%; 5-year LC: 41.8%, 98.8% and 98.6%). OS was not significantly different (p = .16). Unilateral HPV-negative disease treated with surgery alone was associated with significantly worse LC (p = .017) (5-year LC: estimate unavailable, 93.3% and 96.6%, respectively). Small numbers with bilateral disease precluded meaningful sub-group analysis.

Conclusions: HPV status is associated with variable management and outcomes in HNSCCUP. Unilateral neck disease is treated variably and associated with poorer outcomes when managed with surgery alone. The impact of diagnostic oropharyngeal surgery on primary site emergence, survival and functional outcomes is unestablished.

Keywords: human papillomavirus; neck dissection; neoplasm metastasis; squamous cell carcinoma of head and neck; unknown primary neoplasms.

Grants and funding

ENTUKFRG001/ENT UK Foundation Research Grants Programme