Multimodality detection of early relapse in radically treated high-risk HPV-negative head and neck squamous cell carcinoma: study protocol for a prospective multicentre UK cohort study (HERD).

INTRODUCTION

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally, with over 12 000 new cases annually in the UK. Despite aggressive radical treatment, approximately 50% of patients with locally advanced (stage III/IV), human papilloma virus (HPV)-negative disease relapse within 2 years, often in the first year. Although current post-treatment follow-up schedules are recommended by clinical guidelines, imaging surveillance is led by symptoms after the initial 3 months and reliable biomarkers for early relapse are lacking. Consequently, recurrences are frequently detected too late for surgical salvage, though timely surgery can improve survival by up to 73% in selected cases. Head and Neck Early Relapse Detection Study represents a large-scale, prospective effort to integrate imaging, genomic, immunologic and microbiome datasets for relapse risk stratification and post-treatment surveillance in this high-risk patient group.

METHODS AND ANALYSIS:

Design

Prospective, observational cohort study.

SETTING

Secondary and tertiary NHS hospitals in the UK.

PARTICIPANTS

Recruiting up to 200 patients with stage III/IV (high-risk) HPV-negative HNSCC. Participants are enrolled into discovery (n=100) and validation (n=100) cohorts. Patients with HPV-positive tumours, metastatic disease or other contraindications defined in the protocol will be excluded.

INTERVENTIONS: Observational study with no experimental intervention. Participants are followed for 2 years with longitudinal collection of blood, saliva, urine, stool, fresh and archival tumour tissue and advanced MRI where possible in addition to their standard of clinical care.

PRIMARY OUTCOMES: Development and independent validation of a multimodal recurrence risk prediction model.

SECONDARY OUTCOMES: Identifying patient populations for primary treatment stratification, establishment of a longitudinal biorepository and identifying biological mechanisms of recurrence. Multimodal data will be integrated using machine learning and Bayesian modelling.

ETHICS AND DISSEMINATION: Ethical approval was granted by the Bromley Research Ethics Committee (21/PR/1581). Findings will be disseminated through peer-reviewed publications, conference presentations and scientific meetings.

TRIAL REGISTRATION NUMBER: NCT05097625.