Clinicopathological Characterisation and Optimal Multidisciplinary Treatment of Cutaneous Head and Neck Melanoma in the Era of Effective Systemic Therapy

Abstract

Melanoma is dubbed the “National Cancer of Australia”. Despite extensive public health efforts focused on prevention, its incidence is steadily increasing. In 2025 there were an estimated 17443 new melanoma diagnoses in Australia and 1455 deaths. The field of melanoma oncology is continuously and rapidly evolving, with significant paradigm shifts in the last two decades. Major advances in sentinel node biopsy and systemic therapy, particularly the now-widespread use of targeted therapy and immunotherapy, have resulted in large improvements in staging, prognostication and survival outcomes for melanoma.

In this context, melanoma is increasingly recognised as a clinically and pathologically heterogeneous disease, but current treatment strategies remain largely based on histopathological and limited molecular criteria. There is currently conflicting evidence in the literature surrounding whether primary cutaneous head and neck melanoma (CHNM) may represent a distinct clinicohistopathological entity or behave similarly to cutaneous melanomas of other sites (CMOS).

This thesis aims to characterise the differences in clinicopathological features, prognosis, and outcomes between CHNM and CMOS, identify contributing mechanisms, and evaluate the ongoing role of surgery in the management of CHNM in the era of effective systemic therapy (defined in this thesis as BRAF-targeted therapy and/or immune checkpoint inhibitor immunotherapy). It takes the reader on a journey from the preclinical science through to the clinical management of melanoma from early stage to regional metastatic disease and finally distant metastatic disease.