Gabriel Johansson

Doctoral project: Nodal metastatic burden in oral cancer: from occult disease to immunotherapy-induced remodelling

Principal supervisor: Rusana Bark

Co-supervisors: Krzysztof Piersiala, Linda Marklund, Martin Hysek

Background: Lymph node metastasis is a major prognostic factor in oral squamous cell carcinoma (OSCC). In the last decade, sentinel lymph node biopsies have become an established part of the management of early-stage OSCC, and at Karolinska University Hospital the technique is applied also in advanced-stage disease. Since its introduction in head and neck cancers, sentinel lymph node biopsy has facilitated the detection of microscopic tumour deposits in cervical lymph nodes. However, the clinical importance of micrometastasis (lymph node metastases smaller than 2 mm) remains uncertain. We cannot reliably identify which patients are at risk of progression, and there is no consensus on management strategies.

Neoadjuvant PD-1 blockade has recently emerged as a promising treatment option in resectable, locally advanced head and neck cancer, and pathological response is associated with survival. Response is mostly assessed in the primary tumour, whereas regression in the cervical lymph nodes may follow a different pattern and could carry independent prognostic information.

Aims: The overall aim of my research is to improve risk stratification and therapeutic decision-making in OSCC. Across five studies, this will be addressed by investigating the prognostic impact of lymph node micrometastasis, analysing management strategies in micrometastatic disease, evaluating sentinel node-guided strategies in advanced disease, systematically characterising nodal response patterns to neoadjuvant immunotherapy, and studying the immune microenvironment of micrometastatic lymph nodes.