PhD defence S. (Selin) Tokez

Dissertation in short:

In this thesis, we covered the full spectrum of cutaneous squamous cell carcinoma (cSCC) epidemiology, ranging from its in situ form up to metastasized disease. We did this by using several (nationwide) data sources, from both the Netherlands and England, and multiple data linkages across cancer, pathology, and organ transplant registries. We showed that incidence rates for cSCC - which is the second most common cancer worldwide - are still increasing for both cSCC in situ and invasive cSCC. We also showed that 1.9% of ~11,000 patients with a first cSCC developed metastasis during a median of 1.5 years. Risk factors were male sex, age, and immunosuppression. Additionally, we investigated tumor-based risk factors for metastatic cSCC and replicated these in a geographically separate cohort. Important risk factors were tumor diameter, thickness, poor differentiation, invasion in/beyond subcutaneous fat, facial localization, and perineural/lymphovascular invasion. Furthermore, we externally validated four current staging systems and showed that there is room for improvement to correctly discriminate between cSCCs at high and low risk for metastasis. Using a population-based study in elderly with actinic keratosis (AK), we showed that the number of AKs, their localization, and coffee consumption are predictors for keratinocyte carcinoma development in this patient group. Finally, we performed a diagnostic study among patients with a high-risk cSCC of the head and neck: baseline ultrasonography had a high sensitivity for detecting lymph node metastasis in patients with a negative result at clinical examination, but this sensitivity should be evaluated against the many false-positive findings.