PhD S. (Seth-Frerich) Fobian

Below is a brief summary of the dissertation:

Cervical cancer is caused by a prolonged infection with high-risk types of human papillomavirus (HPV). Early-stage cervical cancer patients are typically treated surgically, while patients with locally advanced tumors receive chemoradiotherapy or thermoradiotherapy. For recurrence or metastasis, chemotherapy, often combined with immunotherapy, is the treatment of choice. However, these treatments often have severe side effects, including reduced fertility. Less toxic and more targeted therapies are needed, with better risk identification and management.

In this research, we focused on improving diagnosis, risk stratification, and therapy. We explored the role of HPV viral load in cervical cancer and its precursors. Studies indicate that higher HPV levels per cell are linked to worse clinical outcomes, although there is no standardization in HPV measurement methods. This finding suggests HPV load could be a valuable biomarker for treatment selection and risk stratification.

We also studied 44 HPV-positive cervical cancer patients at Amsterdam UMC, finding that higher HPV loads correlated with worse survival, more frequent lymph node metastases, and lower immune cell presence in the tumor microenvironment.

We investigated lipid-based nanoparticles (LNPs) for delivering cancer immunotherapies, which could reduce toxicity and improve efficacy. LNPs can deliver immune modulators like cytokines and checkpoint inhibitors. Our research also examined targeted liposomes with PD-L1 inhibitors, which showed promising results in cervical cancer models.

Lastly, we highlighted biomimetic nanoparticles, which enhance biocompatibility, drug delivery, and tissue penetration, offering potential for improved cancer treatments. This research paves the way for smarter, more effective cervical cancer treatments and possibly other cancers.