Towards smart and personalized management of cervical cancer: Understanding oncological drivers in cervical malignancies to identify new avenues for nano- and immunotherapeutic treatment

In this thesis, the improvement of cervical cancer management has been explored through a dual approach: firstly, through examining patient-specific characteristics, such as human papillomavirus (HPV) viral load, to better predict clinical outcomes, and secondly, advancing targeted therapeutic interventions through innovative nanotechnology.

Since HPV is a causal factor for cervical cancer development, HPV viral load, the abundance of HPV DNA in tumor samples, has emerged as a crucial biomarker, correlating with increased metastasis, recurrence, and reduced survival probabilities due to its association with local immune suppression.

Concurrently, the development of targeted therapies, such as anti-PD-L1-functionalized immunoliposomes, has demonstrated promise in advanced in vitro models, achieving enhanced delivery and improved efficacy in a cervical cancer-on-a-chip model. Similarly, we have explored uses of other innovative nanotherapeutic platforms, including lipid-based nanoparticles, against critical challenges such as off-target toxicity and low tumor accumulation, enhancing immune modulation and targeting of the tumor microenvironment. We also explore potential uses of biomimetic nanoparticles (BMNPs) in cancer theranostics, but note that their application in cervical cancer remains limited by ethical and scalability concerns at this early stage, even with the positive outcomes seen in fundamental testing.

By integrating patient-tailored biomarkers like HPV viral load with next-generation nanotherapeutics, cervical cancer treatment paradigms can achieve improved personalization and efficacy, offering hope for better clinical outcomes.