PI: Antonello Vidiri
Other IRE Principal Collaborators Involved: Pellini Raul, Benevolo Maria, Flaminia Campo

Project duration: 24 months

Project code: PNRR-TR1-2023-12377980

This project addresses the need for improved methods to predict and monitor disease progression in oropharyngeal cancer (OPC), particularly HPV-related OPC. Current methods relying on clinical evaluation and imaging can lead to unnecessary procedures. This study proposes a multidimensional assessment of OPC patients before and after surgery, integrating radiomics (MRI analysis), circulating tumor HPV-DNA (ctHPV-DNA) detection, in-depth immunological profiling (tumor tissue and peripheral blood), extracellular vesicle (EV) analysis, and measurement of serum factors. Advanced bioinformatic tools will be used to identify biomarkers correlating with disease status.

Radiological Feature Evaluation: Define MRI-derived radiomic signatures that can differentiate between HPV+ and HPV- OPC and correlate with immunological features, locoregional tumor control, and distant metastasis.

Longitudinal Biomarker Evaluation: Measure ctHPV-DNA levels, perform deep immunophenotyping of tumor tissue, lymph nodes, and peripheral blood, analyze EVs in serum, and measure circulating serum factors longitudinally over 12 months of follow-up. This includes assessing HPV-specific T cell responses and innate immune responses.

Biomarker Identification and Validation: Correlate clinical, radiological, and experimental data using machine learning algorithms to identify and validate biomarkers predictive of disease progression and patient stratification.

Radiomic Signatures: Identification of MRI-derived radiomic signatures that can distinguish HPV+ from HPV- OPC and predict oncological outcomes.

ctHPV-DNA Dynamics: Characterization of ctHPV-DNA dynamics pre- and post-surgery and its correlation with disease status.

Comprehensive Immunological Profile: Detailed characterization of the in situ and systemic immune landscape in OPC, including HPV-specific T cell responses, innate immune cell populations, and circulating immune factors.

EV Characterization: Characterization of serum EVs, including size distribution and surface marker expression, and their potential as biomarkers.

Integrated Biomarker Panel: Development of an integrated panel of biomarkers (radiological, ctHPV-DNA, immunological, EV, and serum factors) that can predict disease progression and stratify patients for personalized treatment.

Improved Clinical Decision-Making: The project aims to provide clinicians with non-invasive tools for dynamic assessment of tumor burden, potentially reducing unnecessary procedures and improving treatment strategies.

Translational Insights: The data will provide translational evidence on harnessing the immune system for improved therapy efficacy and inform anti-HPV vaccination strategies.