PI: Giovanni Blandino
Other IRE Principal Collaborators Involved:Sabrina Strano, Anna Teresa Bagnato, Giuseppe Sanguineti, Sara Donzelli, Piera Tocci

Project duration: 24 months

Project code: PNRR-POC-2022-12376580

Head and neck squamous cell carcinomas (HNSCC) are characterized by high heterogeneity, late-stage diagnosis, local invasiveness, and frequent relapses, leading to a low survival rate. These poor outcomes are partly due to the lack of cost-effective diagnostic methods and efficient patient monitoring tools. Current tissue biopsies often fail to capture the molecular diversity and ongoing evolution of metastatic tumors.

This project aims to establish non-invasive diagnostic tools by analyzing circulating tumor DNA and RNA (ctDNA/RNA) from blood and saliva samples. These liquid biopsies provide the opportunity to monitor tumor changes and extract real-time molecular information. Specifically, the study focuses on establishing reliable human papillomavirus (HPV) viral DNA and host DNA/RNA biomarkers to detect early relapse and provide early prognostic characterization for HNSCC patients.

The proposal builds on a patented miRNA signature developed by the National Cancer Institute in Rome (INCI) in 2020. The study will evaluate this miRNA signature and HPV viral DNA as biomarkers for early relapse in two patient cohorts:

Retrospective Cohort: Conducted at INCI in Rome, evaluating relapse predictive potential using baseline samples from tumor, peritumoral, and non-tumoral tissues. Validation will also occur using blood and saliva samples. This cohort includes 30 relapses from 150 patients, followed up at 6, 12, 18, 24, and 36 months post-surgery.

Prospective Cohort: Involves patient recruitment at INCI in Rome, Bari, and Milan University to achieve a larger sample size (550 patients across 4 hospitals, with an estimated 105 relapses). This cohort will validate findings from the retrospective study over a 20-month period, aligning with the end of the proposed project.

The primary purpose of this project is to develop and validate non-invasive biomarkers for the early detection of HNSCC relapse using liquid biopsies. By leveraging HPV viral DNA and host DNA/RNA biomarkers in blood and saliva, the study aims to improve early diagnostic accuracy and patient monitoring. This approach is expected to enhance clinical decision-making and personalized treatment strategies for HNSCC patients.

Validation of Biomarkers: Establishment of circulating miRNAs and HPV DNA as reliable predictors of HNSCC recurrence.

Standardized Methodology: Development of a standardized approach for simultaneous assessment of circulating HPV DNA and miRNAs, enabling integration into clinical practice.

Clinical Impact: Improved early relapse detection, leading to enhanced long-term survival rates, reduced morbidity, and minimized treatment burdens for HNSCC patients.

Scientific Advancement: Contribution to the understanding of molecular mechanisms underlying HNSCC relapse, facilitating future biomarker discovery and personalized oncology.