(0633) Development of Oropharyngeal Tumor Organoids for Disease Modeling and Investigation of Treatment De-Escalation

Introduction: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with approximately 550,000 new cases diagnosed each year. Human papilloma virus (HPV) is a common cause of HNSCC, giving rise to a distinct subset of tumors with a different clinical presentation, disease course, and response to treatment. We aim to develop a preclinical model that allows for high throughput drug screening and radiation therapy to identify novel treatment strategies for HPV+ HNSCC.

Methods: To characterize HPV+ HNSCC tumors and their therapy response, we have leveraged our high throughput 3D tumor organoid screening platform. Our approach entails seeding tumor cells in extracellular matrix gels deposited around the perimeter of tissue culture wells in ring-like structures, with screening results available within a week from surgery. We particularly focused on oropharyngeal tumors, and developed organoids from both HNSCC and contralateral normal tonsil tissue. The tumor organoids are then treated with a combination of chemotherapy agents and radiation.

Results: We procured 57 patient samples from 32 patients (in cases of tonsil primaries, both tumor tissue and contralateral normal tissue were acquired) to develop organoids, performed high throughput drug screening, and completed immunohistochemical characterization including H&E staining, Ki67, p16 and p53 immunohistochemical staining. Given the importance of radiation as a treatment modality for HPV+ HNSCC, we have also optimized a chemoradiation pipeline to test possible combinatorial effects. Tumor organoids derived from HNSCC cell lines were exposed to several doses of radiation to identify the dose at which the tumors demonstrate radiosensitivity.

Conclusions: Taken together, our results demonstrate that 3D organoids of HNSCC generated from patient samples can successfully preserve native tissue characteristics and can be used for high throughput drug screening and radiation de-escalation testing, affording critical insight into the management of HNSCC in patients.