ESTRO 2024 - Abstract Book

S5346

Radiobiology - Tumour biology

ESTRO 2024

792

Digital Poster

HPV and Radiochemotherapy in HNSCC: Insights from Transcriptomic and Epigenomic Analyses

Safayat Mahmud Khan 1,2 , Rosemarie Euler-Lange 1,2 , Soňa Michlíková 3,4 , Cylia Ouadah 3,4 , Wahyu W. Hadiwikarta 1,5 , Chiara Valentini 6 , Nadja Ebert 1,6,7 , Steffen Löck 3,4 , Mechthild Krause 3,4,6 , Michael Baumann 1,2,5 , Maria José Besso 1,2 , Ina Kurth 1,2,8 1 German Cancer Research Center (DKFZ), Division of Radiooncology / Radiobiology, Heidelberg, Germany. 2 Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation, Research in Oncology (NCRO), Heidelberg, Germany. 3 Helmholtz-Zentrum Dresden - Rossendorf, University Hospital Carl Gustav Carus, Technische Universität Dresden, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine-Zentrum Dresden - Rossendorf, Dresden, Germany. 4 Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany. 5 German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, Germany. 6 Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Department of Radiotherapy and Radiation Oncology, Dresden, Germany. 7 Faculty of Medicine, Helmholtz-Zentrum Dresden - Rossendorf, University Hospital Carl Gustav Carus, Technische Universität Dresden, OncoRay - National Center for Radiation Research in Oncology, Dresden, Germany. 8 German Cancer Consortium (DKTK), DKFZ, core center Heidelberg, Heidelberg, Germany Head and Neck Squamous Cell Carcinomas (HNSCC) originate from the mucosal linings of diverse anatomical locations in the upper aerodigestive tract exhibiting significant heterogeneity. Human Papillomavirus (HPV), a known risk factor for these cancers, has emerged as a favorable biomarker for prognosis after radiochemotherapy (RCT). In general, HPV infection, which occurs mainly in the oropharynx and tonsils, is associated with a better prognosis than HPV- HNSCC under the same treatment. Studies have also shown that the HPV+ subgroup has a higher risk of recurrence. In addition, their incidence steadily increases and, for instance, patient stratification is a crucial clinical need. A recent preclinical study comparing HPV+ and HPV- HNSCC xenografts treated with radiotherapy (RT) and RCT, showed that they exhibited heterogeneous response in terms of local tumor control [1]. Existing research on the HPV status of HNSCC has focused primarily on immunologic studies, with limited investigations conducted from a molecular perspective. Our aim for this study is to explore the characteristics of the HPV- and HPV+ xenografts treated with RCT and untreated controls using transcriptomics and epigenomics for outcome correlation for putative stratifying biomarker discovery. Purpose/Objective:

Material/Methods:

In the present work, specimens from the study conducted by Valentini et al. [1] were used. Briefly, xenografts from HPV- (FaDu, SAS, and Cal-33) and HPV+ (UDSCC2, UMSCC47, and UPCISCC154) human HNSCC cell lines were generated. Mice were irradiated with a single 4 Gy dose combined with cisplatin. Untreated mice were included as control group. Samples were taken 24h after treatment, fixed with paraformaldehyde and paraffin embedded (FFPE). In each cell line, three samples were finalized for RNA extractions from both groups, making a total of 36 samples. RNA was extracted from FFPE samples of untreated and treated xenografts and bulk RNA sequencing (RNAseq) was