ESTRO 2026 - Abstract Book PART I

S1452

Interdisciplinary - Other

ESTRO 2026

based guidelines in cancer care. J Natl Compr Canc Netw. 2013;11(1):114–121. Keywords: Multidisciplinary Tumor Boards, LMIC

Subsequent quality control and literature-based selection led to a five-gene cancer-testis (CT) panel (RIBC2, TCAM1P, SMC1B, STAG3, SYCP2)3. This panel was applied to stratify HPV-positive patients treated with radiotherapy (RT, TCGA cohort, n = 50) and with postoperative cisplatin-based radiochemotherapy (RCT, DKTK adjuvant cohort, n = 87) using k-means clustering and survival analysis. Functional enrichment analyses were conducted to elucidate biological differences between CT expression-defined subgroups. Results: Integration of preclinical and clinical datasets revealed coordinated transcriptional and epigenetic regulation of six HPV-associated genes, with five displaying testis- specific expression and forming the refined CT panel. Application of this panel stratified HPV-positive patients into molecularly and prognostically distinct groups. In the TCGA RT cohort, high CT expression was associated with significantly improved overall (p = 0.042), progression-free (p = 0.033), and disease- specific survival (p = 0.042). In the DKTK RCT adjuvant cohort, three distinct CT expression clusters (low, intermediate, and high) were observed; low CT expression identified patients with the poorest outcomes, particularly among p16-positive cases (p = 0.021). Functional analyses indicated enrichment of epithelial-to-mesenchymal transition and TP53 pathway disruption in low-CT tumors, whereas high-CT tumors exhibited active DNA repair signaling and intact p53 function, indicating a potential link between CT expression and tumor radiosensitivity.

Poster Discussion 3769

Cancer-Testis gene panel identifies high and low- risk HPV-positive HNSCC patients treated with postoperative radiochemotherapy Safayat Mahmud Khan 1,2 , Julian Schlecker 1,3 , Rosemarie Euler-Lange 1,2 , Sona Michliková 4,5 , Cylia Ouadah 4,5 , Verena Bitto 1 , Wahyu W. Hadiwikarta 1,3 , Chiara Valentini 4 , Annett Linge 4,6 , Steffen Loeck 5,6 , Mechthild Krause 4,6 , Michael Baumann 1,3 , María J. Besso 1,3 , Ina Kurth 1,3 1 Radiooncology/ Radiobiology, DKFZ, Heidelberg, Germany. 2 National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany. 3 German Cancer Consortium (DKTK), Core Center Heidelberg, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 4 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 5 OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, HZDR, Dresden, Germany. 6 German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Dresden, Germany Purpose/Objective: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) generally demonstrates favorable outcomes, yet a subset of patients experiences poor prognosis1,2. Current clinical markers are insufficient to differentiate low- risk patients eligible for treatment de-escalation from high-risk individuals who may require more intensive therapy. This study aimed to establish a molecular stratification approach capable of identifying biologically and prognostically distinct subgroups within HPV-positive HNSCC, thereby enabling more personalized treatment strategies beyond conventional clinical staging. Material/Methods: We performed an integrated multi-omics analysis of treatment-naïve specimens, incorporating transcriptomic (RNA-seq) and epigenomic (DNA methylation array) data from both preclinical xenograft models (three HPV-positive and three HPV- negative cell lines; biological replicates, n = 18) and the TCGA-HNSC cohort (n = 487). Differential gene expression and methylation analyses were carried out to identify HPV-associated candidate genes.

Figure 1:Schematic model (Created with BioRender.com) Conclusion:

This five-gene cancer-testis panel enables robust molecular stratification of HPV-positive HNSCC into prognostically relevant risk groups. High CT expression

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