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oai:figshare.com:article/32641686 2026-10-01T16:21:13Z portal_1172 item_type_8 month_year_10_2026

Impact of immune status and clinical outcomes in oropharyngeal cancer Mohammad Maddallah Faleh Albraikat (24170163) PUREID: 655438680 Oropharyngeal squamous cell carcinoma (OPSCC) human papillomavirus tumour-infiltrating lymphocytes stromal TILs digital pathology computational Pathology RNA-sequencing prognostic biomarkers Gene Expression Profiling immunohistochemistry systemic immune biomarkers peripheral blood biomarkers HPV-positive vs HPV-negative OPSCC personalized medicine Background: Oropharyngeal squamous cell carcinoma (OPSCC) is a biologically and clinically heterogeneous disease, known for having distinct molecular and prognostic features primarily driven by smoking, alcohol and human papillomavirus (HPV) infection. The immune system has emerged as a critical factor influencing cancer prognosis and survival. However, reliable, scalable, and interpretable approaches for defining the immune status of OPSCC patients and their impact in routine diagnostic settings remain limited. <br><br>Objectives: This thesis aims to comprehensively evaluate the prognostic and biological significance of OPSCC immune status through an integrative, multimodal approach: (1) to develop, evaluate and validate a tumour-infiltrating lymphocyte (TIL) classification in OPSCC, with attention to HPV-related differences and the prognostic significance of stromal TILs (STC%) in survival; (2) to identify enriched gene signatures from bulk RNA exome capture sequencing (ecRNA-seq) and validate these at the protein level via digital IHC analysis, considering associations with HPV, STC% and outcomes; (3) to explore systemic immunity using pre-treatment blood-based biomarkers, assessing links with outcomes, HPV status, and tumour TILs. <br><br>Methods: In Chapter 2, a hand-crafted algorithm was developed to classify STC% in digital H&E slides (WSIs and TMAs) and applied to a Northern Irish OPSCC cohort, with external validation. STC% was analysed in relation to survival, independent of HPV. Chapter 3 used ecRNA-seq to profile tumours stratified by STC% and HPV. Enriched gene signatures linked to prognosis were validated by IHC (CD3, CD8, CD20) on matched TMAs. Chapter 4 analysed systemic immune biomarkers from blood counts in a later NI OPSCC cohort, evaluating prognostic impact and correlation with STC%. <br><br>Key Findings: The digital TIL algorithm showed prognostic value, with STC-high tumours independently associated with improved survival in both HPV+ and HPV− OPSCC. Transcriptomic profiling of STC-high cases revealed enrichment of B and T cell-related signatures linked to prognosis, validated by IHC. Systemic immune biomarkers also predicted outcomes and showed a modest correlation with STC%. <br><br>Conclusion: This thesis presents a novel digital pathology algorithm for semi-automated quantification of stromal TILs, integrating transcriptomics, IHC and systemic biomarkers to reveal immune subclasses of OPSCC with prognostic significance, independent of HPV status. <br><br>Thesis is embargoed until 31 July 2028.<br> 2026-10-01T16:21:13Z Text Thesis 10.17034/32641686.v1 https://figshare.com/articles/thesis/Impact_of_immune_status_and_clinical_outcomes_in_oropharyngeal_cancer/32641686 All Rights Reserved Open Access after 2028-07-31