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Profiling the Tumor Immune Microenvironment of HPV-Associated Base of Tongue Squamous Cell Carcinoma

Year: 2025
Type: article
Abstract: Reham M Alahmadi,1,* Maaweya Awadalla,2,* Najat Marraiki,1 Mohammed Alswayyed,3 Hajar A Alshehri,2 Amjad Alsahli,2 Hatim A Khoja,4 Osamah T Khojah,5,6 Rawan M Alahmadi,7 Nada Farid,6 Bandar Alosaimi2 1Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Research Labs, Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh, Saudi Arabia; 3Department of Pathology and Laboratory Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 5Pathology Department, Hematology Unit, King Saud University, & Dr. Suliman Al-Habib Medical Group, Riyadh, Saudi Arabia; 6Dr. Suliman Al-Habib Medical Group, Riyadh, Saudi Arabia; 7Head and Neck Surgery Division, Department of Otolaryngology/Head and Neck Surgery, Prince Sultan Military Medical City, Riyadh, Saudi Arabia*These authors contributed equally to this workCorrespondence: Bandar Alosaimi, Email [email protected]: Base of tongue squamous cell carcinoma (BOTSCC) is a prevalent and aggressive form of oral cancer, often associated with poor patient outcomes. The tumor microenvironment (TME) of HPV-positive BOTSCC is critical in influencing cancer progression and treatment response.Objective: This study aims to analyze the TME of HPV-positive BOTSCC by examining the expression of key genes involved in various biological processes.Methods: We utilized the RT2 Profiler PCR Array to quantify the expression of 168 genes related to inflammation, immunity, oncogenesis, tumor suppression, apoptosis, and angiogenesis. Enrichment analysis of cancer hallmarks was performed on all upregulated genes. Additionally, we investigated the correlation between the expression levels of the ten most highly upregulated genes and survival prognosis in HPV-associated BOTSCC patients.Results: Our analysis revealed dysregulation of 42 genes associated with tumor-immune interactions, with 20 genes upregulated and 22 downregulated. Furthermore, we identified 64 genes linked to cancer development, with 33 upregulated and 31 downregulated. High-risk HPV (hr-HPV) genotypes were found in 81% of patients, predominantly HPV-35 and HPV-16.Conclusion: This study highlights the complexity of the HPV-positive BOTSCC TME, underscoring the need for further research into molecular pathways and immune interactions to identify new therapeutic targets for improved cancer treatment.Plain Language Summary: Base of tongue squamous cell carcinoma (BOTSCC) is a highly aggressive form of oral cancer often associated with poor prognosis. This study focuses on the tumor microenvironment (TME) in HPV-positive BOTSCC, investigating the expression of 168 genes implicated in anti-inflammatory, anti-tumor, and other critical biological functions. Among these, 64 genes associated with cancer growth and regulation and 42 genes involved in tumor-immune interactions were identified as dysregulated. The high-risk HPV-35 strain emerged as the most prevalent subtype. Further analysis explored the impact of the most significantly upregulated genes on immune cell dynamics within the tumor and patient survival outcomes. These findings provide novel insights into the complex TME of HPV-positive BOTSCC, underscoring the importance of further research to delineate key molecular pathways and identify potential therapeutic targets. Keywords: HPV, base of tongue squamous cell carcinoma, gene expression, tumor microenvironment, inflammation, oncogenes, tumor suppressor gene, immunity crosstalk
Authors: Alahmadi,Reham, Awadalla,Maaweya, Marraiki,Najat, Alswayyed,Mohammed, Alshehri,Hajar, Alsahli,Amjad, Khoja,Hatim, Khojah,Osamah, Alahmadi,Rawan, Farid,Nada, Alosaimi,Bandar
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W7052259888
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