ArticleClinical and experimental otorhinolaryngology2026
Human Papillomavirus (HPV)-Infected Epithelial Cells and FBLN1-Positive Fibroreticular Cells Govern the Immunogenic Tumor Microenvironment in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.
Article in Clinical and experimental otorhinolaryngology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesOropharyngeal squamous cell carcinoma (OPSCC) exhibits distinct clinical behaviors according to human papillomavirus (HPV) status. HPV-associated OPSCC is typically associated with a more favorable prognosis and improved response to therapy than non-HPV-associated OPSCC; however, the underlying differences in the tumor microenvironment (TME) remain incompletely understood.
methodsTo investigate cellular and molecular factors associated with improved outcomes in HPV-associated OPSCC, we performed single-cell RNA sequencing and high-resolution spatial transcriptomics on samples from two non-HPV-associated OPSCCs, five HPV-associated OPSCCs, and three normal tonsils, with a particular focus on fibroreticular cells (FRCs).
resultsFour distinct FRC subsets were identified, with FBLN1-positive FRCs significantly enriched in HPV-associated OPSCC. These cells expressed SLIT2, a molecule implicated in immune cell recruitment. Spatial mapping demonstrated that FBLN1-positive FRCs were closely associated with both tumor and immune cells, suggesting a role in promoting an immunogenic TME. In addition, HPV-associated OPSCC exhibited higher levels of proliferating epithelial cells and increased expression of antigen-presentation genes than non-HPV-associated tumors.
conclusionThese findings highlight the potential role of FBLN1-positive FRCs in promoting immune activation within the TME of HPV-associated OPSCC. Enhanced antigen presentation and epithelial proliferation may facilitate tumor-immune interactions, potentially contributing to improved clinical outcomes. This study advances understanding of TME dynamics in OPSCC and may inform future therapeutic strategies.
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