A Unified Single-Cell Atlas of HNSCC: Uncovering HPV and Sex Variability in the Tumor Microenvironment

Conde-Lopez, C.; Kurth, I.; Hess, J.; Elkabets, M.; Besso, M. J.; Roscher, M.; Hadiwikarta, W. W.; Han, R.; Marripati, D.

doi:10.1101/2025.10.30.685278

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bioRxiv · 10.1101/2025.10.30.685278

A Unified Single-Cell Atlas of HNSCC: Uncovering HPV and Sex Variability in the Tumor Microenvironment

Conde-Lopez, C.·Kurth, I.·Hess, J.·Elkabets, M.·Besso, M. J.·Roscher, M.·Hadiwikarta, W. W.·Han, R.·Marripati, D.

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is highly heterogeneous, with variations driven by HPV status and sex. However, existing single-cell RNA sequencing (scRNA-seq) studies are often limited in sample size and lack standardized methodologies, limiting cross-study comparisons. To address this, we integrated scRNA-seq data from 78 patients (274,911 cells) across multiple studies, creating a unified HNSCC atlas that harmonizes annotations and enables robust tumor microenvironment (TME) analyses. Using STACAS for semi-supervised integration and automated annotation tools such as Ikarus and scGate, we improved tumor and immune cell classification. Leveraging our atlas, we identified HPV- and sex-specific shifts in immune and stromal composition, with HPV+ tumors enriched in adaptive immune cells and HPV- tumors showing more stromal and myeloid populations. Preliminary sex-stratified analyses suggested distinct microenvironmental patterns, warranting further investigation. This publicly available atlas provides a comprehensive framework for reproducibly studying HNSCC biology, improving patient stratification, and may help informing personalized therapies.

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Conde-Lopez, C., Kurth, I., Hess, J., Elkabets, M., Besso, M. J., Roscher, M., Hadiwikarta, W. W., Han, R., Marripati, D.. 2025-10-31. A Unified Single-Cell Atlas of HNSCC: Uncovering HPV and Sex Variability in the Tumor Microenvironment. https://doi.org/10.1101/2025.10.30.685278

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