A Single-Cell Transcriptome Atlas of Epithelial Subpopulations in HPV-Positive and HPV-Negative Head and Neck Cancers
Year: 2026
Type: article
Abstract: Persistent infection with HPV causes nearly 5% of all cancers worldwide, including cervical and oropharyngeal cancers. Compared to HPV-negative (HPV−) head and neck squamous cell carcinomas (HNSCCs), HPV-positive (HPV+) HNSCCs exhibit a significantly improved treatment response; however, established treatment regimens were largely developed for HPV− disease. Effectively de-escalating therapy and optimizing treatment protocols to minimize toxicity for both HPV+ and HPV− tumors has been variably successful, in part due to the heterogeneity of cellular subpopulations. Single-cell RNA sequencing (scRNAseq) has primarily been used to define immune cell populations rather than the cell type of origin, epithelial cells. To address this, we analyzed published scRNAseq data of HPV+ and HPV− HNSCCs to distinguish epithelial tumor cell populations as a function of HPV status. We identified the transcriptome signatures, ontologies, and candidate biomarkers of newly identified epithelial subpopulations with attention to those that are shared or enriched in HPV+ or HPV− HNSCCs. We hypothesize that distinct epithelial cell populations and reprogramming in HPV− versus HPV+ HNSCC represent important components of the pro-tumor environment. These are described here as a foundation for the identification of new epithelial-cell-specific biomarkers, effectors, and candidate targets for optimizing the treatment of HNSCC.
Source: UNC Libraries
DOI: 10.17615/n4nq-z889
Institution: University of North Carolina at Chapel Hill
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Top Sector Agri and Food, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Naito Foundation, Uehara Memorial Foundation, Wellcome Trust, Cerebral Palsy Alliance Research Foundation, Hydrocephalus Association, SRM Institute of Science and Technology, Ministry of Education - Singapore, National Natural Science Foundation of China, Grantová Agentura České Republiky, Technische Universiteit Eindhoven, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Research Foundation of Korea, Animal and Plant Quarantine Agency, Department of Finance of Jilin Province, Washington University School of Medicine in St. Louis, Japan Society for the Promotion of Science, National Institute of Mental Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, Core Research for Evolutional Science and Technology, Argonne National Laboratory
OpenAlex ID: W7203910808
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