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Updated: Jan 18, 2026
RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
Single-cell transcriptomic profiling reveals distinct tumor microenvironments in HPV-associated penile squamous cell
Lianbang Zhu1,2, Deyun Shen1, Jiahao Zhou3
1Department of Urology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, China.
Background:
Penile squamous cell carcinoma (PSCC) is a rare yet potentially lethal malignancy, often resulting in devastating disfigurement, with a 5-year survival rate of only ∼50%. Human papillomavirus (HPV) infection is implicated in approximately half of PSCC cases and is associated with improved clinical outcomes; however, the underlying mechanisms remain poorly understood.
Methods:
To elucidate HPV-associated differences in the tumor microenvironment, we performed single-cell RNA sequencing on tumors from 11 treatment-naïve PSCC patients, analyzing a total of 52 980 single cells. Unsupervised clustering identified 49 distinct cellular clusters across immune and stromal compartments.
Results:
HPV-positive tumors exhibited an increased abundance of mast cells and a reduction in the proliferative macrophages subpopulation compared to HPV-negative tumors. Notably, CD8+ T cells in HPV-positive PSCC expressed lower levels of immune checkpoint molecules, suggesting a less exhausted immune state. Conversely, TIGIT and its ligands were significantly enriched in HPV-negative tumors, potentially fostering an immunosuppressive niche.
Conclusion:
Collectively, our study delineates the single-cell landscape of PSCC and highlights distinct tumor microenvironment remodeling associated with HPV status, suggesting that the reduced immunosuppression in HPV-positive tumors may underlie their more favorable prognosis.
