Work

Single-cell transcriptomic profiling reveals distinct tumor microenvironments in HPV-associated penile squamous cell carcinoma

Year: 2025

Type: article

Abstract: 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: 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.

Source: Precision Clinical Medicine

DOI: 10.1093/pcmedi/pbaf013