Bedard Mary C, Rivera-Cruz Cosette M, Chihanga Tafadzwa, VonHandorf Andrew, Tang Alice L, Zender Chad, Weirauch Matthew T, Ferris Robert, Wise-Draper Trisha M, Adam Mike, Wells Susanne I
Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Viruses. 2025 Mar 24;17(4):461. doi: 10.3390/v17040461.
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.
人乳头瘤病毒（HPV）的持续感染导致全球近5%的癌症，包括宫颈癌和口咽癌。与HPV阴性（HPV-）头颈部鳞状细胞癌（HNSCC）相比，HPV阳性（HPV+）HNSCC的治疗反应显著改善；然而，既定的治疗方案主要是针对HPV阴性疾病制定的。有效降低治疗强度并优化治疗方案以尽量减少HPV+和HPV-肿瘤的毒性，其成效不一，部分原因是细胞亚群的异质性。单细胞RNA测序（scRNAseq）主要用于定义免疫细胞群体，而非起源细胞类型（上皮细胞）。为解决这一问题，我们分析了已发表的HPV+和HPV- HNSCC的scRNAseq数据，以根据HPV状态区分上皮肿瘤细胞群体。我们确定了新鉴定的上皮亚群的转录组特征、本体和候选生物标志物，并关注那些在HPV+或HPV- HNSCC中共享或富集的特征、本体和标志物。我们假设，HPV-与HPV+ HNSCC中不同的上皮细胞群体和重编程代表了促肿瘤环境的重要组成部分。在此将其作为鉴定新的上皮细胞特异性生物标志物、效应物和候选靶点的基础，以优化HNSCC的治疗。
