Proteomic Profiling of Exosomes from HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma: Selective Cargo Packaging

Oncogenic viruses, such as human papillomavirus (HPV), alter the endosomal system to manipulate the proteomic content of extracellular vesicles, aiding their persistence and disease progression. HPV has emerged as a key risk factor for head and neck squamous cell carcinoma (HNSCC). However, the influence of HPV on the exosomal proteomics remains poorly understood. Label-free quantitative proteomics was employed to analyze proteins extracted from HPV16-positive (93VU147T, UDSCC2) and HPV-negative (OCT1) HNSCC cell lines and their exosomes. Data are available via ProteomeXchange with identifier PXD067001. PCA revealed distinct clustering of HPV16-positive and -negative cells and exosomes. Differential expression analysis revealed 130 and 136 DEPs in exosomes of 93VU147T and UDSCC2, respectively, and 326 and 320 DEPs in the corresponding cells. Gene Ontology enrichment showed that HPV16-positive exosomal proteins and cells were associated mainly with protein digestion and absorption, different neurodegenerative diseases, and PI3K/Akt signaling. Exosomes showed distinct profiling from that of parental cells, emphasizing selective cargo packaging. Overall, the study demonstrates that HPV modulates the exosomal content in HNSCC, suggesting potential implications in tumor progression and biomarker discovery.