Background/Objectives: Human papillomavirus (HPV) is the main causative agent of cervical cancer and contributes to a significant proportion of other anogenital and oropharyngeal malignancies. The need for better biomarkers and therapeutic approaches in HPV-associated cancers has drawn attention to exosomes, small extracellular vesicles known for their stability, biomolecule transport capabilities, and role in cell-to-cell communication. Methods: This review comprehensively evaluates recent literature on the diagnostic, prognostic, and therapeutic applications of small extracellular vesicles, particularly exosomes, in HPV-related cancers. It analyzes findings on exosomal nucleic acids, proteins, and long non-coding RNAs, as well as engineered exosome-based therapies. Results: Exosomal miRNAs (e.g., miR-204-5p, miR-99a-5p, miR-21), proteins (e.g., glycolytic enzymes, HSP90), and lncRNAs (e.g., HOTAIR, DLEU1) have emerged as promising biomarkers for disease detection and monitoring. Exosomal cargo actively participates in HPV-related tumor progression. For example, miRNAs such as miR-21 and miR-146a modulate immune cell polarization and inflammatory signaling, while lncRNAs like HOTAIR promote oncogenic transcriptional programs. Exosomal proteins including HSP90 and ANXA1 facilitate extracellular matrix remodeling and immune evasion, thereby influencing tumor growth and metastasis. In HPV-positive head and neck and cervical cancers, exosomal cargo reflects HPV status, tumor progression, and treatment response. Therapeutic studies demonstrate the utility of exosomes in vaccine delivery, immune modulation, and drug delivery systems, including the use of PROTACs. However, clinical translation faces barriers including isolation protocol standardization, biomarker validation, and scalable production. Conclusions: Exosomes hold great promise for integration into diagnostic and therapeutic workflows for HPV-related cancers. Future research should focus on resolving standardization issues, validating biomarkers in diverse cohorts, and optimizing engineered exosome platforms for targeted therapy.
背景/目的：人乳头瘤病毒（HPV）是宫颈癌的主要致病因子，并在其他肛门生殖器和口咽部恶性肿瘤中占据显著比例。对HPV相关癌症中更优生物标志物和治疗策略的需求，使外泌体这一小型细胞外囊泡受到关注。外泌体以其稳定性、生物分子运输能力及在细胞间通讯中的作用而著称。方法：本综述全面评估了近期关于小型细胞外囊泡（尤其是外泌体）在HPV相关癌症中诊断、预后和治疗应用的文献。分析了外泌体核酸、蛋白质、长链非编码RNA以及工程化外泌体疗法的相关发现。结果：外泌体miRNA（如miR-204-5p、miR-99a-5p、miR-21）、蛋白质（如糖酵解酶、HSP90）和lncRNA（如HOTAIR、DLEU1）已成为疾病检测和监测中极具前景的生物标志物。外泌体内容物积极参与HPV相关肿瘤进展。例如，miR-21和miR-146a等miRNA可调节免疫细胞极化和炎症信号传导，而HOTAIR等lncRNA则促进致癌转录程序。包括HSP90和ANXA1在内的外泌体蛋白促进细胞外基质重塑和免疫逃逸，从而影响肿瘤生长和转移。在HPV阳性头颈癌和宫颈癌中，外泌体内容物反映了HPV状态、肿瘤进展和治疗反应。治疗研究表明，外泌体在疫苗递送、免疫调节和药物递送系统（包括PROTACs的应用）中具有重要价值。然而，临床转化面临诸多障碍，包括分离方案标准化、生物标志物验证和规模化生产等。结论：外泌体在整合到HPV相关癌症的诊断和治疗流程中具有巨大潜力。未来研究应聚焦于解决标准化问题、在不同队列中验证生物标志物，并优化用于靶向治疗的工程化外泌体平台。
Exosomes in HPV-Associated Cancers: From Biomarkers to Engineered Therapeutics
肿瘤(癌症)患者之家