{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:39:54Z","timestamp":1792431594835,"version":"4.5.0"},"reference-count":100,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers17203386","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:24:02Z","timestamp":1761056642000},"page":"3386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Exosomes in HPV-Associated Cancers: From Biomarkers to Engineered Therapeutics"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9544-8830","authenticated-orcid":false,"given":"Muharrem Okan","family":"Cakir","sequence":"first","affiliation":[{"name":"School of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6370-8683","authenticated-orcid":false,"given":"Melis","family":"Selek","sequence":"additional","affiliation":[{"name":"School of Medicine, Koc University, Sar\u0131yer, Istanbul 34450, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-0284","authenticated-orcid":false,"given":"Betul","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine & Genetic and Metabolic Disease Research and Investigation Center, Marmara University, Istanbul 34854, Turkey"},{"name":"Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize 53100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Ozdogan","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Memorial Hospital, Antalya 07050, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-5111","authenticated-orcid":false,"given":"G. Hossein","family":"Ashrafi","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","unstructured":"(2025, July 05). Centers for Disease Control and Prevention Cancers Caused by HPV, Available online: https:\/\/www.cdc.gov\/hpv\/about\/cancers-caused-by-hpv.html."},{"key":"ref_2","unstructured":"(2025, July 07). World Health Organization Cervical Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cervical-cancer."},{"key":"ref_3","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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