Extracellular Vesicles as Emerging Cervical Cancer Diagnostic and Molecular Signatures of Tumor and Immune Dynamics

Cervical cancer remains a major worldwide health concern and ranks as the fourth most common malignancy affecting women, especially in low- and middle-income countries, where early screening and monitoring facilities are limited. Though several screening strategies, including Pap smears, colposcopy, computed tomography, and HPV testing, are available for the detection of cervical carcinoma, these methods cope with various challenges, such as diagnostic errors, false-positive and false-negative results, invasiveness, and sample collections, which could lead to unnecessary anxiety and procedures. Recent studies suggest that extracellular vesicles (EVs) are emerging as a promising noninvasive diagnostic and prognostic tool for early detection of cervical cancer. EVs are secreted by almost all types of cells, including tumor cells, into various biofluids and carry molecular signatures reflective of their cells of origin. EVs exhibit stability in circulation due to their protective lipid bilayer and are enriched with nucleic acids, proteins, and lipids that serve as potential biomarkers. Particularly, tumor-derived EVs from tissues, plasma, urine, and vaginal secretions have demonstrated diagnostic value in cervical cancer by carrying oncogenic miRNAs, lncRNAs, miR-221-3p, and proteins such as DLX6-AS1 and survivin. Furthermore, EVs contribute to cancer by immune modulation, metastasis, and treatment resistance, underscoring EVs' diagnostic and prognostic potential. Compared to conventional liquid biopsies, EVs provide enhanced biomarker stability and specificity. This review highlights the biogenesis, isolation methods, functional role, and clinical significance of EVs, and their integration into cervical cancer screening and management strategies.