The diagnostic and prognostic potential of extracellular vesicles as biomarkers for thyroid cancer: a systematic review.

The incidence of thyroid cancer, the most common endocrine malignancy, has increased by 313% in the past four decades and is now the seventh most common cancer worldwide. There is an urgent need for non-invasive diagnostic, prognostic, and surveillance biomarkers to improve patient outcomes. Given the promising role of extracellular vesicles (EVs) as liquid biopsy biomarkers, a systematic review of the literature was conducted to evaluate their diagnostic and prognostic utility in thyroid cancer. We also assessed the quality of included studies giving special emphasis to methodology, reporting standards, and adherence to MISEV2018 guidelines. A comprehensive search was conducted across Web of Science, Ovid Medline, Ovid Embase, Scopus, and Emcare for English-language studies published from inception to March 2025. Search terms included a combination of relevant keywords and subject Headings. A total of 40 studies met the inclusion criteria. Most focused on papillary thyroid carcinoma, with relatively a minority investigating follicular thyroid carcinoma. The majority examined small EVs (exosomes), with microRNAs (miRNAs) being the most studied EV biomarkers, followed by proteins, circular RNAs, long non-coding RNAs, mRNAs, DNA, procoagulant phospholipids, and biophysical characteristics. No studies investigated EV lipids or metabolites as potential thyroid cancer biomarkers. This systematic review highlights the strong potential of EVs as diagnostic and prognostic biomarkers in thyroid cancer. However, larger prospective patient cohorts are needed to validate current findings. Clinical translation will require standardised methodologies and robust comprehensive reporting aligned with MISEV2018 guidelines, enhancing reproducibility and paving the way for multicentre clinical trials.