From squamous intraepithelial lesions to cervical cancer: Circulating microRNAs as potential biomarkers in cervical carcinogenesis.

Despite the essential role of Human Papillomavirus (HPV) in cervical carcinogenesis, other factors are required for cancer establishment, like miRNAs. Such molecules present a complex biogenesis, being diversely distributed across tissues and biological fluids, as cell-free miRNAs or miRNAs present in extracellular vesicles (EV). After HPV infection, an interplay between HPV and the miRNA network occurs in cervical cells. As the virus persists and cellular transformation occurs, specific patterns of miRNA expression are found in different stages of cervical disease. Thus, defining promising miRNAs/specific miRNA signatures - especially circulating miRNAs - represents an interesting strategy for screening (diagnosis, prognosis, etc.) those stages. Despite the limited number of studies investigating circulating miRNAs in distinct biological fluids, accumulating data have pointed to some promising candidates, both as cell-free or EV-derived miRNAs. Here we highlight some of these promising non-invasive biomarkers and bring attention to the urgent need for efforts in this field.