Liquid Biopsy in Cervical Cancer: Hopes and Pitfalls.

Abstract

Simple SummaryCervical cancer is the fourth most common cancer in women worldwide, and its incidence is variably distributed between developed and less-resourced countries, in which socio-economic issues and religious beliefs often limit the widespread diffusion and the access to screening campaigns. In the “liquid biopsy” era, the application of non-invasive and repeatable techniques to the identification of diagnostic, prognostic, and predictive biomarkers might facilitate the management of this disease and, hopefully, improve its outcome. The purpose of this review is to explore the progress status of liquid biopsy in cervical cancer patients. Several methods are described, which include the analysis of circulating tumor cells, the search for pathogenic mutations on circulating tumor DNA, as well as the identification of circulating RNAs, focusing on their potential clinical applications and current limitations.Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main cause of CC, as well as in the access and quality of services for CC prevention and diagnosis. At present, the most diffused screening and diagnostic tools for CC are Papanicolaou test and the more sensitive HPV-DNA test, even if both methods require gynecological practices whose acceptance relies on the woman’s cultural and religious background. An alternative (or complimentary) tool for CC screening, diagnosis, and follow-up might be represented by liquid biopsy. Here, we summarize the main methodologies developed in this context, including circulating tumor cell detection and isolation, cell tumor DNA sequencing, coding and non-coding RNA detection, and exosomal miRNA identification. Moreover, the pros and cons of each method are discussed, and their potential applications in diagnosis and prognosis of CC, as well as their role in treatment monitoring, are explored. In conclusion, it is evident that despite many advances obtained in this field, further effort is needed to validate and standardize the proposed methodologies before any clinical use.