Liquid biopsy in gynecologic cancers: Cellular origin to early detection and precision care

Gynecological cancers, encompassing malignancies of the cervix, vagina, uterus, fallopian tubes, and ovaries, remain a significant global health burden despite advances in cancer therapeutics and epidemiological trends. According to the International Agency for Research on Cancer (IARC), these neoplasms account for approximately 19% of nearly 5 million new cancer cases and 3 million deaths annually, disproportionately impacting women in low- and middle-income countries. Traditional diagnostic approaches, including histological tumor biopsies, play a critical role in cancer classification and molecular characterization; however, such invasive procedures pose limitations related to patient suitability, procedural risks, and sampling biases due to tumor heterogeneity. This scenario highlights the urgent need for innovative, minimally invasive diagnostic modalities capable of early detection and personalized disease management. Liquid biopsy has emerged as a promising noninvasive alternative, harnessing circulating tumor-derived biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), tumor-educated platelets (TEPs), extracellular vesicles (EVs), and circulating RNAs. Since the first identification of ctDNA in female-specific malignancies in 2012, there have been substantial technological advances over the past decade that underscore the clinical potential of liquid biopsies in gynecological oncology. These circulating biomarkers provide dynamic insights into tumor genetics and heterogeneity, facilitating early diagnosis, prognostication, and real-time monitoring while circumventing the limitations of tissue biopsies. This review highlights current evidence on liquid biopsy applications for gynecological cancers, focusing on recent methodological progress, biomarker validation, and diagnostic utility. Furthermore, it addresses existing challenges related to sensitivity, specificity, and standardization, emphasizing the translational prospects of liquid biopsy in enhancing personalized management and improving clinical outcomes for women afflicted with gynecological malignancies.