Liquid Biopsy for Minimal Residual Disease Assessment in Endometrial and Cervical Cancers: Molecular Rationale, Clinical Evidence, and Translational Barriers

Endometrial and cervical cancers can recur from subclinical disease not evident on routine surveillance. This narrative review critically evaluates liquid biopsy for minimal residual disease (MRD) assessment and recurrence monitoring. Post-treatment human papillomavirus (HPV) circulating tumor DNA (ctDNA) in cervical cancer has the strongest disease-specific prospective evidence of clinical validity; persistent detection is strongly associated with recurrence, but moderate sensitivity and false-negative results do not support treatment de-escalation on negativity alone. With regard to endometrial cancer, perioperative ctDNA has prognostic support from an 11-study, 1298-patient meta-analysis and additional cohorts, although assay heterogeneity and limited independent replication constrain clinical readiness. Postoperative positivity generally shows stronger associations than preoperative detection. Cervicovaginal and urine DNA-methylation studies provide preliminary evidence for detecting established recurrence, especially local recurrence, but not prospective molecular lead time or clinical utility. Digital PCR, disease-specific fixed panels, tumor-informed assays, and error-corrected sequencing serve distinct settings; broad pan-cancer plasma profiling remains mainly an advanced-disease tool. Circulating tumor cells, extracellular vesicles, microRNAs, tumor-educated platelets, and fragmentomics remain exploratory. Liquid biopsy should remain an investigational adjunct until prospective trials show that acting on molecular findings improves outcomes.