Comprehensive circulating tumor DNA mutation profiling via CAPP-Seq liquid biopsy for cervical cancer.

Abstract

Background: Liquid biopsy using circulating tumor DNA (ctDNA) is a minimally invasive approach for detecting tumor-associated genomic alterations. Although ctDNA analysis has been widely explored in solid tumors, its application to cervical cancer remains limited. Cancer personalized profiling by deep sequencing (CAPP-Seq) enables sensitive ctDNA profiling via molecular barcoding and digital error suppression.

Methods: We evaluated the feasibility of ctDNA-based mutation profiling in cervical cancer using the CAPP-Seq platform by analyzing plasma samples from 38 patients.

Results: The cohort included three patients with stage I disease, nine with stage II, 19 with stage III, and seven with stage IV. Somatic gene alterations were detected in 33 of the 38 cases (87%), including squamous cell carcinoma (27/29 [93%]) and adenocarcinoma (6/9 [67%]). Non-synonymous mutations were identified in 23 patients (59%), with PIK3CA being the most frequently mutated gene [13/38 (34%)]. Copy number gains of EGFR, MET, and ERBB2 were observed in 24%, 11%, and 5% of cases, respectively. The median blood tumor mutational burden was 17.7 mutations/Mb, and 50% of the patients exhibited a hypermutated phenotype. In a subset of four patients who received concurrent chemoradiotherapy, longitudinal changes in ctDNA mutation profiles between pre- and post-treatment samples were associated with treatment response.

Conclusions: This study demonstrates the feasibility of ctDNA-based mutation profiling using CAPP-Seq in cervical cancer, with a high detection rate of tumor-associated genomic alterations across histological subtypes. ctDNA analysis may represent a minimally invasive approach for the molecular characterization and disease monitoring of cervical cancer.