Genomic Profiling in Patients with Endometrial Cancer by Deep Sequencing of Vaginal Swabs and Plasma.

PURPOSE: Endometrial cancer is a common gynecologic malignancy that lacks effective noninvasive screening tools as traditional approaches rely on invasive biopsies. In this large prospective study, we evaluated a novel approach combining vaginal swab DNA and plasma-based ctDNA for genomic profiling to provide a comprehensive framework for diagnosis, prognosis, and disease monitoring.

EXPERIMENTAL

DESIGN

Adult patients with diverse stages of endometrial cancer, preneoplastic disease, and benign endometrial conditions were prospectively recruited over 2 years. Paired vaginal swab DNA and plasma-based ctDNA were collected preoperatively, and additional plasma samples were obtained at multiple time points postoperatively. Deep next-generation sequencing targeting 101 genes was performed, achieving an average depth exceeding 40,000×.

RESULTS

A total of 191 patients contributed 388 samples. Vaginal swab DNA demonstrated 77.7% sensitivity and 96.6% specificity. PTEN mutations were associated with favorable prognosis (HR: 0.27; 95% confidence interval, 0.092-0.77), and TP53 mutations were associated with poor prognosis (HR: 3.7; 95% confidence interval, 1.4-10). A novel classification system based on the mutational profile of PTEN/TP53 identified distinct prognostic groups. Plasma-based ctDNA was significantly associated with stage, lymphovascular invasion, and prognosis (P < 0.01 for all). Patients with preoperative positive plasma-based ctDNA results exhibited poorer outcomes (P < 0.01), whereas postoperative positive ctDNA results enabled early detection of recurrence.

CONCLUSIONS

These two noninvasive methods play distinct, complementary roles in the management of endometrial cancer. Vaginal swab DNA and novel PTEN/TP53-based classification have distinct prognostic advantages over existing frameworks. Plasma-based ctDNA provides dynamic insights into recurrence risk and disease progression.