The following is a summary of “Detection of endometrial cancer using tampon-based collection and methylated DNA markers,” published in the July 2023 issue of Gynecologic Oncology by Bakkum-Gamez et al.

Alterations in DNA methylation are early events in the development of endometrial cancer (EC) and may help detect EC via tampon-collected vaginal fluid. To discover differentially methylated regions (DMRs), DNA from frozen EC, benign endometrium (BE), and benign cervicovaginal (BCV) tissues underwent reduced representation bisulfite sequencing (RRBS). The selection of candidate DMRs was based on receiver operating characteristic (ROC) discrimination, methylation level fold-change between malignancies and controls, and absence of background CpG methylation. qMSP validated methylated DNA markers (MDM) on DNA extracted from independent EC and BE FFPE tissue sets. 

Before clinically indicated endometrial sampling or hysterectomy, women ≥45 years old with abnormal uterine bleeding (AUB) or postmenopausal bleeding (PMB) or any age with biopsy-proven EC self-collected vaginal fluid using a tampon—qMSP analysis of vaginal fluid DNA for EC-associated MDMs. A random forest modeling analysis was conducted to generate the predictive probability of the underlying disease; the results were cross-validated 500-fold in-silico. About 33 MDM candidates met tissue performance criteria. For the tampon pilot, 100 EC cases were frequently matched to 92 BE controls based on menopausal status and tampon collection date. A 28-MDM panel distinguished between EC and BE with high discriminatory power (96% (95%CI 89–99%) specificity; 76% (66–84%) sensitivity (AUC 0.88). 

In PBS/EDTA tampon buffer, the panel demonstrated a specificity of 96% (95% CI: 87–99%) and a sensitivity of 82% (70–91%) (AUC = 0.91). The sequencing of the methylome of the next generation, stringent filtration criteria, and independent validation yielded exceptional MDM candidates for EC. EC-associated MDMs demonstrated promisingly high sensitivity and specificity in tampon-collected vaginal fluid; adding EDTA to a PBS-based tampon buffer enhanced sensitivity. There is a need for more extensive EC MDM testing studies involving tampons.

Source: sciencedirect.com/science/article/pii/S0090825823001853