The overarching objective of this project is to develop a pan-gynecologic cancer detection test using gynecologic (unique endometrial, cervical, and ovarian cancer) cancer-specific methylated DNA markers and high-risk human papilloma virus (HR-HPV) detected in vaginal fluid and/or plasma.
This proposal defines Phase II MDM-based cancer detection studies in endometrial cancer (EC) and endometrial hyperplasia with atypia (AEH) in vaginal fluid and 2) ovarian cancer (OC) in plasma and vaginal fluid. Additionally, it defines necessary Phase I MDM-based cancer detection and exploratory aims to test novel cervical cancer (CC) MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.er detection and exploratory aims to test novel cervical cancer MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.
Abnormal uterine bleeding
Postmenopausal bleeding
Abnormal uterine bleeding
One risk factor for endometrial cancer (BMI ≥30 or PCOS or Tamoxifen use)
Prior hysterectomy
Current known pregnancy diagnosis
Any prior pelvic or vaginal radiotherapy
Any prior cancer (except basal cell skin cancer) within the past 5 years
Patients presenting to a GYN or GYN Surgery Clinic for evaluation of symptoms or for consultation and planned procedures as outlined in the seven study cohort descriptions.
Cohort
Prospective
Vaginal Fluid Collection
Diagnostic testA sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.
Blood Collection
Diagnostic testA blood sample will be collected from each participant prior to undergoing any exams or procedures.
7
Treatment groupsSee each treatment group below.
Develop predictive models from a panel of EC-specific MDMs and validate their performance in identifying underlying EC and AEH within vaginal fluid in a larger, more diverse cohort.
Complete a phase II biomarker development study of a methylated DNA marker (MDM)-based endometrial cancer detection test performed on vaginal fluid. The phase II aspect of this biomarker development study will narrow the number of endometrial cancer MDMs within the biomarker panel in order to optimize the next phase of test development.
Develop predictive models from a panel of OC-specific MDMs and validate their performance in identifying underlying OC within vaginal fluid and plasma in a larger, more diverse cohort.
Complete a phase II biomarker development study of a methylated DNA marker (MDM)-based ovarian cancer detection test performed on vaginal fluid. The phase II aspect of this biomarker development study will narrow the number of ovarian cancer MDMs within the biomarker panel in order to optimize the next phase of test development.
Using 95% specificity cutoffs of the final MDM EC panel, determine the false positive rate among women undergoing surgical removal of common benign gynecologic pathology
As part of this biomarker test development, understanding whether common non-cancerous uterine or gynecologic conditions may also lead to the finding of currently apparent endometrial cancer-specific MDMs in vaginal fluid is critical in determining specificity, positive predictive value, and negative predictive value of the test.
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