Leveraging Methylated DNA Markers (MDMs) in the Detection of Endometrial Cancer, Ovarian Cancer, and Cervical Cancer

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.

Inclusion Criteria for Cohort 1:

Patients will be ≥45 years of age and meet one of the following criteria:

• Abnormal uterine bleeding
• Postmenopausal bleeding

OR

Patients ages 18 - 44 years of age and meet these criteria

• Abnormal uterine bleeding
• One risk factor for endometrial cancer (BMI ≥30 or PCOS or Tamoxifen use)

Exclusion Criteria for Cohort 1:

• 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
• Chemotherapy within the past 5 years
• Current biopsy-proven cervical, vaginal, or vulvar cancer or lower genital tract dysplasia
• Current biopsy-proven endometrial cancer or endometrial hyperplasia
• Current biopsy-proven benign endometrial polyp
• Endometrial biopsy/sampling within the preceding 1 month showing benign endometrium

Inclusion Criteria for Cohort 2:

Patients will be ≥18 years of age and meet at least one of the following criteria:

• Presence of biopsy-proven EC (any histology, including uterine carcinosarcoma) and surgical intervention planned. Surgical intervention can include any of the following: hysterectomy, D\&C, hysteroscopic resection
• Biopsy showing AEH or EIN with surgical intervention planned. Surgical intervention can include any of the following: hysterectomy, D\&C, hysteroscopic resection, etc)

Exclusion Criteria for Cohort 2:

• Undergoing surgical procedure for recurrent or metastatic EC
• Received preoperative neoadjuvant chemotherapy or radiotherapy for current EC diagnosis
• Prior hysterectomy
• Current known pregnancy diagnosis
• Prior or current biopsy-proven cervical cancer
• Presence of concomitant biopsy-proven cervical dysplasia
• Any prior pelvic or vaginal radiotherapy
• Any prior cancer (except basal cell skin cancer) within the past 5 years
• Chemotherapy within the past 5 years
• Prior intervention or surgery with intent to completely remove the target pathology

Inclusion Criteria for Cohort 3:

Patients will be ≥18 years of age, have a cervix and meet at least one of the following criteria:

• History of current abnormal cervical/endocervical Pap test for which the patient is presenting for colposcopy
• Cervical mass identified on physical exam and patient referred for cervical biopsy, even if colposcopy not recommended or indicated
• Planned clinically indicated surgical excisional biopsy or removal of the cervix (cold knife cone, LEEP, hysterectomy) for abnormal Pap test, cervical dysplasia, cervical mass, or biopsy-proven invasive cervical cancer (adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, or less common primary cervical carcinomas all eligible)

Exclusion Criteria for Cohort 3:

• History of pelvic or vaginal radiotherapy
• Prior total hysterectomy (cervix removed) for any indication
• Current known pregnancy diagnosis
• Cervical mass biopsy-proven to be EC or a cancer metastatic from a non-cervical origin
• Any prior cancer (except basal cell skin cancer) within the past 5 years
• Chemotherapy within the past 5 years
• Patients presenting for colposcopy as part of lower genital tract dysplasia or cancer surveillance after prior curative intent treatment and no current Pap abnormality or cervical mass
• Prior intervention or surgery with intent to completely remove the target pathology for the current lesion / diagnosis during the current episode

Inclusion Criteria for Cohort 4:

Patients will be ≥45 years of age and should meet at least one of the following criteria:

• Undergoing hysterectomy with biopsy-proven or clinically presumed (based on imaging and/or clinical symptoms) benign gynecologic or uterine pathology of fibroids, endometriosis, adenomyosis, or benign endometrial polyps.
• Undergoing any gynecologic surgery in which a benign pathologic tissue diagnosis of fibroids, endometriosis, adenomyosis, or benign endometrial polyp is anticipated to be confirmed.

Exclusion Criteria for Cohort 4:

• Endometrial biopsy or office hysteroscopy within 2 weeks preceding the planned gynecologic surgery procedure for fibroids, endometriosis, benign endometrial polyps, or adenomyosis
• Any surgery within the past 3 months
• Prior hysterectomy
• Current known pregnancy diagnosis
• Prior or current biopsy-proven gynecologic cancer
• Current biopsy-proven AEH/EIN, cervical, vaginal, or vulvar dysplasia
• Prior pelvic or vaginal radiotherapy
• Any prior cancer (except basal cell skin cancer) within the past 5 years
• Chemotherapy within the past 5 years
• Undergoing hysterectomy for prolapse without a coexisting known or presumed benign uterine pathologic diagnosis of fibroids, endometriosis, benign endometrial polyps, or adenomyosis
• Prior intervention or surgery with intent to completely remove the target pathology for the current lesion / diagnosis during the current episode

Inclusion Criteria for Cohort 5:

Patients with a uterus will be ≥45 years of age and should meet the following criteria:

• Presenting for GYN wellness exam, ± Pap test
• No change in medical conditions, new diagnoses, or new medications within the past 6 months

Exclusion Criteria for Cohort 5:

• Pap test or cervical biopsy within the past 1 month
• Endometrial biopsy or office hysteroscopy within the past 1 month
• Any surgery within the past 3 months
• Prior hysterectomy
• Current known pregnancy diagnosis
• Prior or current biopsy-proven gynecologic cancer
• Current biopsy-proven AEH/EIN, cervical, vaginal, or vulvar dysplasia
• Prior pelvic or vaginal radiotherapy
• Any prior cancer (except basal cell skin cancer) within the past 5 years
• Chemotherapy within the past 5 years
• Criteria met for inclusion in any of the other study cohorts

Inclusion Criteria for Cohort 6:

Patients ≥50 years of age and:

• Postmenopausal
• At least 1 intact ovary
• Diagnosis of an adnexal mass or a clinical suspicion of early-stage ovarian cancer (including fallopian tube cancer)
• Planned surgery for the adnexal mass
• For vaginal fluid collection, patient must have a uterus, cervix and at least 1 intact fallopian tube* (without prior tubal ligation/occlusion)

Exclusion criteria for Cohort 6:

• Any current or prior cancer diagnosis (except basal cell or squamous cell skin cancer, non-gyn)
• Chemotherapy for cancer treatment within the past 5 years prior to collection
• Clinically suspected advanced stage ovarian cancer (Stage III or IV) on presentation, if known prior to specimen collection
• Surgical candidates for recurrent ovarian cancer
• History of pelvic or vaginal radiation therapy
• Known current synchronous endometrial cancer or hyperplasia
• Known current cervical, vaginal, or vulvar dysplasia

Inclusion criteria for Cohort 7:

Women will be ≥18 years of age and meet the following criteria:

• Presence of clinically probable ovarian, fallopian tube, or primary peritoneal cancer (all under the umbrella of OC) based on clinical findings of any/all of the following: imaging showing adnexal and/or abdominal masses consistent with probable ovarian cancer, omental caking, elevated CA125, ascites, imaging-guided biopsy consistent with OC pathology
• Newly diagnosed with ovarian, fallopian tube or primary peritoneal cancer without neoadjuvant therapy
• At least one intact ovary
• For vaginal fluid collection, patient must have a uterus, cervix and at least 1 intact fallopian tube* (without prior tubal ligation/occlusion)

Exclusion criteria for Cohort 7:

• Patients with recurrent OC
• Any current or prior cancer diagnosis (except basal cell or squamous cell skin cancer, non-gyn) within the past 5 years
• Chemotherapy for cancer treatment within the past 5 years prior to collection
• History of pelvic or vaginal radiation therapy
• Known current synchronous endometrial cancer or hyperplasia
• Known current cervical, vaginal, or vulvar dysplasia
• Current known pregnancy diagnosis