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

Inclusion Criteria for Cohort 1:

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

• Abnormal uterine bleeding

• Postmenopausal bleeding

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:

Women 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

• Receipt of 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:

Women 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

Inclusion Criteria for Cohort 4:

Women 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

Inclusion Criteria for Cohort 5:

Women will be ≥45 years of age and should meet the following criteria:

• Presenting for well-woman 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:

Women ≥50 years of age and:

• Postmenopausal status

• 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 tampon collection, patient must have a uterus, cervix and at least 1 intact fallopian tube* (without prior tubal ligation/occlusion)

Exclusion criteria - Isolated Adnexal Mass cohort: (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 - OC Cohort: (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 tampon collection, patient must have a uterus, cervix and at least 1 intact fallopian tube* (without prior tubal ligation/occlusion)

Exclusion criteria - OC Cohort (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