Human Papilloma Virus (HPV) Circulating Tumor DNA (ctDNA) in Cervical Cancer
Human Papilloma Virus (HPV) Circulating Tumor DNA (ctDNA) in Cervical Cancer
This study collects blood samples to determine if the DNA of HPV that causes cervical cancer
 can be detected in patients with cervical cancer that is new (primary), has come back
 (recurrent), or has spread to other places in the body (metastatic) and are undergoing
 treatment with surgery, radiotherapy, chemotherapy, and/or immunotherapy. Researchers may use
 this information to predict response (good or bad) of the cervical cancer to treatment and
 detect recurrent cancer sooner.
PRIMARY OBJECTIVES:

 I. To estimate the ctDNA detection rate in cervix cancer patients undergoing surgery,
 radiotherapy, chemotherapy, and/or immunotherapy in the setting of primary, recurrent or
 metastatic disease.

 II. Association of ctDNA baseline levels and clearance kinetics with clinical and
 radiographic tumor response.

 III. To explore the association of detectable ctDNA at each time point with invasive
 recurrence-free survival and overall survival.

 IV. To explore the use of ctDNA for surveillance and detection of disease recurrence.

 V. To create a repository for future exploratory studies including analyzing changes in T
 cell and other immune cell subpopulations during and following therapy for cervix cancer.

 OUTLINE: Patients are assigned to 1 of 4 cohorts.

 COHORT 1: Patients undergo collection of blood samples at baseline prior to surgery, at 6
 weeks, 3, 6, and 12 months post-surgery, every 6 months during year 2, and at the time of
 recurrence (if applicable).

 COHORT 2: Patients undergo collection of blood samples at baseline prior to the first
 fraction of radiation, during week 4 of radiotherapy, at 6 weeks, 3, 6, and 12 months
 post-radiotherapy, every 6 months during year 2, and at the time of recurrence (if
 applicable).

 COHORT 3: Patients undergo collection of blood samples at baseline prior to the first
 fraction of radiation, during week 4 of radiotherapy, on the day of the final fraction of
 radiotherapy, at 3 months post-radiotherapy, every 3 months during years 1 and 2, and at the
 time of recurrence (if applicable).

 COHORT 4: Patients undergo collection of blood samples at baseline prior to initiation of
 chemotherapy or immunotherapy, at 4 weeks and 8 weeks after initiation of chemotherapy or
 immunotherapy, every 3 months during years 1 and 2, and at the time of recurrence (if
 applicable).
Inclusion Criteria:

 -  Able to provide written consent

 -  Patient has given permission to give tumor/blood sample for research testing

 -  Histological confirmation of squamous cell carcinoma or adenosquamous carcinoma

 -  Known HPV status defined as positive staining for p16 on immunohistochemistry (IHC) or
 DNA in situ hybridization (ISH) for HPV

 -  Willingness to return to enrolling institution for follow-up (during the Active
 Monitoring Phase of the study)

 -  Consent to allow blood specimens to be shared with potential external collaborators

 -  Cohort #1: Surgery alone for early stage disease (Federation of Gynecology and
 Obstetrics [FIGO] stage IA-IB1)

 -  FIGO 2019 stage IA1, IA2, IB1

 -  Plan to undergo surgery including but not limited to trachelectomy, radical
 hysterectomy, and lymph node dissection

 -  Cohort #2: Post-operative radiation +/- chemotherapy for intermediate and high risk
 factors

 -  Any FIGO stage

 -  Status post any definitive surgical procedure (e.g. radical hysterectomy and
 lymph node dissection) and on final pathology found to have risk factors:

 -  Intermediate risk: Lymphovascular space invasion (LVSI), deep cervical
 stromal invasion, tumor size > 4 cm

 -  High risk: pelvic or para-aortic lymph nodes, parametrial invasion, positive
 surgical margins

 -  Plan to undergo pelvic +/- para-aortic radiotherapy with or without chemotherapy
 per standard of care

 -  Cohort #3: Definitive chemoradiotherapy for locally advanced disease (FIGO stage
 IB2-IIIC)

 -  FIGO 2019 Stage IB2-IIIC or not a surgical candidate

 -  Plan to undergo definitive chemoradiotherapy including external beam
 radiotherapy, brachytherapy, and chemotherapy

 -  Cohort #4: Systemic treatment for recurrent or metastatic disease

 -  Any recurrence (local, regional, or distant) after prior treatment for cervical
 cancer

 -  Metastases at first diagnosis without prior treatment

 Exclusion Criteria:

 -  Other active malignancy =< 2 years prior to registration.

 -  EXCEPTIONS: Non-melanotic skin cancer

 -  NOTE: If there is a history or prior malignancy, they must not be receiving other
 specific treatment for cancer

 -  Pregnancy or lactation

 -  Inability on the part of the patient to understand the informed consent to be
 compliant with the protocol