Brief Title
HRME: Screening for Cervical Cancer and Its Precursors in Low-Resource Settings
Official Title
Point-of-Care, Real-Time Optical Imaging to Enable Screening for Cervical Cancer and Its Precursors in Low-Resource Settings
Brief Summary
A new mobile diagnostic and treatment unit is being developed by BCH to address the loss-to
follow-up associated with the mobile screening program and demonstrate POC diagnosis by HRME.
The mobile diagnostic and treatment unit will be equipped with the tools and infrastructure
necessary to perform HRME, VIA, colposcopy, biopsy and treatment with cryotherapy. A team of
a colposcopist, nurse, nursing assistant, and driver will staff the mobile diagnostic and
treatment unit. The unit will travel to offer follow-up diagnostic and treatment services to
women who have screened positive during a prior visit with the mobile screening unit. The
mobile diagnostic and treatment unit will be constructed and maintained at BCH.
Detailed Description
A new mobile diagnostic and treatment unit is being developed by BCH to address the loss-to
follow-up associated with the mobile screening program and demonstrate POC diagnosis by HRME.
The mobile diagnostic and treatment unit will be equipped with the tools and infrastructure
necessary to perform HRME, VIA, colposcopy, biopsy and treatment with cryotherapy. A team of
a colposcopist, nurse, nursing assistant, and driver will staff the mobile diagnostic and
treatment unit. The unit will travel to offer follow-up diagnostic and treatment services to
women who have screened positive during a prior visit with the mobile screening unit. The
mobile diagnostic and treatment unit will be constructed and maintained at BCH.
The study will include 200 women with abnormal Pap tests identified through BCH's existing
mobile screening program. Participants will be randomized by cluster to receive follow up
care either through the new mobile diagnostic and treatment unit (experimental arm) or
through recall to BCH (standard of care). We are using cluster randomization to avoid
contamination between arms because some women getting mobile unit services may be concerned
that they are getting lesser services than what they could get at BCH or some women being
referred to BCH may resent not having the convenience of a mobile unit. Because the areas
visited by the mobile units are geographically isolated, we do not anticipate any patients
crossing over to the other study arm.
VIA will be performed with 5% acetic acid applied to the cervix and any abnormal lesions
noted. Standard colposcopy will then be performed and abnormal lesions noted. Proflavine
(0.01%) will then be applied topically. Lugol's solution will then be applied and colposcopy
performed and abnormal lesions noted. Proflavine (0.01% will then be reapplied. HRME images
will be acquired from any areas that are abnormal by VIA and/or colposcopy. In addition, all
4 quadrants will be probed by HRME (4Q HRME) to ensure that non-acetowhite lesions are also
located. The provider will note their impression of the lesion and the HRME image at each
site (normal, benign, low-grade precancer, high grade precancer or cancer). The entire HRME
imaging procedure should add less than 10 minutes to the standard colposcopy exam. VIA,
colposcopy and HRME observations will recorded by quadrant. Any abnormal areas by VIA and/or
colposcopy will be biopsied. If no abnormal areas are noted, one cervical biopsy will be
obtained from a normal appearing area with a HRME image of this area obtained. Two expert
pathologists, blinded to all study results, will review histology and classify as either
normal, CIN1, CIN2, CIN3, AIS or cancer, according to standard criteria; discrepant results
will be resolved by consensus review.
TREATMENT:
Women randomized to the mobile diagnostic and treatment unit who have a HSIL Pap and/or a
lesion noted by VIA and/or colposcopy will undergo immediate treatment with cryotherapy
following biopsies, provided the lesion meets the following criteria: 1) covers <75% of the
ectocervix; 2) can be fully covered with the cryotherapy tip; 3) does not extend into the
endocervical canal. If the colposcopic findings are concerning for invasive cancer or the
lesion is not amenable to treatment with cryotherapy, the patient will be referred
immediately to BCH for additional evaluation and treatment per standard of care.
Women with a biopsy showing CIN2+ who did not undergo cryotherapy due to a negative
VIA/colposcopy, will be recalled to BCH immediately for LEEP (CIN2/3). Women with a biopsy
showing CIN2/3 who underwent cryotherapy will be recalled to BCH or the mobile unit for a
6-month follow-up visit. If persistent or recurrent disease is noted, they will be referred
to BCH for further treatment. Women with a biopsy showing cancer of adenocarcinoma in situ
(AIS) will be recalled to BCH immediately for cold knife cone (CKC) or other evaluation and
treatment per standard of care regardless of whether or not cryotherapy was performed. Women
with CIN1 or less will return for follow-up to the mobile unit or BCH for follow-up at 12
months. Women randomized to return to a central facility for follow up care will undergo VIA,
colposcopy, HRME and biopsies as described above. Patients found to have CIN2+ will be
treated per standard of care at BCH.
Study Type
Interventional
Primary Outcome
Treatment completion rate.
Secondary Outcome
Efficacy (ability to detect CIN 2+ in women with previous abnormal Pap test).
Condition
Neoplasia of the Uterine Cervix
Intervention
High-Resolution Microendoscopy Imaging
Study Arms / Comparison Groups
HRME - Prevention Mobile Unit
Description: Procedures to be done in the mobile unit (van): Visual inspection will be performed with 5% acetic acid (VIA) applied to the cervix followed by standard colposcopy. Proflavine (0.01%) will then be applied topically. Lugol's solution will then be applied and colposcopy performed and abnormal lesions noted. HRME images will be acquired from any areas that are abnormal by VIA and/or colposcopy. VIA, colposcopy and HRME observations will recorded by quadrant. Any abnormal areas by VIA and/or colposcopy will be biopsied. If no abnormal areas are noted, one cervical biopsy will be obtained from a normal appearing area with a HRME image of this area obtained.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Device
Estimated Enrollment
200
Start Date
September 1, 2015
Completion Date
December 31, 2016
Primary Completion Date
August 31, 2016
Eligibility Criteria
Inclusion Criteria:
1. Women with an abnormal Pap test (atypical squamous cells of undetermined significance
or more severe interpretations [≥ASC-US])
2. Women with an intact cervix (patients who have undergone previous LEEP, cone and/or
cryotherapy are eligible)
3. Women of childbearing potential must have a negative urine or serum pregnancy test
4. Women who are at least 18 years of age or older
5. Ability to understand and the willingness to provide informed consent and sign a
written Informed Consent Document (ICD)
Exclusion Criteria:
1. Women <18 years of age
2. Women who have undergone a hysterectomy with removal of the cervix
3. Women with a known allergy to proflavine or acriflavine
4. Women who are pregnant or nursing
5. Women unable or unwilling to provide informed consent or sign a written Informed
Consent Document (ICD)
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
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Administrative Informations
NCT ID
NCT02494310
Organization ID
HRME-UH2
Responsible Party
Principal Investigator
Study Sponsor
Barretos Cancer Hospital
Collaborators
William Marsh Rice University
Study Sponsor
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Verification Date
February 2017