Mobile High-Resolution Microendoscopy (mHRME) for the Detection of Cervical Dysplasia in El Salvador

Completed

• Conditions: Cervical Cancer
• Interventions: Diagnostic Test: HRME

• Registration Number: NCT04472455
• Lead Sponsor: William Marsh Rice University

Brief Summary

Evaluate the performance of the mHRME in a study of 3,000 women in San Salvador to assess whether mHRME imaging improves specificity of screening by VIA or HPV DNA without reducing sensitivity for cervical precancer and cancer.

Detailed Description

This is a prospective cohort study. Eligibility is open to women 30-49 years old, who are not pregnant, have an intact cervix, and no history of cervical cancer.

Visit 1:

Patients will enroll at the screening clinic of the Instituto del Cáncer de El Salvador (El Salvador Cancer Institute, ICES). An informed consent will be obtained. They will be given a urine pregnancy test; if negative, two cervical samples will be collected. The first sample will be used to screen for HPV DNA. New technologies to screen for oncoproteins and HPV will be applied to the second sample. 3-5% acetic acid will also be applied to the cervix to perform the VIA. Images of the cervix will be taken and any personally identifiable information removed.

Visit 2:

All women with a positive VIA or HPV test will undergo additional evaluation. In addition, 10% of women in the double negative group (VIA-/HPV-) will be randomly selected for evaluation. This evaluation includes: Urine pregnancy test, VIA, colposcopy, Lugol's solution application, and a HRME. 3-5% acetic acid will be applied to the cervix to perform the VIA. Proflavine and Lugol's solution (2-5%) will be applied and once again the health care provider will record their impression for each of the abnormal lesions. Cervical images will be taken. Then, 0.01% proflavine will be topically applied to the cervix for 1 minute. Images will be obtained using the mHRME system of a visually normal site and then of all lesions identified by VIA, colposcopy, and/or Lugol's solution. If no lesions are identified by VIA, colposcopy, and/or Lugol's solution, mHRME images will be taken of each quadrant. Samples of abnormal areas identified by VIA, colposcopy, Lugol's solution, and/or mHRME will be collected for biopsy and ECC purposes. If the evaluation shows no abnormalities, a random sample will be collected from the squamocolumnar junction and an ECC will be performed (only if the patient is HPV positive). Two expert pathologists will review and classify the samples. All research results will be unbeknownst to them. They will use the following classification system: normal, CIN 1, CIN 2, CIN 3, AIS, or cancer, per standard criteria. Discrepant results are resolved by a third expert pathologist, with the final result being based on 2/3 agreement. If all three pathologists arrive at different diagnoses, all three will meet in person to review to reach a consensus diagnosis. Women with CIN 2+ will undergo an excision or cryotherapy, according to the treatment standard. Patients diagnosed with invasive cancer will be referred to gynecology/oncology.

The sensitivity, specificity, positive predictive value, and negative predictive value for each screening and triage method will be compared using histopathology as the gold standard. These results will enable us to compare the total number of women that could have received adequate and inadequate treatment based on five of the most predominant clinical scenarios: VIA alone, VIA/mHRME triage, HPV test alone, HPV/VIA triage, and HPV/mHRME triage.

Study Timeline

• Study Start: 2015-09
• Primary Completion: 2019-04-02
• Study Completion: 2019-04-02
• Status Verified: 2020-06
• Study First Submitted: 2020-07-10
• Study First Submitted QC: 2020-07-10
• Last Update Submitted: 2020-07-10
• Study First Posted: 2020-07-15
• Last Update Posted: 2020-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 1827

Inclusion Criteria

1. Women who are between the ages of 30 and 49 years of age
2. All women must have a negative urine or serum pregnancy test prior to any study procedure (within 7 days)
3. Intact cervix (patients who have undergone previous LEEP, cone and/ or cryotherapy are not eligible)
4. No history of invasive cervical cancer
5. Able and willing to provide informed consent

Exclusion Criteria

1. Women < 30 years of age or over 49 years of age
2. Women who have undergone a hysterectomy with removal of the cervix
3. Women who have had a previous LEEP, Cold knife cone and/or cryotherapy
4. Women who are pregnant or breastfeeding
5. Women with a history of invasive cervical cancer
6. Unable or unwilling to provide informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
10% Of Screen Negative Group	HRME	10% of women who screened negative at Visit 1 and were invited to Visit 2
Screen Negative Group	HRME	All women who screen negative at Visit 1.
Screen Positive Group	HRME	All women who screened positive at Visit 1 and were invited to Visit 2

Primary Outcome Measures

Name	Time	Method
Accuracy of mHRME to detect CIN2+	1-2 days	Calculate the sensitivity, specificity, positive predictive value, and negative predictive value of mHRME to detect CIN2+.

Secondary Outcome Measures

Name	Time	Method
Comparison of different screening and triage strategies to detect CIN2+	1-2 days	Compare the sensitivities and specificities of the following theoretical strategies to detect CIN2+: VIA alone, VIA/mHRME triage, HPV test alone, HPV/VIA triage, and HPV/mHRME triage.