Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Neoplasms

Uterine Cervical Dysplasia

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Precancerous Conditions

Cervical Intraepithelial Neoplasia

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Vitamins

Proflavine

Acetic Acid

Retinol acetate

Vitamin A

Retinol palmitate

Anti-Bacterial Agents

Adjuvants, Immunologic

Immunologic Factors

Protective Agents

Anti-Infective Agents, Local

Retinol

Visual inspection of cervix performed using 3 - 5% acetic acid to the cervix. Participants undergo standard colposcopy and abnormal lesions noted by quadrant. Then 0.01% proflavine applied topically to the cervix. High-resolution microendoscopy (HRME) then performed. HRME images obtained from one visually normal site and from up to 3 visually abnormal lesions based on visual exam and/or colposcopic findings. Study staff follow up with participant by phone one month after procedure.

0.01% Proflavine applied topically to the cervix after colposcopy and HRME cervical images obtained.

HRME images obtained from one visually normal cervical site, and from up to 3 visually abnormal lesions based on exam and/or colposcopic findings.

HRME Imaging

Study staff follow up with participant by phone one month after procedure.

Phone Call

Colposcopy performed after visual inspection of cervix.

Colposcopy

3 - 5% added to cervix before visual inspection.

Kathleen Schmeler, MD

The goal of this clinical research study is to compare a type of imaging called high-resolution microendoscopy (HRME) for detecting abnormal tissue in the cervix to the standard of care, which is visual inspection with acetic acid (VIA) with a colposcopy procedure. Researchers also want to learn if HRME images can show the difference between cancerous tissue and normal cervical tissue.

If you are found to be eligible to take part in this study, you will first have your scheduled VIA and colposcopy. The study doctor will tell you more about this procedure.

You will then have proflavine hemisulfate solution (contrast dye) applied to your cervix. Images will be collected with the probe from the HRME device. The HRME probe is a long thin tube with a camera at the tip. This should add about 10 minutes to the total procedure time.

The HRME images will be stored in an electronic database and used for research. The images will be deidentified and only the MD Anderson staff will have access. This data will be stored in the database indefinitely (forever).

Any abnormal areas found during the VIA and/or colposcopy will be biopsied as part of your standard of care using very small forceps (a medical tool that is like tongs). If the exam shows no abnormalities, a normal area will be biopsied.

The study doctor will talk to you about the results of the HRME imaging, colposcopy, and biopsy/ies.

There will be no change to the planned standard-of-care colposcopy and biopsy.

Researchers will also collect information from your medical record about the colposcopy, surgery, the status of the disease, and demographics (such as your age).

Follow-Up:

About 1 month after the study procedure, the study staff will contact you by phone to ask how you are doing. The call should last about 5 minutes.

Length of Study:

Your active participation in this study will be over after the biopsy.

This is an investigational study. Proflavine hemisulfate is not FDA approved or commercially available. The HRME device is not FDA approved or commercially available. Both are currently being used for research purposes only.

Up to 800 participants will be enrolled in this study. Up to 400 will take part at MD Anderson and up to 400 will take part at the Harris Health System.

Use of High-Resolution Microendoscopy (HRME) in Patients With Cervical Dysplasia

To evaluate the performance of HRME imaging compared with existing diagnostic techniques including colposcopy and visual inspection with acetic acid (VIA), a successful outcome is defined as concordance between the diagnosis using HRME imaging and the most severe histologic diagnosis. That is, researchers will calculate the concordance with the participant as the experimental unit rather than the biopsy, as each participant may have more than 1 biopsy. Target concordance rate is 70%. Concordance rate monitored using method described by Thall et al. (1995), and trial stopped if concordance rate is less than 70%.

National Cancer Institute (NCI)

National Institutes of Health (NIH)

M.D. Anderson Cancer Center

Infections

Immune System Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Coagulants

Pharmaceutical Solutions

Iodine

Lugol's solution

Cadexomer iodine

Hemostatics

Participants underwent colposcopic exam, followed by Visual Inspection with Lugol's Iodine (VILI) by a second, blinded clinician (the order of exams was reversed to eliminate potential interference with exam results due to iodine staining). Biopsy was done after the VILI.

Participants underwent Visual Inspection with Acetic Acid followed by colposcopy by a second clinician who was blinded to the screening test result.

Visual Inspection with Acetic Acid is the application of acetic acid to a cervix, followed by examination with a light source. It is not a new drug or device, and has been used in resource-limited settings for several decades. The purpose of this trial is to compare the two screening techniques, which had not been done previously.

Visual Inspection with Acetic Acid

Visual Inspection with Lugol's Iodine is the application of lugol's iodine to a woman's cervix, followed by examination with a light source with the goal of detecting precancerous lesions. Like Visual Inspection with Acetic Acid, it is not a new drug or device.

Visual Inspection with Lugol's Iodine

The clinical trial is part of a larger study to evaluate the safety and efficacy of screening techniques for cervical cancer among HIV-infected women. The investigators randomized women to undergo screening with Visual Inspection with Acetic Acid (VIA) or Visual Inspection with Lugol's Iodine (VILI), along with a colposcopy. All outcome and treatment decisions were based on the colposcopy exam done at the study visit. The investigators then compared outcomes between the two groups to assess the test characteristics of both VIA and VILI.

Cervical cancer and HIV are intersecting epidemics that both disproportionately affect low-income women; the impact of the socioeconomic disparity and biologic synergy of these two diseases is seen dramatically in Kenya, where cervical cancer is the most common cancer killer. HIV-infected women are at increased risk for the development of cervical precancer and cancer, develop more aggressive lesions and are affected at younger ages. Although screening for and treatment of precancer has reduced the incidence of cervical cancer to close to zero in resource-rich countries, strategies are costly and not available in most resource-limited countries. Novel testing and treatment methods that can be carried out in low-resource settings are urgently needed to prevent cervical cancer in these settings, especially among HIV-infected women. Using a cross-sectional study design, the investigators tested two potentially low-cost and effective cervical cancer screening methods: visual inspection with acetic acid (VIA) and protein biomarkers expressed in the presence of cervical dysplasia, neither of which have been well-studied in HIV-infected women. Investigators also randomized a small subset of women to undergo VIA compared to Visual Inspection with Lugol's Iodine (VILI) to compare the test characteristics of these two screening exams. In addition, remarkably little is known about the potential impact of the presence, diagnosis and treatment of human papillomavirus-related dysplasia on HIV genital shedding, a major risk factor for HIV transmission. To explore the impact of the presence, diagnosis and treatment of human papillomavirus-related cervical dysplasia on HIV-1 in genital secretions, investigators compared the levels of HIV-1 RNA found in the cervicovaginal secretions of women with no evidence of cervical dysplasia to levels in women with high-grade cervical dysplasia. They also compared the levels of HIV-1 RNA prior to and after cervical biopsy as well as up to 14 weeks after standard treatment for cervical dysplasia using loop electrosurgical excision procedure (LEEP). Results from this study will inform the prioritization and design of safe, effective and low-cost cervical cancer screening and prevention programs for HIV-infected

Visual Inspection With Acetic Acid Compared to Lugol's Iodine in HIV-infected Women

Safety and Validity Evaluation for Cervical Cancer Screening and Treatment Techniques Among HIV-infected Women

Investigators compared the specificity of VIA and VILI for the outcome of cervical intraepithelial neoplasia 2 or greater

Investigators compared the test positivity between VIA and VILI.

Investigators compared the sensitivity of VIA and VILI for the outcome of cervical intraepithelial neoplasia 2 or greater.

Kenya Medical Research Institute

University of California, San Francisco

Symptoms and General Pathology

Communicable Diseases

Papillomavirus Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Disease Attributes

Door-to-door recruitment of women for self-collected HPV testing

Community health meeting recruitment of women for self-collected HPV testing

Self-collection cervical cancer screening, STI screening, and education on HIV by a community health worker. Women who test positive for high-risk HPV types will be referred to a designated health centre for VIA follow-up and treatment if indicated.

Self-collected HPV testing for cervical cancer screening

Gina Ogilvie, MD

Sheona Mitchell-Foster, MD

Carolyn Nakisige, MD

The purpose of this pragmatic cluster randomized control trial is to test the effectiveness of cervical cancer screening follow-up completion using two implementation approaches for self-collected HPV testing in a rural, low-resource setting: 1) community health workers recruiting women door-to-door and 2) community health workers recruiting women at community health meetings.

This study will also help to further understand how current patient referral systems are working between health facilities, patient and provider preferences for integrated care and health system related barriers to integrated cervical cancer screening.

Hypothesis: More women will receive screening via the community health meeting but the engagement to care (i.e., visual inspection with acetic acid-our main outcome) will be greater in the door-to-door arm.

A cluster randomized control trial will be conducted with the objective of understanding differences in the effectiveness of cervical cancer screening models using self-collected HPV testing on engagement in care. In 31 villages, women will be recruited for self-collected cervical cancer and sexually transmitted infection (STI) screening by: 1) Community health worker recruitment for self-collection (door-to-door), 2) community health meetings. Visual inspection with acetic acid (VIA), cryotherapy and thermocoagulation will be offered in local health facilities for all women who test positive for high-risk (HR)-HPV types. Women needing advanced cancer care will be referred to the Uganda Cancer Institute in Kampala.

The unit of randomization (2 arms) will be villages and the analysis will also account for clustering within this unit or randomization. All participants will receive an integrated package of cervical cancer screening and education and will participate in a survey at baseline. Samples will be tested using GeneXpert (XpertHPV) point of care testing at the Kigandalo health facility for HPV and high risk HPV (HR-HPV). Intervention arms will be implemented in phases by year to avoid temporal contamination.

Pragmatic cluster randomized control trial

Integrated Cervical Cancer Screening in Mayuge District Uganda (ASPIRE Mayuge)

Integrated Cervical Cancer Screening in Mayuge District Uganda (ASPIRE Mayuge): A Pragmatic Cluster Randomized Control Trial

Data will be available on request through study investigators.

Measured using years of lives saved compared between each study arm and the ICER

Evaluating reach, fidelity, barriers and facilitators of implementation in each arm from the community and health system perspective using mixed methods

Assess men's knowledge level of HPV and cervical cancer and determine which factors impact the supportiveness towards a partner seeking screening.

Proportion of total screened women who complete VIA follow-up and treatment after testing positive for high-risk HPV type

Total number of women who test positive for HPV out of the total number of samples obtained

Total number of women who test positive for STIs out of total number of women who test positive for HPV; total number of women who test negative for STIs out of total number of women who test positive for HPV; total number of women who test positive for STIs out of total number of women who test negative for HPV; total number of women who test negative for STIs out of total number of women who test negative for HPV

Association (adjusted OR) estimated between HPV and HIV; other STIs

Semi-structured focus group discussions with women who did and did not attend follow-up screening in each study arm.

Mediation analysis using counterfactual approach to assess mediating effect of patient reported experience, knowledge change and co-infection status with other STIs on engagement in care after positive HR-HPV test

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Use of High-Resolution Microendoscopy (HRME) in Patients With Cervical Dysplasia	NCT02420665	Cervical Cancer	Proflavine HRME Imaging Phone Call Colposcopy Acetic Acid	21 Years -	M.D. Anderson Cancer Center
Visual Inspection With Acetic Acid Compared to Lugol's Iodine in HIV-infected Women	NCT02237326	Cervical Intrae... Cervical Cancer HIV	Visual Inspecti... Visual Inspecti...	23 Years - 59 Years	University of California, San Francisco
Integrated Cervical Cancer Screening in Mayuge District Uganda (ASPIRE Mayuge)	NCT04000503	Human Papilloma... Human Papilloma... Papillomavirus ... Cervical Cancer Pre-Cancerous D...	Self-collected ...	25 Years - 49 Years	University of British Columbia

Spots Global Cancer Trial Database for visual inspection with acetic acid