- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03931083
Screening Test Accuracy of Gynocular™, HR-HPV Testing, VIA for Detection of Cervical Neoplastic Lesions, in Women Living With HIV
October 30, 2020 updated by: University of Bern
Screening Test Accuracy of a Gynocular™, HR-HPV Testing, and VIA for Detection of Cervical Intraepithelial Neoplasia, Grade Two and Above, in Women Living With HIV in Lusaka, Zambia
Cervical cancer in HIV-positive women is largely preventable through regular screening.
The World Health Organization (WHO) recommends cervical screening for HIV-positive women every three years.
Currently the least costly method for screening and the most viable option for many countries is visual inspection after application of acetic acid (VIA).
Alternative testing methods are HPV testing and assessment with a portable magnification device.
The investigators plan to assess and compare the screening test accuracy of these screening tests in women living with HIV.
All women will receive histopathology reference standard.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
Detailed Description
The simplest and least costly method for cervical cancer screening is visual inspection after application of acetic acid (VIA).
However, the ability of this screening method to correctly identify precancerous lesions (sensitivity) and women free from these lesions (specificity) is limited.
The investigators aim to identify alternative screening methods which maximize sensitivity and specificity, particularly in HIV-infected women in receiving care in Southern Africa.
The investigators will evaluate the screening test accuracy of a new portable magnification device , the Gynocular™ with Swede score assessment, in women who are HIV-positive and eligible for cervical cancer screening.
The investigators will assess the accuracy of the device when used as a stand alone test, as well as when used subsequent to positive VIA or HPV tests.
The investigators will make comparisons with current screening practices (VIA alone), as well as, recommended screening practices (HPV testing).
The investigators will enrol 450 HIV-positive women receiving care for HIV/AIDS at the Centre for Infectious Disease Research in Zambia, in Lusaka, Zambia.
Consenting women will be screened with VIA, HPV testing and visual assessment with Gynocular™.
All women undergo biopsy (reference standard) and receive treatment as indicated and in accordance with national guidelines.
Study Type
Observational
Enrollment (Anticipated)
450
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Katayoun Taghavi, MD
- Phone Number: +41 31 631 35 23
- Email: katayoun.taghavi@ispm.unibe.ch
Study Contact Backup
- Name: Albert Manasyan, MD
- Email: Albert.Manasyan@cidrz.org
Study Locations
-
-
-
Lusaka, Zambia
- Recruiting
- Centre for Infectious Disease Research in Zambia
-
Contact:
- Albert Manasyan, MD
- Email: Albert.Manasyan@cidrz.org
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Sampling Method
Non-Probability Sample
Study Population
The study population includes women who are enrolled in the ART program at Kanyama Clinic, Lusaka, Zambia.
Kanyama Clinic is situated on the western side of the central business district, 3km away from the town centre.
It has a catchment population of 262,715.
It has registered 52,658 people living with HIV, of which 40,650 have commenced treatment.
In addition to ART services, the clinic has also been providing cervical cancer screening since October 2006.
The clinic is well established in the application of cancer screening based on a "screen-and-treat" approach, where women undergo visual screening, followed by immediate treatment where possible.
Since inception in 2006, the clinic has screened over 23,900 women for cervical cancer.
Clinic nurses are trained to offer cervical cancer screening and treatment with cryotherapy or thermal coagulation and to refer suspicious cases for LEEP and further treatment.
Description
Inclusion Criteria:
- HIV-infected women confirmed through medical records
- Women residing within Lusaka district and plans to stay in this area for the next 6 months
- Women between 18 and 65 years of age (age bracket as per Zambian guidelines for cervical cancer screening)
- Able and willing to consent
- Willing to undergo a pelvic examination and cancer screening
- Has had sexual intercourse before
- Agrees to have follow-up appointment in 6 months
Exclusion Criteria:
- Women with a history of cervical cancer or previous hysterectomy (where the cervix was also removed)
- Pregnant women or women who plan to get pregnant within the next 6 months
- Women who have been vaccinated against HR-HPV
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Portable magnification device (Gynocular™)
The Gynocular™ examination will be performed following the steps involved in colposcopy as described in the IARC colposcopy manual.
These steps include: visualization of the vagina, vulva and cervix following insertion of a speculum, magnified assessment after application of normal saline, examination of cervical vessel patterns using the red-free mode (or green filter), application of 5% acetic acid for 1 minute and finally assessment following application with Lugol's iodine.
The findings of the live examination will be documented using the parameters of the Swede score.
Each parameter is scored between zero and two.
Treatment will be based on the results found at histopathology, unless the woman is also VIA positive in which case, after biopsy she will undergo routine treatment as per local guidelines.
The results will be used to determine the optimal threshold for treatment in WLHIV.
|
The investigators will compare three different screening methods: visual assessment with portable magnification device , visual inspection after application of acetic acid, screening for high risk variants of HPV.
All patients will receive cervical biopsies and histopathological examination.
|
Testing for high risk HPV (HRHPV)
To reduce the number of examinations undergone by the study participant during the same day, HRHPV testing will be carried out at the time of the first gynecological examination by the VIA nurse (see next arm).
Using specific single-use cervical cytobrush provided by GeneXpert, a specimen will be collected immediately prior to VIA examination.
Cervical cytobrush specimens will be placed into ThinPrep PreservCyt (Cepheid, Sunnyvale, CA) immediately after collection.
The HR-HPV testing of cervical specimens will be conducted by a GeneXpert™ machine (Cepheid, Sunnyvale, CA), which will be placed at the health facility and will be operated by a trained nurse in accordance with the manufacturer's instructions.
Additionally, as part of the baseline clinical characteristics of the study participant, the study participant will undergo an STI test at the same time.
The sample will be collected and tested using the same GeneXpertTM platform.
|
The investigators will compare three different screening methods: visual assessment with portable magnification device , visual inspection after application of acetic acid, screening for high risk variants of HPV.
All patients will receive cervical biopsies and histopathological examination.
|
Visual inspection with acetic acid (VIA)
VIA, which is standard of care for cervical cancer screening in Zambia, will be carried out using the methodology described by IARC.
This is summarized as follows: visualization of the vagina, vulva and cervix following insertion of a speculum; assessment with the naked eye after application of normal saline; and further assessment after application of 5% acetic acid for 1 minute.
This will be recorded as normal or abnormal by the assessor.
|
The investigators will compare three different screening methods: visual assessment with portable magnification device , visual inspection after application of acetic acid, screening for high risk variants of HPV.
All patients will receive cervical biopsies and histopathological examination.
|
Histopathological examination of tissue biopsies
All acetowhite lesions will be biopsied.
When no lesion is seen, one biopsy is taken from each quadrant at the squamocolumnar junction.
Biopsies will be sent and examined in a South African based lab.
All histological slides will also be verified independently by an IARC trained pathologist at the end of the study.
Histological endpoints are defined by the CIN classification system: CIN 1 affects only the lower third of the epithelium (mild dysplasia), CIN 2 involves two thirds of the epithelium and CIN 3 involves the full thickness (severe dysplasia and carcinoma in situ).
These findings can be dichotomized by the Lower Anogenital Squamous Terminology into low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL).
All patients with CIN grade 2 that stained diffusely positive for p16 are considered as HSIL, all patients with CIN 3 are considered as HSIL.
Expression of p16 will be visually assessed by immunohistochemistry.
|
The investigators will compare three different screening methods: visual assessment with portable magnification device , visual inspection after application of acetic acid, screening for high risk variants of HPV.
All patients will receive cervical biopsies and histopathological examination.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Test accuracy (sensitivity, specificity) of the Gynocular™ when used as stand-alone tests to detect CIN2+
Time Frame: 6 months
|
To estimate the sensitivity and specificity of the Gynocular when used as a standalone tests to detect CIN2+ among WLHIV.
|
6 months
|
Test accuracy (sensitivity, specificity) of HR-HPV when used as stand-alone tests to detect CIN2+
Time Frame: 6 months
|
To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+ among WLHIV.
|
6 months
|
Test accuracy (sensitivity, specificity) of VIA when used as stand-alone tests to detect CIN2+
Time Frame: 6 months
|
To estimate the sensitivity and specificity of VIA when used as a standalone tests to detect CIN2+ among WLHIV.
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diagnostic test accuracy of the Gynocular™to detect CIN2+/HSIL: other estimates, stand alone
Time Frame: 6 months
|
To determine other estimates of test accuracy of the Gynocular™ (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).
|
6 months
|
Diagnostic test accuracy of HR-HPV testing to detect CIN2+/HSIL: other estimates, stand alone
Time Frame: 6 months
|
To determine other estimates of HR-HPV testing test accuracy (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).
|
6 months
|
Diagnostic test accuracy of VIA to detect CIN2+/HSIL: other estimates, stand alone
Time Frame: 6 months
|
To determine other estimates of VIA test accuracy (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).
|
6 months
|
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination
Time Frame: 6 months
|
To determine estimates of test accuracy for combinations of screening tests, i.e.
HR-HPV followed by Gynocular™
|
6 months
|
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination
Time Frame: 6 months
|
To determine estimates of test accuracy for combinations of screening tests, i.e.
Gynocular™ followed by HR-HPV
|
6 months
|
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination subgroup analyses
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination
Time Frame: 6 months
|
To determine estimates of test accuracy for combinations of screening tests, i.e.
VIA followed by Gynocular™
|
6 months
|
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination
Time Frame: 6 months
|
To determine estimates of test accuracy for combinations of screening tests, i.e.
Gynocular™ followed by VIA
|
6 months
|
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination
Time Frame: 6 months
|
To determine estimates of test accuracy for combinations of screening tests: HR-HPV followed by VIA.
|
6 months
|
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination
Time Frame: 6 months
|
To determine estimates of test accuracy for combinations of screening tests: VIA followed by HR-HPV.
|
6 months
|
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination subgroup analyses
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Subgroup analyses for the diagnostic test accuracy of Gynocular™: stand alone test
Time Frame: 6 months
|
To investigate the effects of a age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses.
|
6 months
|
Subgroup analyses for the diagnostic test accuracy of VIA: stand alone test
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses.
|
6 months
|
Subgroup analyses for the diagnostic test accuracy of HR-HPV testing: stand alone test
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Subgroup analyses for the diagnostic test accuracy of VIA, HR-HPV testing and Gynocular™: Combined tests
Time Frame: 6 months
|
To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
|
6 months
|
Investigation of Swede Score in WLHIV
Time Frame: 6 months
|
Area under the receiver operating characteristic (ROC) curve for Swede score determined by Gynocular™ in WLHIV
|
6 months
|
Investigation of co-infections of premalignant and malignant disease (STIs/HR-HPV)
Time Frame: 6 months
|
Descriptive analysis of the STI and HR-HPV type distribution associated with each stage of CIN, and when there is persistent disease in WLHIV.
|
6 months
|
Investigation of Trichomonas vaginalis prevalence and persistence in association with menstrual hygiene practices
Time Frame: 6 months
|
Descriptive analysis of the prevalence and persistence of Trichomonas vaginalis in association with vaginal and menstrual hygiene practices.
|
6 months
|
Investigations to inform telemedicine capacity: Comparison of image quality
Time Frame: 6 months
|
Description of image quality from static assessors, in terms of the assessors' ability to adequately evaluate the images.
|
6 months
|
Investigations to inform telemedicine capacity: use of static images
Time Frame: 6 months
|
Proportion of correctly diagnosed CIN2+ through static images obtained by the Gynocular™.
|
6 months
|
Investigations to inform telemedicine capacity: ROC curve for Swede score
Time Frame: 6 months
|
Area under the ROC for static image Swede score obtained by Gynocular™ in WLHIV.
|
6 months
|
Investigations to inform telemedicine capacity: Live versus static assessors
Time Frame: 6 months
|
Cohen's kappa coefficient to assess agreement between live and static assessors.
|
6 months
|
Artificial Intelligence (AI) for improving the detection of precancerous cervical lesions: testing AI algorithm
Time Frame: 6 months
|
Test accuracies of AI deep learning tool retrospectively using coded images obtained in the study through the Gynocular™ and smartphone.
|
6 months
|
Artificial Intelligence for improving the detection of precancerous cervical lesions: improve AI algorithm
Time Frame: 6 months
|
Inform and improve AI deep learning tools to detect HSIL by using images or GIFs obtained in the study through the Gynocular™ and smartphone.
|
6 months
|
Diagnostic test accuracy of AI tool to detect CIN2+/HSIL: other estimates, stand alone
Time Frame: 6 months
|
To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+/HSIL among WLHIV.
|
6 months
|
Diagnostic test accuracy of HR-HPV testing followed by AI tool to detect CIN2+/HSIL: test combination
Time Frame: 6 months
|
To determine estimates of test accuracy for combinations of screening tests, i.e.
HR-HPV followed by AI tool
|
6 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety outcomes: For each adverse event found the investigators will calculate crude frequencies
Time Frame: 9 months
|
Adverse events will be recorded.
The investigators will ask participants to inform the study nurse or assistant if they develop any of these, in person or by phone.
Given the health system in this context is not centralized, it is most efficient to ask participants to report these to the clinical team and investigators.
Information describing these events will include: time of onset, duration, resolution, action to be taken, assessment of intensity, relationship with study treatment.
The clinical team will also complete assessments of seriousness, causality and expectedness.
Participants are asked to inform the clinical team immediately if any AE occur in the 9 months following their initial enrolment.
At each visit, the Study nurse/assistant will also inquire about any adverse events that have occurred, for verification.
For each adverse event found the investigators will calculate crude frequencies.
|
9 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Julia Bohlius, MD, julia.bohlius@ispm.unibe.ch
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 8, 2019
Primary Completion (ANTICIPATED)
January 1, 2021
Study Completion (ANTICIPATED)
December 1, 2022
Study Registration Dates
First Submitted
April 15, 2019
First Submitted That Met QC Criteria
April 24, 2019
First Posted (ACTUAL)
April 30, 2019
Study Record Updates
Last Update Posted (ACTUAL)
November 3, 2020
Last Update Submitted That Met QC Criteria
October 30, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GYNOCULAR
- KFS-4156-02-2017 (OTHER_GRANT: Swiss Cancer Research)
- Esther17G9 (OTHER_GRANT: ESTHER Switzerland)
- U01AI069924 (NIH)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
IPD Plan Description
We plan to publish results in open access journals with data available in accordance with FAIR principles.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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