Uterine Cervical NeoplasmsNCT03931083
Screening Test Accuracy of Gynocular™, HR-HPV Testing, VIA for Detection of Cervical Neoplastic Lesions, in Women Living With HIV
An observational study of Uterine Cervical Neoplasms and HIV/AIDS, run by University of Bern at 1 site in Zambia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Uterine Cervical Neoplasms, HIV/AIDS
- What is being tested?
- Screening for CIN2+/HSIL
- How many people
- 450 participants
- Where
- 1 siteZambia
- Study dates
- 8 May 2019to 1 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Albert Manasyan, MD contact
Zambia1 site, 1 recruiting
- Recruiting
Centre for Infectious Disease Research in Zambia
Lusaka
Albert Manasyan, MD, Albert.Manasyan@cidrz.org
About this study
Official title: 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.
Read the 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.
- Conditions
- Uterine Cervical Neoplasms, HIV/AIDS
- Being tested
- Screening for CIN2+/HSIL
- Medical subject headings
- Uterine Cervical Neoplasms, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Screening for CIN2+/HSILDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Screening for CIN2+/HSIL | |
| 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. Receives: Diagnostic Test: Screening for CIN2+/HSIL | |
| 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. Receives: Diagnostic Test: Screening for CIN2+/HSIL | |
| 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. Receives: Diagnostic Test: Screening for CIN2+/HSIL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Test accuracy (sensitivity, specificity) of the Gynocular™ when used as stand-alone tests to detect CIN2+
To estimate the sensitivity and specificity of the Gynocular when used as a standalone tests to detect CIN2+ among WLHIV.
Measured: 6 months
Test accuracy (sensitivity, specificity) of HR-HPV when used as stand-alone tests to detect CIN2+
To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+ among WLHIV.
Measured: 6 months
Test accuracy (sensitivity, specificity) of VIA when used as stand-alone tests to detect CIN2+
To estimate the sensitivity and specificity of VIA when used as a standalone tests to detect CIN2+ among WLHIV.
Measured: 6 months
Secondary outcomes (30)
Diagnostic test accuracy of the Gynocular™to detect CIN2+/HSIL: other estimates, stand alone
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).
Measured: 6 months
Diagnostic test accuracy of HR-HPV testing to detect CIN2+/HSIL: other estimates, stand alone
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).
Measured: 6 months
Diagnostic test accuracy of VIA to detect CIN2+/HSIL: other estimates, stand alone
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).
Measured: 6 months
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination
To determine estimates of test accuracy for combinations of screening tests, i.e. HR-HPV followed by Gynocular™
Measured: 6 months
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
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
Measured: 6 months
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination
To determine estimates of test accuracy for combinations of screening tests, i.e. Gynocular™ followed by HR-HPV
Measured: 6 months
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination subgroup analyses
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
Measured: 6 months
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination
To determine estimates of test accuracy for combinations of screening tests, i.e. VIA followed by Gynocular™
Measured: 6 months
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
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
Measured: 6 months
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination
To determine estimates of test accuracy for combinations of screening tests, i.e. Gynocular™ followed by VIA
Measured: 6 months
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
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
Measured: 6 months
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination
To determine estimates of test accuracy for combinations of screening tests: HR-HPV followed by VIA.
Measured: 6 months
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
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
Measured: 6 months
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination
To determine estimates of test accuracy for combinations of screening tests: VIA followed by HR-HPV.
Measured: 6 months
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination subgroup analyses
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
Measured: 6 months
Subgroup analyses for the diagnostic test accuracy of Gynocular™: stand alone test
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.
Measured: 6 months
Subgroup analyses for the diagnostic test accuracy of VIA: stand alone test
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.
Measured: 6 months
Subgroup analyses for the diagnostic test accuracy of HR-HPV testing: stand alone test
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
Measured: 6 months
Subgroup analyses for the diagnostic test accuracy of VIA, HR-HPV testing and Gynocular™: Combined tests
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
Measured: 6 months
Investigation of Swede Score in WLHIV
Area under the receiver operating characteristic (ROC) curve for Swede score determined by Gynocular™ in WLHIV
Measured: 6 months
Investigation of co-infections of premalignant and malignant disease (STIs/HR-HPV)
Descriptive analysis of the STI and HR-HPV type distribution associated with each stage of CIN, and when there is persistent disease in WLHIV.
Measured: 6 months
Investigation of Trichomonas vaginalis prevalence and persistence in association with menstrual hygiene practices
Descriptive analysis of the prevalence and persistence of Trichomonas vaginalis in association with vaginal and menstrual hygiene practices.
Measured: 6 months
Investigations to inform telemedicine capacity: Comparison of image quality
Description of image quality from static assessors, in terms of the assessors' ability to adequately evaluate the images.
Measured: 6 months
Investigations to inform telemedicine capacity: use of static images
Proportion of correctly diagnosed CIN2+ through static images obtained by the Gynocular™.
Measured: 6 months
Investigations to inform telemedicine capacity: ROC curve for Swede score
Area under the ROC for static image Swede score obtained by Gynocular™ in WLHIV.
Measured: 6 months
Investigations to inform telemedicine capacity: Live versus static assessors
Cohen's kappa coefficient to assess agreement between live and static assessors.
Measured: 6 months
Artificial Intelligence (AI) for improving the detection of precancerous cervical lesions: testing AI algorithm
Test accuracies of AI deep learning tool retrospectively using coded images obtained in the study through the Gynocular™ and smartphone.
Measured: 6 months
Artificial Intelligence for improving the detection of precancerous cervical lesions: improve AI algorithm
Inform and improve AI deep learning tools to detect HSIL by using images or GIFs obtained in the study through the Gynocular™ and smartphone.
Measured: 6 months
Diagnostic test accuracy of AI tool to detect CIN2+/HSIL: other estimates, stand alone
To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+/HSIL among WLHIV.
Measured: 6 months
Diagnostic test accuracy of HR-HPV testing followed by AI tool to detect CIN2+/HSIL: test combination
To determine estimates of test accuracy for combinations of screening tests, i.e. HR-HPV followed by AI tool
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2019
- Study start8 May 2019
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Uterine Cervical NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Centre for Infectious Disease Research in Zambia, Cervical Cancer Prevention Program in Zambia, International Agency for Research on Cancer
- Responsible party
- Sponsor
- Investigators
- Julia Bohlius, MD, Principal investigator, julia.bohlius@ispm.unibe.ch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03931083
- Sponsor's protocol ID
- GYNOCULAR
- Other IDs
- KFS-4156-02-2017, Esther17G9, U01AI069924
- Status last verified
- Oct 2020
- First submitted
- 15 Apr 2019
- Last updated
- 3 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We plan to publish results in open access journals with data available in accordance with FAIR principles.
Publications
Taghavi K, Moono M, Mwanahamuntu M, Roumet M, Limacher A, Kapesa H, Madliwa T, Rutjes A, Basu P, Low N, Manasyan A, Bohlius J. Accuracy of screening tests for cervical precancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia. BMJ Oncol. 2024 Feb 10;3(1):e000111. doi: 10.1136/bmjonc-2023-000111. eCollection 2024.
PubMed 39886160Taghavi K, Moono M, Mwanahamuntu M, Roumet M, Limacher A, Kapesa H, Madliwa T, Rutjes A, Basu P, Low N, Manasyan A, Bohlius J. Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia. medRxiv [Preprint]. 2023 Jun 1:2023.05.31.23290779. doi: 10.1101/2023.05.31.23290779.
PubMed 37398043Taghavi K, Moono M, Mwanahamuntu M, Basu P, Limacher A, Tembo T, Kapesa H, Hamusonde K, Asangbeh S, Sznitman R, Low N, Manasyan A, Bohlius J. Screening test accuracy to improve detection of precancerous lesions of the cervix in women living with HIV: a study protocol. BMJ Open. 2020 Dec 18;10(12):e037955. doi: 10.1136/bmjopen-2020-037955.
PubMed 33371015
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03931083
- Acronym / sponsor ID
- GYNOCULAR
- Conditions
- Uterine Cervical Neoplasms, HIV/AIDS
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- University of BernUniversity, hospital or other
- Collaborators
- Centre for Infectious Disease Research in Zambia, Cervical Cancer Prevention Program in Zambia, International Agency for Research on Cancer
- Study start
- 8 May 2019 (actual)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 30 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Portable magnification device (Gynocular™) | – | Diagnostic Test: Screening for CIN2+/HSILThe 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. |
| Testing for high risk HPV (HRHPV) | – | Diagnostic Test: Screening for CIN2+/HSILTo 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. |
| Visual inspection with acetic acid (VIA) | – | Diagnostic Test: Screening for CIN2+/HSILVIA, 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. |
| Histopathological examination of tissue biopsies | – | Diagnostic Test: Screening for CIN2+/HSILAll 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Screening for CIN2+/HSILThe 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. | Diagnostic test | Histopathological examination of tissue biopsies, Portable magnification device (Gynocular™), Testing for high risk HPV (HRHPV), Visual inspection with acetic acid (VIA) |
Primary outcome
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.
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.
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.
30 secondary outcomes
Diagnostic test accuracy of the Gynocular™to detect CIN2+/HSIL: other estimates, stand alone
Time frame: 6 months
Diagnostic test accuracy of HR-HPV testing to detect CIN2+/HSIL: other estimates, stand alone
Time frame: 6 months
Diagnostic test accuracy of VIA to detect CIN2+/HSIL: other estimates, stand alone
Time frame: 6 months
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination
Time frame: 6 months
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
Time frame: 6 months
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination
Time frame: 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
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination
Time frame: 6 months
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
Time frame: 6 months
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination
Time frame: 6 months
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
Time frame: 6 months
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination
Time frame: 6 months
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
Time frame: 6 months
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination
Time frame: 6 months
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination subgroup analyses
Time frame: 6 months
Subgroup analyses for the diagnostic test accuracy of Gynocular™: stand alone test
Time frame: 6 months
Subgroup analyses for the diagnostic test accuracy of VIA: stand alone test
Time frame: 6 months
Subgroup analyses for the diagnostic test accuracy of HR-HPV testing: stand alone test
Time frame: 6 months
Subgroup analyses for the diagnostic test accuracy of VIA, HR-HPV testing and Gynocular™: Combined tests
Time frame: 6 months
Investigation of Swede Score in WLHIV
Time frame: 6 months
Investigation of co-infections of premalignant and malignant disease (STIs/HR-HPV)
Time frame: 6 months
Investigation of Trichomonas vaginalis prevalence and persistence in association with menstrual hygiene practices
Time frame: 6 months
Investigations to inform telemedicine capacity: Comparison of image quality
Time frame: 6 months
Investigations to inform telemedicine capacity: use of static images
Time frame: 6 months
Investigations to inform telemedicine capacity: ROC curve for Swede score
Time frame: 6 months
Investigations to inform telemedicine capacity: Live versus static assessors
Time frame: 6 months
Artificial Intelligence (AI) for improving the detection of precancerous cervical lesions: testing AI algorithm
Time frame: 6 months
Artificial Intelligence for improving the detection of precancerous cervical lesions: improve AI algorithm
Time frame: 6 months
Diagnostic test accuracy of AI tool to detect CIN2+/HSIL: other estimates, stand alone
Time frame: 6 months
Diagnostic test accuracy of HR-HPV testing followed by AI tool to detect CIN2+/HSIL: test combination
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
- Derived from this study: PubMed 39886160Taghavi K, Moono M, Mwanahamuntu M, Roumet M, Limacher A, Kapesa H, Madliwa T, Rutjes A, Basu P, Low N, Manasyan A, Bohlius J. Accuracy of screening tests for cervical precancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia. BMJ Oncol. 2024 Feb 10;3(1):e000111. doi: 10.1136/bmjonc-2023-000111. eCollection 2024.
- Derived from this study: PubMed 37398043Taghavi K, Moono M, Mwanahamuntu M, Roumet M, Limacher A, Kapesa H, Madliwa T, Rutjes A, Basu P, Low N, Manasyan A, Bohlius J. Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia. medRxiv [Preprint]. 2023 Jun 1:2023.05.31.23290779. doi: 10.1101/2023.05.31.23290779.
- Derived from this study: PubMed 33371015Taghavi K, Moono M, Mwanahamuntu M, Basu P, Limacher A, Tembo T, Kapesa H, Hamusonde K, Asangbeh S, Sznitman R, Low N, Manasyan A, Bohlius J. Screening test accuracy to improve detection of precancerous lesions of the cervix in women living with HIV: a study protocol. BMJ Open. 2020 Dec 18;10(12):e037955. doi: 10.1136/bmjopen-2020-037955.
- Individual participant dataSharing planned: Undecided. We plan to publish results in open access journals with data available in accordance with FAIR principles.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Manasyan, MD contact
Julia Bohlius, MD principal investigator
julia.bohlius@ispm.unibe.ch
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Uterine Cervical Neoplasms and HIV/AIDS, run by University of Bern at 1 site in Zambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Katayoun Taghavi, MD (+41 31 631 35 23, katayoun.taghavi@ispm.unibe.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Test accuracy (sensitivity, specificity) of the Gynocular™ when used as stand-alone tests to detect CIN2+ (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03931083, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2020.