Ignite Creation Date:
2024-05-06 @ 7:25 PM
Last Modification Date:
2024-10-26 @ 3:06 PM
Study NCT ID:
NCT06002126
Status:
RECRUITING
Last Update Posted:
2023-08-21
First Post:
2023-08-14
Brief Title:
Optimization of Cervical Cancer Screening Among Women Living With HIV in Latin American Countries
Sponsor:
Weill Medical College of Cornell University
Organization:
Weill Medical College of Cornell University
Study Overview
Official Title:
Optimization of Cervical Cancer Screening Among Women Living With HIV in Latin American Countries
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cervical cancer is a relatively common cancer among women living with human immunodeficiency virus HIV This study will test women for human papillomavirus HPV infection of the cervix The main purpose of this study is to determine the best way to test for damaged areas of the cervix Damaged areas of the cervix should be treated and removed to prevent cancer of the cervix
Women in this study will be seen once twice or three times in a year Women will provide several samples related to screening for cervical cancer including a swab of the cervix a self-collected swab of the vagina and urine Women will have a detailed examination of the cervix called colposcopy and have a few biopsies or small pinches of the cervix to look for areas at risk for turning into cancer If HPV of the cervix is found but treatment of the cervix is not indicated women will return in 6 months and in 12 months to repeat these tests Most women will only need 1 visit Women found to have damaged areas of the cervix at risk for turning into cancer will be referred for treatment
This protocol will compare different tests to understand the best test to identify women at risk for cervical cancer
Women in this study will be seen once twice or three times in a year Women will provide several samples related to screening for cervical cancer including a swab of the cervix a self-collected swab of the vagina and urine Women will have a detailed examination of the cervix called colposcopy and have a few biopsies or small pinches of the cervix to look for areas at risk for turning into cancer If HPV of the cervix is found but treatment of the cervix is not indicated women will return in 6 months and in 12 months to repeat these tests Most women will only need 1 visit Women found to have damaged areas of the cervix at risk for turning into cancer will be referred for treatment
This protocol will compare different tests to understand the best test to identify women at risk for cervical cancer
Detailed Description:
The overall goal of this research is to develop a point of care high-risk HPV hrHPV test and molecular testing that optimizes specificity to detect high-grade squamous intraepithelial lesions HSIL specifically cervical intraepithelial neoplasia of grade 2 or more CIN 2 in women living with HIV WHIV in Latin America while maintaining high test sensitivity To accomplish this goal the protocol will optimize cervical screening by modifying the cycle thresholdgenotype interpretation of Xpert HPV assay output In a secondary manner the protocol will also evaluate whether triage with HPVhost DNA methylation improves the specificity of Xpert alone
The hypotheses for this protocol includes
The Xpert HPV test can be optimized for HSIL detection CIN2 in WHIV to significantly improve test specificity when compared to unmodified test output using manufacturer guidelines
To evaluate this hypothesis the protocol will enroll 1000 cisgender women or transgender men age 25-65 years living with HIV who are undergoing routine cervical cancer screening These individuals will be recruited from affiliated clinical sites of the National Institute of Public Health in Cuernavaca Mexico and University of São Paulo Brazil Participants will provide a first void urine sample and will be instructed how to self-collect a vaginal swab An oral gargle specimen will be collected for HPV testing HPV methylation and Epstein-Bar Virus EBV co-infection They will receive a baseline questionnaire about risk factors for HPV and cervical cancer and provide a blood specimen for CD4 count plasma viral load DNA methylation of biological aging circulating tumor HPV DNA ctHPVDNA analysis and stored sera Next a provider will collect an anal swab Then the participant will undergo a speculum exam and a provider will collect a cervical cytobroom sample for cytology and HPV testing followed by a swab for stored specimens Finally acetic acid will be applied followed by a digital image of the cervix Then at least two cervical biopsies will be obtained
Material from one provider-collected cervical swab will undergo cervical cytology assessment using Bethesda Criteria Cervical histology results from the collected biopsies will be interpreted according to the Lower Anogenital Squamous Terminology LAST HSIL will be defined as CIN 2 with diffuse p16 staining CIN 2-3 or CIN 3 Women diagnosed with HSIL will be treated according to local standards The local histology result will be used for the management of participants Any lesions suspicious for invasive cancer will be referred to the appropriate specialist Women with HSIL on cytology but no HSIL on histology will be treated according to the local standard The management options include repeat colposcopy endocervical curettage or a diagnostic loop electro-excision procedure Similarly women with a Type 3 transformation zone should have endocervical curettage and be managed according to local standards After local pathology review all histology specimens will be shipped centrally for Histology Endpoint Adjudication these adjudicated histology results will be used for reporting research findings The details of this process will be in the Manual of Procedures Discordance between the local and central pathology review will be adjudicated with a second central pathologist The final histology result will be sent back to the local site and provided to the participant and their providers Women found to have vulvar vaginal or perianal lesions suspicious for HSIL will be referred for appropriate evaluation
The self-collected vaginal swab and material from the provider-collected cytobroom sample will be tested for HPV using Xpert HPV Xpert testing of self- and provider-collected samples will be conducted locally at the point of care in Brazil and Mexico Remaining material from the vaginal and cervical samples will be shipped to Dr Villas lab in Brazil to allow for S5 methylation testing of any WHIV with hrHPV detected Residual samples as well as the collected urine will be stored in Dr Villas lab for future studies
Women with hrHPV detected on a provider-collected cervical sample using a locally available and approved test but who were negative for HSIL as determined by cervical biopsy will be asked to return for a follow-up study visit at 6-month to receive the same procedures described above with the exception of blood draws If at the 6-month follow-up visit WHIV continue to have detection of hrHPV but are HSIL negative by biopsy they will be asked to return for an additional follow-up study visit 6 months later 12-months post-baseline to receive the same procedures We estimate that approximately 40 of the population will have hrHPV detected and may need to return for a follow-up visit and 7 will be HSIL and referred for treatment
The hypotheses for this protocol includes
The Xpert HPV test can be optimized for HSIL detection CIN2 in WHIV to significantly improve test specificity when compared to unmodified test output using manufacturer guidelines
To evaluate this hypothesis the protocol will enroll 1000 cisgender women or transgender men age 25-65 years living with HIV who are undergoing routine cervical cancer screening These individuals will be recruited from affiliated clinical sites of the National Institute of Public Health in Cuernavaca Mexico and University of São Paulo Brazil Participants will provide a first void urine sample and will be instructed how to self-collect a vaginal swab An oral gargle specimen will be collected for HPV testing HPV methylation and Epstein-Bar Virus EBV co-infection They will receive a baseline questionnaire about risk factors for HPV and cervical cancer and provide a blood specimen for CD4 count plasma viral load DNA methylation of biological aging circulating tumor HPV DNA ctHPVDNA analysis and stored sera Next a provider will collect an anal swab Then the participant will undergo a speculum exam and a provider will collect a cervical cytobroom sample for cytology and HPV testing followed by a swab for stored specimens Finally acetic acid will be applied followed by a digital image of the cervix Then at least two cervical biopsies will be obtained
Material from one provider-collected cervical swab will undergo cervical cytology assessment using Bethesda Criteria Cervical histology results from the collected biopsies will be interpreted according to the Lower Anogenital Squamous Terminology LAST HSIL will be defined as CIN 2 with diffuse p16 staining CIN 2-3 or CIN 3 Women diagnosed with HSIL will be treated according to local standards The local histology result will be used for the management of participants Any lesions suspicious for invasive cancer will be referred to the appropriate specialist Women with HSIL on cytology but no HSIL on histology will be treated according to the local standard The management options include repeat colposcopy endocervical curettage or a diagnostic loop electro-excision procedure Similarly women with a Type 3 transformation zone should have endocervical curettage and be managed according to local standards After local pathology review all histology specimens will be shipped centrally for Histology Endpoint Adjudication these adjudicated histology results will be used for reporting research findings The details of this process will be in the Manual of Procedures Discordance between the local and central pathology review will be adjudicated with a second central pathologist The final histology result will be sent back to the local site and provided to the participant and their providers Women found to have vulvar vaginal or perianal lesions suspicious for HSIL will be referred for appropriate evaluation
The self-collected vaginal swab and material from the provider-collected cytobroom sample will be tested for HPV using Xpert HPV Xpert testing of self- and provider-collected samples will be conducted locally at the point of care in Brazil and Mexico Remaining material from the vaginal and cervical samples will be shipped to Dr Villas lab in Brazil to allow for S5 methylation testing of any WHIV with hrHPV detected Residual samples as well as the collected urine will be stored in Dr Villas lab for future studies
Women with hrHPV detected on a provider-collected cervical sample using a locally available and approved test but who were negative for HSIL as determined by cervical biopsy will be asked to return for a follow-up study visit at 6-month to receive the same procedures described above with the exception of blood draws If at the 6-month follow-up visit WHIV continue to have detection of hrHPV but are HSIL negative by biopsy they will be asked to return for an additional follow-up study visit 6 months later 12-months post-baseline to receive the same procedures We estimate that approximately 40 of the population will have hrHPV detected and may need to return for a follow-up visit and 7 will be HSIL and referred for treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U54CA242639 | NIH | None | httpsreporternihgovquickSearchU54CA242639 |