Trial Title:
Optimization of Cervical Cancer Screening Among Women Living With HIV in Latin American Countries
NCT ID:
NCT06002126
Condition:
Cervix Cancer
HPV Infection
Cervical High Grade Squamous Intraepithelial Lesion
HIV Infections
Conditions: Official terms:
Infections
Communicable Diseases
Papillomavirus Infections
Uterine Cervical Neoplasms
Conditions: Keywords:
HPV
cervical cancer screening
women with HIV
DNA methylation
extended HPV genotyping
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
Xpert HPV
Description:
The Cepheid Xpert HPV Assay (Xpert HPV) is a qualitative, real-time polymerase chain
reaction (PCR) assay for the detection of hrHPV DNA. The assay is formatted in a
single-use, Xpert HPV test cartridge and is run on the Cepheid Xpert® System, a
multi-analyte, random access, molecular-diagnostic platform ranging in capacity from 1 to
80 test processing modules. Importantly, a single hrHPV DNA test can be completed in one
hour, permitting same-day screening and diagnosis (e.g. colposcopy) or treatment (e.g.
cryotherapy), reducing the potential for loss to follow-up in lower-resource settings. It
uses liquid-based cytologic media and yields five separate results or channels: HPV16,
HPV18/45, HPV 31/33/35/52/58, HPV51/59, HPV39/68/56/66 all with a corresponding cycle
threshold.
Arm group label:
Cervical cancer screening (single arm)
Intervention type:
Diagnostic Test
Intervention name:
S5 DNA methylation classifier
Description:
The S5 classifier is a combination of DNA methylation levels of the late regions of the
L1 and L2 proteins from HPV16, HPV18, HPV31, and HPV33, as well as DNA methylation of the
promotor region of the human tumor suppressor gene, Erythrocyte Membrane Protein Band 4.1
Like 3 (EPB41L3).
Arm group label:
Cervical cancer screening (single arm)
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.
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 threshold/genotype interpretation of Xpert HPV assay
output. In a secondary manner, the protocol will also evaluate whether triage with
HPV/host 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. Villa's 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. Villa's 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria
- HIV-1 infection, as documented by 1) any FDA approved, licensed HIV rapid test
performed in conjunction with screening (oral immunoblot, enzyme-linked
immunoassay-ELISA, test kit, and confirmed by Western blot or other approved test),
OR 2) a physician's written record that documents HIV infection with supporting
information on the participant's relevant medical history and/or current management
of HIV infection, OR 3) documentation of a prescription of an approved
antiretroviral regimen by either possession of pill bottles or packages with
prescriber's name or antiretrovirals (ARVs) dispensed from an HIV clinical treatment
program with two participant identifiers affixed to the bottles or packages.
- Cisgender women or transgender men.
- Aged 25 to 65.
- Ability to understand and the willingness to sign a written informed consent
document by the participant or by the legal representative(s) of the participant.
Exclusion Criteria
- History of cervical, vulvar, vaginal, perianal, anal cancer or oral cancer.
- Have undergone cervical cancer screening in the last 6 months.
- Have undergone cervical HSIL treatment in the past year.
- Have a history of hysterectomy with removal of the cervix.
- Have never had sexual intercourse (oral or genital or anal).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection (including opportunistic infections of Acquired Immunodeficiency
Syndrome-AIDS and/or genitourinary infections), symptomatic congestive heart
failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study due to the lack of safety data of
performing colposcopy during pregnancy.
- Any other medical condition or social situation that would put the participant, the
study staff, or the study outcomes at risk, as determined by the site investigators.
Gender:
Female
Gender based:
Yes
Gender description:
The study will enroll cisgender women and transgender men.
Minimum age:
25 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of São Paulo
Address:
City:
São Paulo
Zip:
05403-911
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Lenice Galan de Paula
Phone:
55-11-2661-7554
Email:
lenice.galan@hc.fm.usp.br
Investigator:
Last name:
Luisa L Villa, PhD
Email:
Principal Investigator
Facility:
Name:
National Institute of Public Health, Mexico
Address:
City:
Cuernavaca
Zip:
62209
Country:
Mexico
Status:
Recruiting
Contact:
Last name:
Alejandra J Portillo Romero, MD
Email:
alejandra.portillo@insp.mx
Investigator:
Last name:
Eduardo C Lazcano Ponce, MD
Email:
Principal Investigator
Start date:
August 2, 2023
Completion date:
January 1, 2026
Lead sponsor:
Agency:
Weill Medical College of Cornell University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Collaborator:
Agency:
University of Sao Paulo
Agency class:
Other
Collaborator:
Agency:
Mexican National Institute of Public Health
Agency class:
Other
Collaborator:
Agency:
University of California, San Diego
Agency class:
Other
Collaborator:
Agency:
Albert Einstein College of Medicine
Agency class:
Other
Source:
Weill Medical College of Cornell University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06002126
