Screening Strategies Among High-risk Populations for Anal Cancer
2 other identifiers
interventional
500
1 country
4
Brief Summary
The goal of the proposed research is to 1) examine the performance of emerging screening methods for anal high-grade squamous intraepithelial lesion (aHSIL), a precancerous condition of anal cancer, among populations at high risk for anal cancer and 2) characterize DNA methylation, immunologic response, and environmental factors associated with aHSIL.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Dec 2024
Typical duration for not_applicable
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 3, 2024
CompletedFirst Posted
Study publicly available on registry
October 8, 2024
CompletedStudy Start
First participant enrolled
December 16, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2027
September 8, 2025
September 1, 2025
2.8 years
October 3, 2024
September 2, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Specificity and Sensitivity of screening markers
Sensitivity and specificity will be calculated for each of the proposed screening markers separately and a combination of two and three markers for the detection of aHSIL at baseline. The combination of the two and three markers of primary interest includes CINtec®PLUS +hrHPV, CINtec®PLUS+anal cytology, hrHPV+anal cytology, and CINtec®PLUS+hrHPV+anal cytology. The analysis will be performed for the four high-risk groups together and stratified by the four high-risk categories.
Baseline
Secondary Outcomes (7)
DNA methylation markers
Baseline, 1 year, 2 years
Anal immune modulations
Baseline, 1 year, 2 years
aHSIL prevalence
Baseline
aHSIL clearance
1 year, 2 years
Inflammatory Markers (Il-1RA, IL1β, IL6, IL6sr, TNF-α, and IL-10)
Baseline, 1 year, 2 years
- +2 more secondary outcomes
Study Arms (4)
Men with impaired immune status
OTHERAt each study visit, participants will receive a digital anorectal examination followed by HRA, with directed biopsies of suspicious lesions. An HRA-certified physician will collect anal swabs and HRA-directed biopsies for histological confirmation of disease and biomarker assays.
Men without impaired immune status
OTHERAt each study visit, participants will receive a digital anorectal examination followed by HRA, with directed biopsies of suspicious lesions. An HRA-certified physician will collect anal swabs and HRA-directed biopsies for histological confirmation of disease and biomarker assays.
Women with impaired immune status and high grade LGTN
OTHERAt each study visit, participants will receive a digital anorectal examination followed by HRA, with directed biopsies of suspicious lesions. An HRA-certified physician will collect anal swabs and HRA-directed biopsies for histological confirmation of disease and biomarker assays.
Women without impaired immune status with high grade LGTN
OTHERAt each study visit, participants will receive a digital anorectal examination followed by HRA, with directed biopsies of suspicious lesions. An HRA-certified physician will collect anal swabs and HRA-directed biopsies for histological confirmation of disease and biomarker assays.
Interventions
High-Resolution Anoscopy, or HRA, is a standard of care procedure for screening and detection of premalignant lesions of the anus. Using a small, thin round tube called an anoscope, the anal canal is examined with a high-resolution magnifying instrument called a colposcope. The application of a mildly acidic liquid on the anal canal facilitates the evaluation of abnormal tissue such as anal dysplasia. Biopsies for histological confirmation of disease will be taken. Biopsies' reporting will follow the terminology, criteria, and recommendations of the Lower Anogenital Squamous Terminology (LAST) project. Histology results will be reported as benign, condyloma acuminatum, AIN grades 1-3, or cancer. For the proposed project, aHSIL+ will be defined as AIN2 (p16 block-positive), AIN3, and cancer at the HRA encounter. All other cases will be classified as \<aHSIL, including benign, condyloma acuminatum, and AIN1
Anal cytology collection (swab samples) will be performed as part of the standard of care during this study. The collected cells, suspended in the SurePath liquid-based medium, will be placed on a slide and microscopically examined by a board-certified pathologist. The sample will then be interpreted using the Bethesda System: negative for intraepithelial lesion or malignancy (NILM), ASCUS, LSIL, ASC-H, or HSIL. Pathologists interpreting the anal cytology will be blinded from hrHPV testing and biopsy histology.
Samples of exfoliated cells from the anal canal will be collected with Dacron swabs. To identify the infecting HPV genotype, DNA will be extracted from swab samples collected with the MagNA Pure LC DNA Isolation Kit III and an LC MagNA Pure system (Roche Diagnostics GmbH, Mannheim, Germany), followed by HPV typing using the TypeSeq assay, a laboratory prepared high-throughput next-generation sequencing assay developed by NCI will be performed as described. The assay uses three sequential PCR steps resulting in barcoded L1 amplicons sequenced and submitted to a bioinformatics pipeline for typing. This TypeSeq assay qualitatively detects and identifies 51 HPV genotypes (HPV types 3, 6, 11, 13, 16, 18, 26, 28, 30, 31, 32, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 67, 68, 69, 70, 71, 72, 73, 74, 76, 81, 82, 83, 84, 85, 86, 87, 89, 90, 91, 97, and 114), including 14 high-risk (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68)
Samples of exfoliated cells from the anal canal will be collected with Dacron swabs. Dual immunostaining with p16/Ki-67 will be performed on the residual cytologic specimen by Roche MTM Laboratories (Heidelberg, Germany), using the CINtec®PLUS Kit according to the manufacturer's instructions. The anal cytology material will be stained with a mouse monoclonal antibody directed against human p16INKa (p16) protein (clone E6H4) and recombinant rabbit monoclonal antibody directed against human Ki-67 protein (clone 274-11AC3V1), using the BenchMark ULTRA instrument (Ventana Roche). Samples with insufficient cellularity will be excluded from the evaluation. A trained cytotechnologist will review all cases for cells staining positively with both markers. A slide will be considered positive if 1 or more squamous epithelial cell(s) stained positive for both p16 and Ki-67 and dual stain-positive cells will be semi-quantitatively assessed (0, 1, 2-5, 6-50, \>50).
Eligibility Criteria
You may qualify if:
- years of age
- Individuals with chronic impaired immune status
- History of high-grade lower genital tract neoplasia (LGTN), Zubrod Performance Status of 0-2;
You may not qualify if:
- Patients treated for aHSIL less than 6 months before screening,
- History of anal cancer and pregnant women.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Lisa Flowerslead
- National Cancer Institute (NCI)collaborator
Study Sites (4)
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
University of Miami School of Medicine at Jackson Memorial Hospital (JMH)
Miami, Florida, 33136, United States
Grady Memorial Hospital
Atlanta, Georgia, 30303, United States
The Ponce Center
Atlanta, Georgia, 30308, United States
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lisa Flowers, MD, MPH
Emory University
- PRINCIPAL INVESTIGATOR
Canhua Xiao, PhD, RN
Emory University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- SCREENING
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor of Medicine
Study Record Dates
First Submitted
October 3, 2024
First Posted
October 8, 2024
Study Start
December 16, 2024
Primary Completion (Estimated)
October 1, 2027
Study Completion (Estimated)
October 1, 2027
Last Updated
September 8, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data will be available for sharing after publication.
- Access Criteria
- Data will be shared upon request with researchers who provide a methodologically sound proposal to achieve the aims in the approved proposal. To gain access, data requesters will need to sign a data access agreement.
All of the individual participant data collected from study participation will be available for sharing after deidentification