Screening Strategies Among High-risk Populations for Anal Cancer

Not Applicable

Recruiting

• Conditions: Neoplasms; HPV-Related Anal Squamous Cell Carcinoma

• Registration Number: NCT06628570
• Lead Sponsor: Lisa Flowers

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.

Detailed Description

Anal cancer, caused by persistent infection with high-risk human papillomavirus (hrHPV), is typically preceded by anal high-grade squamous intraepithelial lesions (aHSIL). The incidence and mortality of advanced anal cancer has been increasing in the U.S., with the greatest burden of disease and mortality in individuals with chronic impairment of the immune system. The study is important because the incidence of anal cancer is particularly high among certain groups. Findings will provide much-needed evidence for anal cancer screening strategies to reduce incidence of anal cancer and improve health outcomes. The study population includes individuals with chronic impairment of the immune system and females with a known history of high-grade lower genital tract neoplasia.

The study procedures include filling out self-reported questionnaires and collecting biosamples for study-related assays. HRA is part of the standard clinic procedure for this group of participants. Collected biosamples will be banked for future research use. In-person or remote signed consent may occur for the study.

Study Timeline

• Study First Submitted: 2024-10-03
• Study First Submitted QC: 2024-10-03
• Study First Posted: 2024-10-08
• Study Start: 2024-12-16
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-02
• Last Update Posted: 2025-09-08
• Primary Completion: 2027-10
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• 30-80 years of age
• Individuals with chronic impaired immune status
• History of high-grade lower genital tract neoplasia (LGTN), Zubrod Performance Status of 0-2;

Exclusion Criteria

• Patients treated for aHSIL less than 6 months before screening,
• History of anal cancer and pregnant women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Specificity and Sensitivity of screening markers	Baseline	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.

Secondary Outcome Measures

Name	Time	Method
DNA methylation markers	Baseline, 1 year, 2 years	In these models, aHSIL status at baseline will be considered as the response, and each anal DNA methylation marker will be the predictor. Separate models will be performed for each methylation marker (ZNF582, ASCL1, ZIC1, SST, LHX8, WDR17, and ST6GALNAC5)
Anal immune modulations	Baseline, 1 year, 2 years	High-risk HPV 16 persistent patients (N=10) vs. patients with no HPV at least two consecutive times (N=10). Each of the groups will also include aHSIL+ (N=5) vs. \<aLSIL (N=5).
aHSIL prevalence	Baseline	The prevalence of HSIL will be estimated as the proportion of participants who are HRA positive for HSIL at entry and its 95% confidence interval. Logistic regression analysis will be used to evaluate the association of potential risk factors with diagnosis of HSIL.
aHSIL clearance	1 year, 2 years	Only people treated with aHSIL will be used for the clearance analysis. Clearance (HRA biopsy-proven) will be defined as no detectable aHSIL at the immediate one-year (for those with baseline aHSIL) or two-year (for those with newly diagnosed aHSIL cases at the one-year visit) follow-up visit after aHSIL treatment.
Inflammatory Markers (Il-1RA, IL1β, IL6, IL6sr, TNF-α, and IL-10)	Baseline, 1 year, 2 years	Anal swab concentrations of inflammatory markers (IL1ra, IL1β, IL6, IL6sr, TNF-α, and IL-10) will be determined using multiplex assays (Meso Scale Discovery, Rockville, MD) according to the manufacturer's protocol. All samples will be run in duplicates, and mean intra- and inter-assay CVs will be calculated and expected to be \<10%. These inflammatory markers have been reliably found to be elevated in inflammatory-associated diseases including anal inflammation.
Inflammatory Markers (sTNFR2 and interferon (IFN)-γ)	Baseline, 1 year, 2 years	Anal swab concentrations of inflammatory markers of inflammatory markers (sTNFR2 and interferon (IFN)-γ) will be determined using multiplex assays (Meso Scale Discovery, Rockville, MD) according to the manufacturer's protocol.
Inflammatory Marker (CRP)	Baseline, 1 year, 2 years	Anal swab concentrations of inflammatory markers (CRP) will be determined using multiplex assays (Meso Scale Discovery, Rockville, MD) according to the manufacturer's protocol. All samples will be run in duplicates, and mean intra- and inter-assay CVs will be calculated and expected to be \<10%.

Trial Locations

Locations (4)

University of Miami Miller School of Medicine-Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

University of Miami School of Medicine at Jackson Memorial Hospital (JMH); 🇺🇸 Miami, Florida, United States

Grady Memorial Hospital; 🇺🇸 Atlanta, Georgia, United States

The Ponce Center; 🇺🇸 Atlanta, Georgia, United States