Screening Strategies for People With a High Risk of Anal Cancer
- Conditions
- NeoplasmsHPV-Related Anal Squamous Cell Carcinoma
- Interventions
- Diagnostic Test: HRA + BiopsyDiagnostic Test: Anal CytologyDiagnostic Test: Genotyping of anal hrHPV infectionDiagnostic Test: CINtec®PLUS
- 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 minorities with a high risk of anal cancer and 2) characterize DNA methylation, immunologic response, and social determinants 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 living with HIV. The study is important because the incidence of anal cancer is particularly high among certain groups; health disparity further contributes to this high risk among minorities. Findings will provide much-needed evidence for anal cancer screening strategies to reduce health disparities, improve screening outcomes, and decrease the incidence of anal cancer among high-risk minorities. The study population includes Black or Latinx, males - men having sex with men (MSM) only - 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- 30 years of age and older
- Identifies as Black or Latinx,
- Males (MSM only) and females with a known history of high-grade lower genital tract neoplasia (LGTN), Zubrod Performance Status of 0-2;
- Women with Human Papillomavirus (HPV) related cervical, vaginal, or vulvar high-grade precancer or cancer
- 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
- Arm && Interventions
Group Intervention Description HIV Negative MSM with high grade LGTN Anal Cytology At 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. HIV Positive MSM with high grade LGTN HRA + Biopsy At 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. HIV Positive MSM with high grade LGTN Anal Cytology At 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. HIV Positive MSM with high grade LGTN Genotyping of anal hrHPV infection At 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. HIV Negative women with high grade LGTN Anal Cytology At 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. HIV Positive MSM with high grade LGTN CINtec®PLUS At 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. HIV Negative MSM with high grade LGTN HRA + Biopsy At 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. HIV Negative MSM with high grade LGTN Genotyping of anal hrHPV infection At 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. HIV Negative MSM with high grade LGTN CINtec®PLUS At 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. HIV Positive women with high grade LGTN HRA + Biopsy At 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. HIV Positive women with high grade LGTN Anal Cytology At 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. HIV Positive women with high grade LGTN Genotyping of anal hrHPV infection At 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. HIV Positive women with high grade LGTN CINtec®PLUS At 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. HIV Negative women with high grade LGTN HRA + Biopsy At 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. HIV Negative women with high grade LGTN Genotyping of anal hrHPV infection At 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. HIV Negative women with high grade LGTN CINtec®PLUS At 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.
- 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
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
The Ponce Center
🇺🇸Atlanta, Georgia, United States
University of Miami School of Medicine at Jackson Memorial Hospital (JMH)
🇺🇸Miami, Florida, United States