Screening Strategies Among High-risk Populations for Anal Cancer

Browse trials for

• Neoplasms 9,365

Keywords

• Cancer
• HIV
• Screening

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's planned enrollment of 500 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Lead sponsor

Lisa Flowers is the lead sponsor of 4 studies on the registry; 3 are open to participants now.

Study arms

• Other
  Men with impaired immune status

  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.

  Diagnostic Test: HRA + Biopsy · Diagnostic Test: Anal Cytology · Diagnostic Test: Genotyping of anal hrHPV infection · Diagnostic Test: CINtec®PLUS

• Other
  Men without impaired immune status

  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.

  Diagnostic Test: HRA + Biopsy · Diagnostic Test: Anal Cytology · Diagnostic Test: Genotyping of anal hrHPV infection · Diagnostic Test: CINtec®PLUS

• Other
  Women with impaired immune status and and lower genital tract neoplasia (LGTN)

  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.

  Diagnostic Test: HRA + Biopsy · Diagnostic Test: Anal Cytology · Diagnostic Test: Genotyping of anal hrHPV infection · Diagnostic Test: CINtec®PLUS

• Other
  Women without impaired immune status and lower genital tract neoplasia (LGTN)

  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.

  Diagnostic Test: HRA + Biopsy · Diagnostic Test: Anal Cytology · Diagnostic Test: Genotyping of anal hrHPV infection · Diagnostic Test: CINtec®PLUS

Interventions

• Diagnostic testHRA + Biopsy

  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

  Also known as: HRA and Histology

• Diagnostic testAnal Cytology

  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.

  Also known as: Swab anal Sample

• Diagnostic testGenotyping of anal hrHPV infection

  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)

  Also known as: hrHPV

• Diagnostic testCINtec®PLUS

  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).

  Also known as: P16/Ki-67 dual immunostaining

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.

   Time frame: Baseline

Secondary outcomes

1. DNA methylation markers

   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)

   Time frame: Baseline, 1 year, 2 years

2. Anal immune modulations

   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).

   Time frame: Baseline, 1 year, 2 years

3. aHSIL prevalence

   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.

   Time frame: Baseline

4. aHSIL clearance

   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.

   Time frame: 1 year, 2 years

5. Inflammatory Markers (Il-1RA, IL1β, IL6, IL6sr, TNF-α, and IL-10)

   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.

   Time frame: Baseline, 1 year, 2 years

6. Inflammatory Markers (sTNFR2 and interferon (IFN)-γ)

   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.

   Time frame: Baseline, 1 year, 2 years

7. Inflammatory Marker (CRP)

   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%.

   Time frame: Baseline, 1 year, 2 years

Individual participant data

Plan to share: Yes — All of the individual participant data collected from study participation will be available for sharing after deidentification

Supporting information: Study protocol, Sap