Screening Strategies Among High-risk Populations for Anal Cancer

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест HRA + 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 follo
• Диагностический тест Anal 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 b
• Диагностический тест Genotyping 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 ste
• Диагностический тест CINtec®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

Первичные конечные точки

• Specificity and Sensitivity of screening markers [Срок оценки: Baseline]

Вторичные конечные точки (7)

• DNA methylation markers [Срок оценки: Baseline, 1 year, 2 years]
• Anal immune modulations [Срок оценки: Baseline, 1 year, 2 years]
• aHSIL prevalence [Срок оценки: Baseline]
• aHSIL clearance [Срок оценки: 1 year, 2 years]
• Inflammatory Markers (Il-1RA, IL1β, IL6, IL6sr, TNF-α, and IL-10) [Срок оценки: Baseline, 1 year, 2 years]
• Inflammatory Markers (sTNFR2 and interferon (IFN)-γ) [Срок оценки: Baseline, 1 year, 2 years]
• Inflammatory Marker (CRP) [Срок оценки: Baseline, 1 year, 2 years]

Критерии участия

Критерии включения

• 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;

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Скрининг

Центры проведения

США · 4 центра

• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami
• University of Miami School of Medicine at Jackson Memorial Hospital (JMH) — Miami
• Grady Memorial Hospital — Atlanta
• The Ponce Center — Atlanta

Идентификаторы

NCT: NCT06628570 · STUDY00006091 · R01CA285198

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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