R01CA256660

The effectiveness of screening women with lower genital tract neoplasia or cancers for anal cancer precursors - project summary/abstract

We recently reported that SCCA incidence (particularly advanced-stage disease) and mortality rates are increasing rapidly (>3% per year) in the US, with notable (>5%/year) increases in women 50 years and older. This shows that SCCA is one of the fastest accelerating causes of cancer incidence and mortality among all cancer sites. Women with lower genital tract (cervical/vaginal/vulvar) dysplasia or cancer (WLGTN) represent a large population (>200,000 new cases per year) at elevated risk of developing SCCA.

We and others have shown that the incidence of SCCA among WLGTN aged 50 years and older is over 20 per 100,000 persons, which is both comparable to the incidence rate among women with HIV (who are the focus of current screening efforts) and is similar to the cervical cancer incidence prior to widespread screening. Furthermore, HPV vaccination is unlikely to decrease SCCA incidence in this population both because WLGTN have already been exposed to oncogenic HPV, and vaccine rates remain low among US women. This highlights an urgent need for studies evaluating possible targeted prevention in the form of anal cancer screening.

Our goal is to evaluate the benefits and harms of SCCA screening among WLGTN. Screening for SCCA involves the identification of precancerous anal lesions (high-grade squamous intraepithelial lesions or "AHSILs") using cytopathologic testing or HPV testing (potentially performed by patients themselves). These lesions (if histologically confirmed) can then be treated, thereby preventing carcinoma development, similar to practices widely endorsed for cervical cancer. To inform guidelines, data regarding screening characteristics, natural history, patient acceptability, the benefits and harms, and cost-effectiveness of screening for SCCA among WLGTN are urgently needed.

We therefore propose a two-site, two-year longitudinal study of 350 HIV uninfected WLGTN aged =45 years. The results of this longitudinal study will be used to synthesize a mathematical (simulation) model that will estimate clinical and population-level benefits versus harms and cost-effectiveness associated with different screening approaches. The specific aims are: (1A) to evaluate the respective screening test characteristics of anal cytology, clinician-collected and self-collected high-risk HPV (HRHPV) testing, and cytology/HRHPV cotesting compared to the gold standard of high-resolution anoscopy (HRA) exam with biopsy; (1B): to determine baseline anal HRHPV and histologic AHSIL (HAHSIL) prevalence and longitudinal risk among WLGTN; (2): to compare patient acceptability and experiences for anal cancer screening strategies among WLGTN; and (3): to develop a mathematical model determining the potential mortality and morbidity benefits, harms, and cost-effectiveness of anal dysplasia screening and/or HRHPV testing in WLGTN.

In summary, the proposed multidisciplinary study will generate much-needed data regarding the optimal SCCA screening approach for WLGTN, necessary to inform national screening recommendations for WLGTN. This study will have direct implications for clinical cancer prevention practices.

Icahn School Of Medicine At Mount Sinai

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

New York, New York 100296504 United States

Single Zip Code

Cancer Prevention and Control Clinical Trials Grant Program (R01 Clinical Trial Required) (PAR-18-559)

Amendment Since initial award the End Date has been extended from 08/31/26 to 08/31/27 and the total obligations have increased 367% from $916,003 to $4,277,018.