Determinants of Participation in an Anal Cancer Prevention Trial

Investigator: Joel Palefsky, MD
Sponsor: NIH National Cancer Institute

Location(s): United States


The project, "Determinants of participation in an anal cancer prevention trial" is designed to provide information that will be critical to the performance of a pivotal randomized clinical trial of screening and treatment of anal intraepithelial neoplasia (AIN) to prevent anal cancer. Anal cancer is a growing problem in the United States. Increasing by approximately 2 percent per year among both men and women in the general population, it is particularly common among certain high-risk groups such as HIV-positive men and women. Among HIV-positive individuals, the incidence of anal cancer has continued to increase despite the availability of effective anti-retroviral therapy (ART). The current incidence of anal cancer among HIV-positive men who have sex with men (MSM) may be as high as 137/100,000, or more than 10 times the current incidence of cervical cancer in the screened population of women in the U.S., and is higher than the highest incidence of cervical cancer in unscreened populations of women world-wide. The incidence of anal cancer is almost 7-fold higher among HIV-positive women compared with the general population. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) and is preceded by a series of precancerous changes known as anal intraepithelial neoplasia (AIN). The incidence of cervical cancer has been sharply reduced by screening with cervical cytology to identify women with high-grade cervical intraepithelial neoplasia (CIN), which is then treated to prevent progression to cancer. Like cervical cancer anal cancer may be preventable through treatment of the anal equivalent, high-grade AIN (HGAIN). The combination of an unacceptably high incidence of anal cancer with the likelihood that anal cancer is preventable calls for urgent intervention. At this time however, there are no formal guidelines recommending anal screening and treatment of HGAIN. This is because no studies have yet been done to demonstrate that screening for and treatment of HGAIN reduced the incidence of anal cancer. The USPHS guidelines for the care of HIV-positive individuals currently state that "anal cytology screening of HIV-seropositive MSM and of women may be useful preventive measures. However, studies of screening and treatment programs for AIN 2 or 3 need to be implemented before definitive recommendations for anal cytology screening can be made". This application will provide critical information that will support the conduct of such a study, namely determinants of participation in a randomized clinical trial in which 50 percent of participants with HGAIN will be screened and treated, and 50 percent will be observed without treatment. At the end of a 5-year period, the number of anal cancer cases will be compared in both arms. Given the complexities of the underlying clinical issues that might govern willingness to participate, the increasing proportion of underrepresented minorities that comprise the HIV epidemic and the varying issues around participation that each of these racial/ethnic groups might have, a rigorous study to measure these determinants in geographically and racially/ethnically diverse groups that comprise the HIV epidemic in the U.S. is critical. The specific aims of this application are therefore to: 1. To identify and assess the determinants of provider willingness to refer eligible participants; 2. To identify and assess the determinants of patient willingness and motivation to participate in the RCT; and 3. To determine the optimum study design and sample size, and recruitment strategies based on the analysis of data from Aims 1 and 2. This application is responsive to this challenge topic in which data from earlier observational studies would be augmented with physician and patient acceptability data to permit the pivotal RCT to proceed. Although the results of the RCT will set standard of care for HIV-positive men and women, they will also have wide implications beyond that of the HIV-positive population. The results will guide screening and treatment for HIV-negative populations as well, and the study will provide a biobank of clinical specimens that will be invaluable to understanding molecular determinants of progression from anal intraepithelial neoplasia to anal cancer. These results will also be applicable to understanding the factors underlying progression to cervical cancer, and will be particularly important since assembly of such as biobank of women at risk for cervical cancer would be currently impossible given that the standard of care is to treat high-grade CIN to prevent cervical cancer. Finally, this study will have broad influence by informing strategies to enhance participation in clinical studies by underrepresented minority groups. The incidence of anal cancer among people with HIV is higher than cervical cancer was before routine cervical cytology screening was introduced, but unlike cervical cancer, there are currently no screening recommendations in place for anal cancer. The proposed focus group/survey study will be essential to planning a large definitive randomized controlled trial (RCT) in HIV-positive men and women to test whether treatment of anal cancer precursors identified through anal cytology screening can prevent anal cancer. The RCT planned with the assistance of this proposed study will set the standard of care for HIV- positive men and women, but will also have wide implications for screening and treatment for HIV- negative populations, as well as understanding the factors underlying progression to cervical and anal cancer.