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It is well-recognized that cytology-based programs have proven successful for prevention of cervical cancer. The incidence of cervical cancer has fallen by 50% or more since introduction of Pap smear screening for cervical cancer detection in developed countries; in the U.S., annual cervical cancer incidence has fallen to ~10,000. Paradoxically, cervical cancer is the second leading cause of cancer among women worldwide, with almost 500,000 new cases diagnosed annually. It is proven that the two necessary determinants of cervical cancer are persistent infection with oncogenic types of human papillomavirus (HPV) and lack of effective screening for treatable cervical precancers, specifically histologically diagnosed as cervical intraepithelial neoplasia grade 3 (CIN3).
However, further substantial improvements in cytology programs are unlikely to be cost-effective. Cervical cytology is insensitive and must be repeated frequently to achieve programmatic effectiveness; in the U.S., billions of dollars are spent annually on the cytology-based program. Effective Pap screening programs often can not be maintained in resource-limited countries and in underserved populations in wealthy countries, primarily because of high cost and loss-to-follow-up. This is a critical problem because cervical cancer occurs mainly in low-resource, underserved regions as part of a complex of diseases linked to poverty and/or racial disparities. There are several important underserved populations in the U.S., including the Mississippi Delta, U.S.-Mexico border areas, and Appalachia.
We are currently initiating several community-based cervical cancer screening “demonstration” projects in underserved U.S. and international populations. The overarching goal of these projects is to validate new approaches to cervical cancer screening, based on HPV DNA detection. We believe that cytology programs will not be the solution to overcoming the disparities in cervical cancer burden and that the superior clinical sensitivity and reliability of HPV DNA detection may be more adaptable to low resource settings. The first of these projects is the Mississippi Delta Project (MDP). The primary goal of MDP is to compare the clinical performance for detection of cervical precancer and cancer of self-collection of cervical specimens and HPV DNA testing versus the current cytology program. If self-collection plus HPV DNA testing proves acceptable and its clinical performance at least equivalent to cytology, this approach might be used as an acceptable alternative to cytology for cervical cancer screening. The reduced number of clinical visits will make self-collection/HPV DNA testing more cost-effective for screening and thus could be used to expand screening into underserved populations, perhaps in collaboration with the CDC.
We are also exploring the possibility of a second study to develop and validate a low-cost, sustainable, same-day screening/treatment strategy based on HPV DNA detection in older women that will complement vaccination strategies aimed at preventing HPV infection in younger women. An affordable, 3-hour HPV test ($3 per test rather than $30 for the current test) will be introduced next year for international evaluation. We are proposing a HPV “screen and treat” clinical trial to demonstrate that a simple and low-cost approach based on this new screening assay can meet or exceed current cytology programs.
We also are actively evaluating new clinical molecular diagnostics for cervical cancer screening. We have several projects to evaluate several new assays, including new HPV assays as well as other biomarker assays that are potentially as sensitive but more specific (i.e., have a better positive predictive value) than HPV DNA detection.
Candidate Fellows will participate in these complimentary activities and thereby receive training in development of field studies and in clinical epidemiology. There will be a strong emphasis for Fellows to take the lead on several projects and analyses and to assist on larger projects, with an ultimate goal of preparing Fellows to become independent, principal investigators.
