Researchers now know that human papillomavirus (HPV) infection is the necessary but not sufficient cause of cervical cancer. Cervical pathogenesis evolves as follows: normal cervical tissue, to oncogenic HPV infection, to precancer and then to invasive cancer. The majority of women with oncogenic HPV infections will not develop cancer, and most HPV infections, even those with associated cellular changes, regress in 1-2 years, probably eradicated or controlled by cellular immune response. Moreover, while invasive cancer and precancer are histologically well-defined, the histological classification of low-grade lesions, now better defined as HPV infection, is very heterogeneous and poorly reproducible. Identifying women at highest risk for cancer prior to neoplastic progression is therefore a challenge. At present, researchers are unable to predict with any accuracy which HPV infections will progress and which are among the majority that regress. It is therefore of etiologic interest and of public health benefit to develop a method for identifying the HPV-infected women at risk for progressing to precancer and invasion.
In order to develop an accurate and reproducible division of precursor lesions (HPV infection and precancer), researchers must gain knowledge about the molecular distinctions at each progressive disease state. The goal of SUCCEED (Study to Understand Cervical Cancer Early Endpoints and Determinants) is to comprehensively assess biomarkers of risk for progressive cervical neoplasia, and thus develop biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection.
Investigators in DCEG have implemented a cross-sectional study to develop a comprehensive list of potential biomarkers by examining biospecimens and cervical tissues from over 2,500 women with HPV infection, precancer, and cancer. Several HPV-based markers, including HPV genotyping and detection of HPV integration have been evaluated in SUCCEED. A major focus is the evaluation of gene expression profiles to gain an accurate and comprehensive in vivo picture of cervical carcinogenesis. Investigators will validate the most promising identified candidate biomarkers in a prospective design by assessing their predictive values for key outcomes related to progression (HPV persistence, diagnosis of precancer) or non-progression (HPV clearance).
For more information, contact Nicolas Wentzensen.