Core-005 (Shared Res)

Investigations of HPV related malignancies are heavily dependent on laboratory testing, both to measure the outcomes (cancer, pre-cancer, intraepithelial neoplasia) and to define the possible predictors (e.g. high-risk HPV types). Several new molecular diagnostic tests are becoming available, including HPV genotypes and E6/E7 molecular testing, that can be performed in lower resource settings. Thus the development of Rwanda as a regional hub for HPV/HIV translational research requires rigorous skills in histopathology and in flexible platforms for molecular testing. The Consortium proposes major studies on cervical cancer screening in HIV-positive women, and anal and penile prevalence of HPV in HIV-positive and -negative men who have sex with men (MSM). We also project pilot projects investigating other HPV related malignancies?e.g. squamous cell carcinoma of the conjunctiva (SCCC) and head and neck (SCCHN), as well as studying anal HPV in HIV+ women, and oral-genital concordance of HPV types found in HIV+ and negative MSM. With capacity building, much of the necessary laboratory testing can be done in Africa. We will develop a shared resource in laboratory support for HPV related research, both in histopathology and in molecular testing., including several promising, highly specific new biomarkers that have been reported in HIV-negative women including 1) E6/E7 HPV viral oncoprotein detection (which showed promising results in our large studies in China) and 2) Ki-67 and Topo2a mRNA. We will also establish a PCR lab for HPV genotyping, important now in assessing cervical and anal cancers, and in the future for monitoring and evaluation of vaccine impact in HIV-infected and -uninfected women. The PCR lab will support all Consortium projects: cervical, anal, and potential pilot projects of oral HPV and head and neck cancers. Drs. Tiffany Hebert and Joel Palefsky will direct the Shared Resources Core. Dr. Hebert will continue to lead the pathology capacity building. Dr. Palefsky will direct the development of the new molecular diagnostic testing capabilities.