As millions of HIV-infected Africans live longer due to effective antiretroviral therapy (ART), their incidence of diseases of aging, including cancer, will increase. Human papillomavirus (HPV) is the causal agent for almost all cervical and anal cancers, and ~50% of head and neck cancers. Cervical cancer, an AIDS-defining malignancy, is the most common cause of cancer deaths in women worldwide if not prevented through screening programs. The transforming capability of HPV is enhanced in HIV-infected women, whose HPV-related cervical lesions are more prevalent, more likely to progress, and more likely to become cancer. HPV also causes transformation of the anal mucosa. Unlike AIDS related Kaposi's Sarcoma and non-Hodgkin's Lymphoma, the incidence of cervical and anal cancers has not declined with the introduction of ART and remains elevated several fold in HIV-infected women and men. We propose a research consortium of Albert Einstein College of Medicine with the University of Rwanda (UR-academic partner) and Rwanda Military Hospital (RMH-clinical partner) to investigate HIV/HPV related cancers in Africa. Working with our trainees and partners and continuing to build upon our research infrastructure, all accomplished through our NCI/Fogarty-funded (D43) program "Developing Rwandan Research Capacity in AIDS Malignancies", we will develop a platform establishing the Rwanda-Einstein Consortium as a regional resource for HIV/HPV related clinical, translational and operational research. We will investigate the optimal approach for screening and prevention of cervical cancer in HIV-infected Rwandan women, and assess the cost-effectiveness of different combinations of molecular tests in predicting cervical disease. We will also establish a cohort of Rwandan men who have sex with men (MSM) to determine the prevalence of HIV, type-specific HPV (anal and penile) and anal neoplasia, and follow them for two years to assess incidence of HIV, HPV and anal disease. We will continue to develop the human and physical pathology resources of our clinical partner RMH;establish a PCR laboratory that can perform HPV DNA typing but can be flexibly deployed to assess other pathogens. We will strengthen the Research Offices of RMH and UR with the goal of transferring to them the administrative and financial management and leadership of the Consortium over time. The Consortium resources will allow future assessment of important HPV-related clinical questions, such as HPV types found in vaccinated HIV+ and HIV-negative young Rwandan women, the contribution of HPV to head and neck cancers in HIV+.
HPV associated cancers are significant causes of morbidity and mortality and are not decreasing with the use of antiretroviral therapy, as has been seen with other HIV-associated malignancies. Thus developing a regional hub for translational research in HPV/HIV associated cancers in Rwanda, which has invested in controlling both HIV and HPV disease, will be a key resource in understanding how to mitigate the impact of HIV and HPV on the health of Africans