Overall Abstract Sub-Saharan Africa contains 70% of the world?s diagnosed cases of HIV/AIDS, with both Uganda and Kenya at its epicenter (12% and 7% prevalence, respectively). Within East Africa, cervical cancer remains one of the most common malignancies in women. HIV is a contributing factor for cervical carcinogenesis with HIV-infected women having a greater incidence and persistence of human papilloma virus (HPV) infections, cervical cancer, and precancerous cervical lesions. In contrast to other HIV-associated cancers, the incidence of cervical cancer has not declined in the era of antiretroviral therapy. The core objective of this application is to better elucidate the natural history of HPV infection and cervical cancer in HIV-infected women, including the cofactors involved in carcinogenesis, the persistence and progression of cervical intraepithelial neoplasia (CIN) after LEEP, and to identify new viral and cellular biomarkers that will assist in screening, triage and treatment. Our central hypothesis is that the incidence, persistence, and spectrum of high risk (HR) HPV are substantially greater in HIV-infected East African women, and that this explains the higher incidence of cervical neoplasia. We further hypothesize that these and other modifiable factors, such as aflatoxin ingestion, disproportionately and adversely influence outcomes of local therapies such as Loop Electrosurgical Excision Procedure (LEEP) in HIV-infected women.
The specific aims for the East Africa Consortium for HPV and Cervical Cancer (EACHC) in Women Living with HIV/AIDS are:
Specific Aim 1. To establish a sustainable research infrastructure for an international partnership to conduct impactful research in HPV and cervical cancer in women living with HIV/AIDS Specific Aim 2. To design and execute three integrated projects that advance the knowledge of the environmental and biologic factors leading to cervical cancer in East Africa: Project 1- Preventing cervical cancer in HIV-infected women Project 2- Understanding CIN2+ among HIV infected women after LEEP: An epidemiological and immunohistochemical study Project 3- Determining biological and viral factors associated with clinical progression of cervical dysplasia in HIV-infected women Specific Aim 3. To increase the research workforce capacity in East Africa through mentoring, training programs and targeted pilot projects
Overall Narrative Worldwide, cervical cancer remains one of the most common malignancies in women, particularly in those who are HIV-infected. The core objective of this application is to better elucidate the natural history of human papillomavirus infection and the development of cervical cancer in HIV-infected women. These include to clarify the cofactors involved in carcinogenesis, the persistence and progression of cervical intraepithelial neoplasia (CIN) after local therapies, and to identify new viral and cellular biomarkers that will ultimately assist in screening, triage and treatment.
