The interaction of human papillomavirus (HPV) with human immunodeficiency virus (HIV) represents one of the most "dangerous liaisons" for women in Sub-Saharan Africa. In high-income countries, the most common of these high-risk HPVs (HR-HPVs) are HPV 16 and 18, which are the targets of two commercially available bivalent and quadrivalent vaccines. However, a wider spectrum of HR-HPV types and a higher incidence of multiple HPV infections have been reported in women from low- to middle-income countries (LMCs). Worldwide, it is estimated that over 500,000 cases of cervical cancer are diagnosed yearly, with 85% of these in LMCs. In Africa, approximately 80,000 women are diagnosed with cervical cancer and 60,000 die from the disease annually, making it the leading cause of cancer death among women. Sub-Saharan Africa also contains 70% of the world's diagnosed cases of HIV, with Kenya as one of Africa's epicenters. Recent studies show that HIV is clearly a contributing factor for cervical carcinogenesis;HIVinfected women have a greater incidence and persistence of HPV infections and suffer from a markedly higher incidence of cervical cancer and cervical intraepithelial neoplasia (CIN). The "perfect storm" of these two families of viruses only begins to explain why both incidence and mortality of cervical cancer in Sub- Saharan Africa are three-fold that of the United States. Other co-morbidity factors, such as sexually transmitted infections (STIs), environmental issues, anti-retroviral and other therapies, and their relation to HR-HPV carcinogenesis, need further study if a major impact is to be made in cervical cancer. The core objective of this application is to better understand the natural history of oncogenic HPV infections in HIV-infected Kenyan women, and the potentially modifiable (and non-modifiable) factors that are associated with progression of oncogenic HPV infection to clinical disease, including cervical cancer. Additionally, with the creation of a multinational, transdisciplinary program entitled the AMPATH-Oncology Institute, a mentoring program will be established to foster development of new cancer researchers in Kenya. Our expected outcome is the establishment of a dedicated core of cancer-focused Kenyan investigators who embody a culture of translational and collaborative research.
This work has significant relevance to public health. Understanding and addressing the modifiable co-factors described above could have profound implications on strategies to address cervical cancer in low to middle income countries beyond implementation of HPV 16/18-based vaccines (even if made affordable) and current screen and treat approaches for patients with abnormal Visual Inspection with Acetic Acid (VIA).