Einstein/Rwanda/DRC Consortium for Research in HIV/HPV Malignancies

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Abstract: Cervical cancer is the 4th most common cancer and cause of cancer-related death in women globally; in many lower-resource settings, especially sub-Saharan Africa (SSA), it is the most common. Virtually all cervical cancer and precancer are caused by high-risk human papillomavirus (hrHPV). HPV16 causes ~55- 60% and HPV18 causes ~10-15% of cervical cancer while the remaining ~12 HPV types cause the remaining 25-30% of cervical cancer. hrHPV, predominately HPV16, also causes most anal, vulvar, vaginal, and penile cancers and a significant proportion of oropharyngeal cancers. Prophylactic HPV vaccines have been developed and have shown to be nearly 100% protective against incident infection and related abnormalities against the target HPV types in the general population. However, the evidence for the effectiveness of prophylactic HPV vaccines in women living with human immunodeficiency virus (HIV) (WLWH) is less clear. HIV infection increases the risk of cervical cancer due to an impaired immune response to HPV. In 2011, Rwanda, a high-burden cervical cancer country in East Africa that has an HIV prevalence in adult women of 3.3%, implemented a national HPV vaccination program with Gardasil®, which protects against HPV16 and HPV18, the two HPV types that cause ~70% of cervical cancer, and HPV6 and HPV11, the two types that cause ~90% of anogenital warts (HPV6/11/16/18). Their program has achieved >90% coverage of the target population, primarily girls aged 12 years, annually. The implementation of a highly successful HPV vaccination program and the high prevalence of HIV, in addition to the research and medical capacity that Albert Einstein College of Medicine (Einstein) has helped to build at the Rwanda Military Hospital (RMH) and University of Rwanda (UR), makes Rwanda the ideal locale to study the long-term effects of HPV vaccination in WLWH. To answer questions about HPV vaccine effectiveness and immunity in Rwanda WLWH, collaborators at Einstein, RMH, and UR will conduct an observational study of WLWH and HIV-negative (HIV[-]) women who did (birth cohorts 1997 and later) and WLWH did not receive HPV vaccination (birth cohorts before 1997). We will compare the cervical, anal, and oral prevalent and 6-month persistent HPV6/11/16/18 infections in 757 HPV-vaccinated WLWH to those in 757 unvaccinated WLWH. We will also compare the HPV immune response in 548 HPV-vaccinated WLWH to 548 HPV-vaccinated HIV[-] women and the impact of switching from 3 doses to 2 doses of Gardasil in 2015. We also will validate a low-cost, simple point-of-care test for HPV16 antibodies as method to verify/determine HPV vaccination status. Finally, we will investigate the risk factors, including the cervicovaginal microbiome, for HPV persistence in WLWH. Our (long-term) goal is to establish a cohort of WLWH in whom we can examine the long-term effectiveness of HPV vaccination in WLWH now and in the future. This contribution is significant as it will establish the population effectiveness of HPV vaccination in WLWH living in SSA, the women at the highest risk of cervical cancer, for which there is a dearth of evidence. The proposed research is innovative as it leverages and expands the local research and medical capacity in Rwanda to examine one of the critically unanswered questions about HPV vaccine effectiveness in the context of the World Health Organization call for the global control of cervical cancer.