Grant: Ca. Gr.: Biomedical Res. for HIV/AIDS/STBBI -Next-gen. therapeutic interventions

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI). It is estimated that 80% of sexually active individuals will be infected at least once in their lifetime. While HPV vaccination is highly efficient in preventing HPV infection, worldwide uptake remains under the WHO target, with low availability in Africa. Therefore, cervical cancer remains the second most common cancer in women, and most of them occur in low- and middle-income countries (85%), where it represents close to 12% of all female cancer. Most of the cervical cancer cases observed worldwide are in Sub-Saharan Africa. Therefore, it is essential to develop new therapeutic tools to improve virus clearance and prevent HPV-related cancer. Aging as a woman comes with changes in sex hormone expression that affect the immune response and inflammation. These changes are associated with a second peak in HPV incidence and a higher risk of HPV persistence. Here, we propose to repurpose aspirin to target vaginal inflammation and improve the rate of HPV clearance in older female sex workers (FSWs) infected with HPV from Nairobi, Kenya. Aspirin is an anti-inflammatory that is widely available, affordable and has a safe track record. We will follow 300 older FSWs infected with HPV for a year and determine the rate of HPV clearance. Participants will be randomized to take low-dose aspirin or nothing. In a subgroup (50 per study arm), we will determine the impact of aspirin on the genital microbiome, immune response, and blood memory response to HPV. While aging is associated with hormonal, little is known about how it affects the host's immune response to mucosal pathogens. This study will provide data to determine whether aspirin decreases genital inflammation in the context of HPV infection and improves the rate of HPV clearance in older women. It could provide a new therapeutic tool to prevent cervical cancer in those who did not access the HPV preventive vaccine.