Grant: Team Grant: Bringing Biology to Cancer Prevention - Cancer in Women

The Human Papilloma Virus (HPV) causes cervical cancer in women. Although all women age into menopause, little is known about the effect of the menopausal hormonal changes on the immune system. We have shown that postmenopausal women have changes in their immune responses resulting in increased levels of inflammation at the female genital tract. This is concerning because inflammation is known to cause persistence of HPV which causes cervical cancer. The risk of women developing cervical cancer increases greatly following menopause. This proposal will assess changes in the immune system, sex hormones and HPV expression as women age into menopause. We will also test if we can reduce the levels of inflammation in postmenopausal women and if this is associated with clearance of their HPV infection. We will work with a cohort of female sex workers from the Sex Worker Outreach Program (SWOP) from Nairobi, Kenya, whom we have collaborated with since 1984. The women of SWOP have identified healthy aging and cervical cancer as research priorities, which this proposal addresses. We will test two safe and community-acceptable interventions to see if they can reduce inflammation in postmenopausal women. First is the anti-inflammatory drug acetylsalicylic acid (ASA or aspirin). Our group has conducted studies with SWOP which have demonstrated that taking ASA is safe and reduces inflammation at the genital tract. The second is hormone replacement therapy (HRT), a vaginal estrogen cream, which is commonly used to treat symptoms of menopause and is known to decrease inflammation. By testing ASA, estrogen-therapy or no treatment groups, we will determine if these interventions can reduce markers of inflammation and if that results in the clearance of the HPV infections. Our goal is to determine if, as women age into menopause, they can receive a treatment that reduces the risk of them being persistently infected with a virus that causes cervical cancer.