Abstract Current estimates indicate that every year 5,250 women (crude rate 20.5) are diagnosed with cervical cancer in Kenya and 3,286 (crude rate 12.8) die from the disease. Cervical cancer ranks as the 2nd most frequent cancer among women in Kenya and the 1st most frequent cancer among women between 15-44 years of age. About 9.1% of women in the general population are estimated to harbor human papillomavirus (HPV) 16/18 and 63.1% of invasive cervical cancers are attributed to HPV 16/18. In Uganda, cervical cancer is the number one cause of cancer related death in women. 6,413 Ugandan women (crude rate 28.8) are diagnosed with cervical cancer and 4,301(crude rate 19.3) die from the disease. About 3.6% of the general population harbor HPV 16/18 and 57% of invasive cancer is attributable to HPV 16/18. HIV-infected women have higher prevalence, incidence, and persistence of HPV infections, more so in women with severe immune compromise. HIV has been shown to increase the risk of the development, progression and recurrence of cervical intraepithelial neoplasia. Several studies have consistently shown that HIV-infected women present higher risk of CIN persistence or recurrence after standard therapy . Both Kenya and Uganda have high prevalence for HIV/AIDS at 7% and 12.9%, respectively. In settings where loop electrosurgical excision procedure (LEEP) is available, accessible and appropriate, treatment with LEEP is recommended by the WHO. However, there is a paucity of studies assessing the efficacy of LEEP among HIV-infected women and the characteristics of CIN2/3 lesions after LEEP. The core objective of this application is to understand the natural history of recurrent CIN2/3 lesions among HIV-infected women after LEEP. To help guide management based on HIV/HPV science, we propose an epidemiologic and immunohistochemical study of the cervix following LEEP to address the value of destruction of the cervical transformation zone to prevent cancer. We propose to enroll 300 HIV-infected women with CIN2/3 undergoing LEEP and follow them every 6 months for 2 years with colposcopy and biopsy when appropriate. We will do a repeat LEEP for recurrent CIN2/3 lesions. The Specific Aims for this proposed study are: 1. To assess the incidence and risk factors for “recurrent” CIN2/3 after LEEP among HIV- infected women. 2. To determine baseline HR-HPV types (in tissue) among HIV-infected women with CIN2/3 undergoing LEEP compared to the HR-HPV types with “recurrent” cervical lesions after a second LEEP. 3. To determine the immunohistochemical differences between the initial and repeat LEEP specimens among HIV-infected women with “recurrent” CIN2/3

Narrative HIV-infected women have a higher risk of persistent high-risk HPV infection leading to higher rates of cervical intraepithelial neoplasia (CIN) 2/3. The standard of care for CIN2/3 is loop electrosurgical excision procedure (LEEP). However, there is a gap in our understanding of recurrent CIN 2/3. This study proposes to increase our understanding of recurrent CIN2/3 in order to decide the best treatment for this recurrence.