Timothy Wilkin1, Huichao Chen2, Vikrant Sahasrabuddhe3, Roy Matining2, Rosie Mngqibisa4, Lameck Chinula5, Yamikani Mbilizi6, Tsitsi Magure7, Ayotunde E Omoz-Oarhe8, Mohammed Rassool9, Cynthia Riviere10, Rhamesh Bhosale11, Sheela Godbole12, Reena Naranjo13, Robert Coombs14, Pamela Michelow15, Catherine Godfrey16, Cynthia Firnhaber17. 1. Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA. 2. Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA. 3. Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland, USA. 4. Durban International Clinical Research Site, Enhancing care Foundation, King Edward Hospital, Durban, South Africa. 5. University of North Carolina Project-Malawi, Lilongwe, Malawi. 6. Johns Hopkins Research Project, Blantyre, Malawi. 7. University of Zimbabwe Faculty of Medicine and Health Sciences, Harare, Zimbabwe. 8. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. 9. Clinical HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa. 10. Clinical Research Department, Les Centres GHESKIO, Port-au-Prince, Haiti. 11. Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India. 12. Division of Epidemiology, ICMR-National AIDS Research Unit, Pune, India. 13. Public Health & Scientific Research, Social & Scientific Systems, Inc, A DLH Holdings Company, Silver Spring, Maryland, USA. 14. Departments of Laboratory Medicine & Pathology and Medicine, University of Washington, Seattle, Washington, USA. 15. National Health Laboratory Service, Johannesburg, South Africa. 16. Office of the Global AIDS Coordinator, Department of State, Washington D.C., USA. 17. Division of Infectious Disease, Department of Medicine, University of Colorado Medical School, Aurora, Colorado, USA.
Abstract
BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.
BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.
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