Protocol for the study of cervical cancer screening technologies in HIV-infected women living in Rwanda

• Published in: BMJ open 2018-08, Vol.8 (8), p.e020432-e020432
• Main Authors: Murenzi, Gad, Dusingize, Jean-Claude, Rurangwa, Theogene, Sinayobye, Jean d’Amour, Munyaneza, Athanase, Murangwa, Anthere, Zawadi, Thierry, Hebert, Tiffany, Mugenzi, Pacifique, Adedimeji, Adebola, Mutesa, Leon, Anastos, Kathryn, Castle, Philip E
• Format: Article
• Language: English
• Subjects: Adult; Bioinformatics; Biopsy; Cellular biology; Cervical cancer; Clinical Protocols; Colposcopy; Cross-Sectional Studies; Deoxyribonucleic acid; DNA; DNA methylation; DNA, Viral - genetics; Early Detection of Cancer - methods; Female; Genomes; Genotype; Global Health; HIV; HIV Infections - epidemiology; Human immunodeficiency virus; Human papillomavirus; Humans; Infections; Medical screening; Middle Aged; Mortality; Oncogene Proteins, Viral - genetics; Papillomaviridae - genetics; Papillomavirus Infections - diagnosis; Research Design; Rwanda - epidemiology; Sampling Studies; Uterine Cervical Dysplasia - diagnosis; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - virology; Vaginal Smears; Womens health
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2017-020432

IntroductionThe optimal method(s) for screening HIV-infected women, especially for those living in sub-Saharan Africa, for cervical precancer and early cancer has yet to be established.Methods and analysisA convenience sample of >5000 Rwandan women, ages 30–54 years and living with HIV infection, is being consented and enroled into a cross-sectional study of cervical cancer screening strategies. Participants are completing an administered short risk factor questionnaire and being screened for high-risk human papillomavirus (hrHPV) using the Xpert HPV assay (Cepheid, Sunnyvale, California, USA), unaided visual inspection after acetic acid (VIA) and aided VIA using the Enhanced Visual Assessment (EVA) system (Mobile ODT, Tel Aviv, Israel). Women positive for hrHPV and/or by unaided VIA undergo colposcopy, which includes the collection of two cervical specimens prior to undergoing a four-quadrant microbiopsy protocol. The colposcopy-collected specimens are being tested by dual immunocytochemical staining for p16INK4a and Ki-67 (CINtec PLUS Cytology, Ventana, Tucson, Arizona, USA) and for E6 or E7 oncoprotein for 8 hrHPV genotypes (HPV16, 18, 31, 33, 35, 45, 52 and 58) using the next-generation AV Avantage hrHPV E6/E7 test (Arbor Vita Corporation, Freemont, California, USA). Women with a local pathology diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) or pathology review diagnosis of CIN grade three or more severe (CIN3+) will receive treatment. Clinical performance and cost-effectiveness (eg, sensitivity, specificity and predictive values) of different screening strategies and algorithms will be evaluated.Ethics and disseminationThe protocol was approved by local and institutional review boards for human subjects research. At the completion of the study, results will be disseminated to the scientific community through peer-reviewed publication and to the Rwandan stakeholders through an external advisory panel.