title: Performance of alternative strategies for primary cervical cancer screening in sub-Saharan Africa: systematic review and meta-analysis of diagnostic test accuracy studies.
abstract: OBJECTIVE
  To assess and compare the accuracy of visual inspection with acetic acid (VIA), visual inspection with Lugol's iodine (VILI), and human papillomavirus (HPV) testing as alternative standalone methods for primary cervical cancer screening in sub-Saharan Africa.
  
  
  METHODS
  Systematic review and meta-analysis of diagnostic test accuracy studies.
  
  
  METHODS
  Systematic searches of multiple databases including Medline, Embase, and Scopus for studies published between January 1994 and June 2014.
  
  
  METHODS
  Inclusion criteria for studies were: alternative methods to cytology used as a standalone test for primary screening; study population not at particular risk of cervical cancer (excluding studies focusing on HIV positive women or women with gynaecological symptoms); women screened by nurses; reference test (colposcopy and directed biopsies) performed at least in women with positive screening results. Two reviewers independently screened studies for eligibility and extracted data for inclusion, and evaluated study quality using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) checklist. Primary outcomes were absolute accuracy measures (sensitivity and specificity) of screening tests to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+).
  
  
  RESULTS
  15 studies of moderate quality were included (n=61,381 for VIA, n=46,435 for VILI, n=11,322 for HPV testing). Prevalence of CIN2+ did not vary by screening test and ranged from 2.3% (95% confidence interval 1.5% to 3.3%) in VILI studies to 4.9% (2.7% to 7.8%) in HPV testing studies. Positivity rates of VILI, VIA, and HPV testing were 16.5% (9.8% to 24.7%), 16.8% (11.0% to 23.6%), and 25.8% (17.4% to 35.3%), respectively. Pooled sensitivity was higher for VILI (95.1%; 90.1% to 97.7%) than VIA (82.4%; 76.3% to 87.3%) in studies where the reference test was performed in all women (P<0.001). Pooled specificity of VILI and VIA were similar (87.2% (78.1% to 92.8%) v 87.4% (77.1% to 93.4%); P=0.85). Pooled sensitivity and specificity were similar for HPV testing versus VIA (both P ≥ 0.23) and versus VILI (both P ≥ 0.16). Accuracy of VIA and VILI increased with sample size and time period.
  
  
  CONCLUSIONS
  For primary screening of cervical cancer in sub-Saharan Africa, VILI is a simple and affordable alternative to cytology that demonstrates higher sensitivity than VIA. Implementation studies are needed to assess the effect of these screening strategies on the incidence and outcomes of cervical cancer in the region.
authors.affiliation: Department of Gynecology and Obstetrics, Faculty of Medicine and Biomedical Sciences, University of Yaoundé, Yaoundé, Cameroon Division of Gynecology, Department of Gynecology and Obstetrics, Geneva University Hospitals, 1211 Geneva 14, Switzerland fokom.domgue@gmail.com.
authors.forename: Joël
authors.initials: J
authors.lastname: Fokom-Domgue
authors.affiliation: Division of Clinical Epidemiology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.affiliation: Division of Infectious and Chronic Diseases, Department of Internal Medicine, Yaoundé Central Hospital, Yaoundé, Cameroon.
authors.forename: Victoire
authors.initials: V
authors.lastname: Fokom-Defo
authors.affiliation: Department of Gynecology and Obstetrics, Faculty of Medicine and Biomedical Sciences, University of Yaoundé, Yaoundé, Cameroon.
authors.forename: Pierre Marie
authors.initials: PM
authors.lastname: Tebeu
authors.affiliation: Geneva Foundation for Medical Education and Research, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vassilakos
authors.affiliation: South African Medical Research Council and University of Cape Town, Cape Town, South Africa.
authors.forename: André Pascal
authors.initials: AP
authors.lastname: Kengne
authors.affiliation: Division of Gynecology, Department of Gynecology and Obstetrics, Geneva University Hospitals, 1211 Geneva 14, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Petignat
mesh_terms: D019342:Acetic Acid / Q000191:economics; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D004396:Coloring Agents / Q000191:economics; D003362:Cost-Benefit Analysis; D055088:Early Detection of Cancer / Q000191:economics / Q000379:methods*; D005260:Female; D006801:Humans; D007454:Iodides / Q000191:economics; D008403:Mass Screening / Q000191:economics / Q000379:methods*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000191:economics; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000191:economics / Q000821:virology; D014626:Vaginal Smears / Q000191:economics; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000191:economics / Q000821:virology
chemical_list: D004396:Coloring Agents; D007454:Iodides; D019342:Acetic Acid; C010389:Lugol's solution