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.

Design: Systematic review and meta-analysis of diagnostic test accuracy studies.

Data sources: Systematic searches of multiple databases including Medline, Embase, and Scopus for studies published between January 1994 and June 2014.

Review 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.

Fig 1 Study flowchart of papers in selection process. *Gold standard performed in all women in the study population. †Gold standard performed in all women with a positive screening result and only a portion of women with a negative screening result. HC2=second generation hybrid capture assay; PICOS=population, intervention (screening tests), comparison (gold standard), outcomes (absolute and relative sensitivity and specificity, prevalence of CIN2+, and positivity rate of tests), study design; PCR=polymerase chain reaction; RCT=randomised controlled trial

Fig 2 Absolute sensitivity and specificity of VIA, VILI, and HPV testing for CIN2+ detection in sub-Saharan Africa. Diamond=95% confidence interval of the pooled measure computed with a bivariate random effects model. This figure includes only studies where the gold standard (colposcopy and colposcopy directed biopsies) was performed in all women of the study population (that is, GSA group). Heterogeneity across studies was assessed with Cochran’s Q test for each screening test (all P<0.05). DRC=Democratic Republic of Congo

Fig 3 Absolute accuracy of VIA, VILI and HPV testing for primary cervical cancer screening in sub-Saharan Africa. HSROC=hierarchical summary receiver operating characteristic regression curves. HSROC curves depict the fitted sensitivity as a function of specificity for VIA, VILI, HPV testing, and all three tests combined to detect CIN2+. These curves include only studies where gold standard (colposcopy and colposcopy directed biopsies) was applied to all women (that is, GSA group). Small blue squares, red circles, and green triangles and grey line circles=individual studies and 95% confidence ellipses; large blue squares, red circles, and green triangles and circles=pooled sensitivity and specificity and 95% confidence ellipses

Fig 4 Positive and negative predictive values of VIA, VILI, and HPV testing in detecting CIN2+ in sub-Saharan Africa. Curves=variation of positive and negative predictive values as a function of the prevalence of disease (CIN2+) using the Bayes’theorem, by screening test and by geographical region (western Africa, middle Africa, southern Africa, and eastern Africa). We considered the absolute sensitivity and specificity of each test to be constant and equal to the pooled values calculated with a random effects model. Prevalence of CIN2+ is shown on the x axis, and the resulting positive or negative predictive values are noted on the y axis. Heavy dotted curves=​​fitted predictive values; light dotted curves=95% confidence bands; NPV=negative predictive value; PPV=positive predictive value