Diagnostic accuracy of cervical cancer screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among women living with HIV: A systematic review and meta-analysis.

Abstract

SummaryBackgroundWe systematically reviewed the diagnostic accuracy of cervical cancer screening and triage strategies in women living with HIV (WLHIV).MethodsCochrane Library, Embase, Global Health and Medline were searched for randomised controlled trials, prospective or cross-sectional studies published from database inception to 15 July 2022 reporting diagnostic accuracy of tests in cervical cancer screening and triage of screen-positive WLHIV. Studies were included if they reported the diagnostic accuracy of any cervical cancer screening or triage strategies for the detection of histologically-confirmed high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among WLHIV. Summary data were extracted from published reports. Authors were contacted for missing data where applicable. Sensitivity and specificity estimates for CIN2/3+ were pooled using models for meta-analysis of diagnostic accuracy data. Study quality was assessed using the QUADAS-2 tool for the quality assessment of diagnostic accuracy studies. PROSPERO registration:CRD42020189031.FindingsIn 38 studies among 18,737 WLHIV, the majority (n=19) were conducted in sub-Saharan Africa. The pooled prevalence was 12.0% (95%CI:9.8-14.1) for CIN2+ and 6.7% (95%CI:5.0-8.4) for CIN3+. The proportion of screen-positive ranged from 3-31% (visual inspection using acetic acid[VIA]); 2-46% (high-grade squamous intraepithelial lesions, and greater [HSIL+] cytology); 20-64% (high-risk[HR]-HPV DNA). In 14 studies, sensitivity and specificity of VIA were variable limiting the reliability of pooled estimates. In 5 studies where majority had histology-confirmed CIN2+, pooled sensitivity was 56.0% (95%CI:45.4-66.1; I2=65%) for CIN2+ and 65.0% (95%CI:52.9-75.4; I2=42%) for CIN3+; specificity for <CIN2 was 73.8% (95%CI:59.8-84.2, I2=94%). Cytology was similarly variable (sensitivity of ASCUS+ for CIN2+ range: 58-100%; specificity: 9-96%). In 28 studies, sensitivity of tests targeting 14-HR-HPV types was high (91.6%, 95%CI:88.1-94.1; I2=45% for CIN2+ and 92.5%, 95%CI:88.4-95.2; I2=32%) for CIN3+); but specificity for <CIN2 was low (62.2% (95%CI:57.9-66.4;I2=92%). Restriction to 8-HR-HPV increased specificity (65.8%; Relative specificity[RSpec] vs. 14-HR-HPV=1.17; 95%CI:1.10-1.24) with no significant change in sensitivity (CIN2+:85.5%; Relative Sensitivity[RSens]=0.94, 95%CI: 0.89-1.00; CIN3+:90%; RSens=0.96, 95%CI:0.89-1.03). VIA triage of 14-HR-HPV positive women decreased sensitivity for CIN2+ compared to HPV-DNA test alone (64.4% vs. 91.6%; RSens=0.68, 95%CI:0.62-0.75).InterpretationHPV-DNA based approaches consistently showed superior sensitivity for CIN2+/CIN3+ compared to VIA or cytology. The low specificity of HPV-DNA based methods targeting up to 14-HR-HPV could be improved significantly by restricting to 8-HR-HPV with only minor losses in sensitivity, limiting requirement for triage for which optimal approaches are less clear.FundingWorld Health Organisation; National Cancer Institute; European Union's Horizon 2020 and Marie Skłodowska-Curie Actions programme.