Abstract
To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. MEDLINE and EMBASE were searched up to October 2020 for paired-design studies of cytology and testing for high-risk genotypes of human papillomavirus (hrHPV). The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, random-effects network meta-analysis of test accuracy, and GRADE rating. Twenty-seven prospective studies (185,269 subjects) were included. The combination of cytology (atypical squamous cells of undetermined significance or higher grades) and hrHPV testing (excepting genotyping for HPV 16 or 18 [HPV16/18]) with the either-positive criterion (OR rule) was the most sensitive/least specific, whereas the same combination with the both-positive criterion (AND rule) was the most specific/least sensitive. Compared with standalone cytology, non-HPV16/18 hrHPV assays were more sensitive/less specific. Two algorithms proposed for primary cytological testing or primary hrHPV testing were ranked in the middle as more sensitive/less specific than standalone cytology and the AND rule combinations but more specific/less sensitive than standalone hrHPV testing and the OR rule combination. Further research is needed to assess these results in population-relevant outcomes at the program level.
Highlights
To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis
Randomized controlled trials (RCTs) of well-screened populations have shown that strategies incorporating testing for high-risk human papillomavirus subtypes, which are the central etiological agents of cervical cancer pathogenesis[4], were, in aggregate, associated with a reduction in the invasive cancer incidence relative to that shown by cytological screening a lone[5]
Given the low incidence and mortality due to cervical cancer in high-income countries and the challenges associated with conducting de novo large and long-term randomized controlled trials (RCTs), decision modeling is an alternative realistic option to better understand the theoretical utility of the screening options[12]
Summary
To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. Given the low incidence and mortality due to cervical cancer in high-income countries and the challenges associated with conducting de novo large and long-term RCTs, decision modeling is an alternative realistic option to better understand the theoretical utility of the screening options[12] In this regard, comprehensive synthesis of the screening accuracy, a key model parameter of cytological and hrHPV testing and their available combination algorithms reported in rigorously conducted paired-design studies, is a valuable intermediate step. Recent meta-analyses have focused on either standalone cytological and/ or hrHPV testing[13,14,15] or a comparison of cytological testing with a specific combination algorithm not proposed in guidelines o nly[16] For those studies that assessed the diagnostic accuracy of selected and different pairs of tests of interest and their combination algorithms, network meta-analysis of diagnostic test accuracy studies is a useful approach that can compare all the assessed tests and combination algorithms in a single a nalysis[17]. We focused on the comparative accuracy of guideline-proposed combination algorithms by examining data derived from primary studies of healthy asymptomatic women that addressed verification bias because such bias is commonly observed in cancer screening accuracy studies
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