Performance of screening tools for cervical neoplasia among women in low- and middle-income countries: A systematic review and meta-analysis

Abstract

Objective To evaluate the performance of visual inspection with acetic acid (VIA) testing, visual inspection with Lugol’s iodine (VILI), primary HPV testing, and conventional Pap smear in detecting CIN2+ among non-pregnant women aged 30–65 in LMICs between 1990 and 2020. Design Systematic review and meta-analysis. Setting and participants Low- and middle-income countries, non-pregnant women aged 30–65. Methods CENTRAL (Cochrane Library), CINAHL, Embase, Global Health, PubMed, and Web of Science databases were systematically searched to identify studies evaluating the performance of cervical cancer screening methods in LMICs. A diagnostic test accuracy meta-analysis was conducted to evaluate the performance of 4 screening methods in detecting CIN2+ relative to biopsy or cytology reference standards. Pooled statistics for sensitivity, specificity, diagnostic odds ratios, and summary receiver operating characteristic curves were determined for each method. Subgroup analyses were performed to examine whether there was variation in performance based on different reference standards for defining CIN2+, specifically: colposcopy-directed biopsy, biopsy alone, colposcopy alone, or liquid-based cytology. Results Eighteen studies were identified through systematic review. Twelve studies were included in meta-analysis; 11 were cross-sectional and 1 was a randomized controlled clinical trial. The remaining six of the eighteen studies were inclided in a narrative syntehsis. Pooled estimates for sensitivity for VIA, VILI, primary HPV testing, and conventional Pap smear were 72.3%, 64.5%, 79.5%, and 60.2%, respectively; pooled estimates for specificity were 74.5%, 68.5%, 72.6%, and 97.4%, respectively; the diagnostic odds ratios were 7.31, 3.73, 10.42, 69.48, respectively; and the area under the summary receiver operating characteristic curves were 0.766, 0.647, 0.959, and 0.818, respectively. Performance of the screening method varied based on the reference standard used; pooled estimates using either colposcopy-directed biopsy or biopsy alone as the reference standard generally reported lower estimates; pooled estimates using either colposcopy alone or liquid-based cytology as references reported higher estimates. Conclusions and implications This meta-analysis found primary HPV testing to be the highest performing cervical cancer screening method in accurately identifying or excluding CIN2+. Further evaluation of performance at different CIN thresholds is warranted.

Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia

“…Studies in which the reference standard is obtained only from visible lesions during colposcopy 24,25 have higher estimates of sensitivity and specificity than when all women have biopsies. 6,26,27 We also found a prevalence of pre-cancer among WLHIV that was higher than in another Zambian study, in which CIN2+ prevalence was 16% among 200 women screened at the University Teaching Hospital in 2016. 8 A systematic review evaluating diagnostic accuracy of cervical cancer screening strategies among WLHIV found a pooled prevalence of 12% (range 2-26%), 9 with higher prevalence in tertiary settings where referral for abnormal cervical smear or positive HPV test suggested a high risk for CIN2+.…”

“…The sensitivity of testing for hrHPV was lower in our study than in many others. 6,7 In contrast to many previous studies, we took four biopsies from women with no visible lesions and repeated testing six months later to avoid partial verification bias when only acetowhite lesions are sampled. We found the sensitivity of hrHPV was 65.3% (95% CI: 59.4-70.7) when biopsies were obtained from all women and 85.7% (95% CI: 73.3-92.9) if only biopsies from visible lesions were considered.…”

“…Our reference standard methods, taking two to four biopsies at two timepoints, might have detected more CIN2+ cases than in studies taking one biopsy from the most severe cervical lesion 28,29 or a maximum of two biopsies. 6,7 Wentzensen et al found that sensitivities for detecting CIN2+ increased from 61% (95% CI: 55-67) in a single biopsy to 86% (95% CI: 80-90) with two biopsies to 96% (95% CI: 91-99) with three biopsies. 29 In contrast to previous studies that calculated combined test accuracy using the denominator of women testing positive from the first test, we considered all women in our denominator so as not to miss any disease in the target population.…”

“…An evaluation of alternative same-day screening tests among WLHIV, using methods that minimise verification biases, has not yet been conducted. 1,6,7 Colposcopy is the cornerstone of visual assessment for cervical cancer screening, used in screening pathways of high-resource countries but is rarely accessible in low-resource settings where most WLHIV live. In low-resource settings, visual inspection with acetic acid (VIA) is commonly used, 5,6 but with low accuracy, particularly for WLHIV.…”

“…1,6,7 Colposcopy is the cornerstone of visual assessment for cervical cancer screening, used in screening pathways of high-resource countries but is rarely accessible in low-resource settings where most WLHIV live. In low-resource settings, visual inspection with acetic acid (VIA) is commonly used, 5,6 but with low accuracy, particularly for WLHIV. 7,8 The WHO strategy recommends molecular tests to detect hrHPV, which were reported to have a sensitivity of 91.6% (95% CI 88.1-94.1) among WLHIV in a systematic review.…”