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.

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

Introduction: To provide evidence to improve cervical screening for women living with HIV (WLHIV), we assessed the accuracy of screening tests that can be used in low-resource settings and give results at the same visit. Methods: We conducted a paired, prospective study among consecutive eligible WLHIV, aged 18 to 65 years, receiving cervical cancer screening at one hospital in Lusaka, Zambia. The histopathological reference standard was multiple biopsies taken at two time points. The target condition was high-grade cervical intraepithelial neoplasia (CIN2+). The index tests were high-risk human papillomavirus detection (hrHPV, Xpert HPV, Cepheid), portable colposcopy (Gynocular, Gynius), and visual inspection with acetic acid (VIA). Accuracy of stand-alone and test combinations were calculated as the point estimate with 95% confidence intervals. A sensitivity analysis considered disease when only visible lesions were biopsied. Results: Among 371 participants with histopathological results, 27% (101/371) women had CIN2+ and 23% (23/101) was not detected by any index test. Sensitivity and specificity for stand-alone tests were: hrHPV, 67.3% (95% CI: 57.7 to 75.7) and 65.3% (59.4 to 70.7); Gynocular 51.5% (41.9 to 61.0) and 80.0% (74.8 to 84.3); and VIA 22.8% (15.7 to 31.9) and 92.6% (88.8 to 95.2), respectively. The combination of hrHPV testing followed by Gynocular had the best balance of sensitivity (42.6% [33.4 to 52.3]) and specificity (89.6% [85.3 to 92.7]). All test accuracies improved in sensitivity analysis. Conclusion: The low accuracy of screening tests assessed might be explained by our reference standard, which reduced verification and misclassification biases. Better screening strategies for WLHIV in low-resource settings are urgently needed.

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

Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing. Atila AmpFire® HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert® HPV assay in detection of both HPV and clinically significant cervical disease.We utilized stored cervical specimens from a prospective cohort study of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia.63 stored cervical specimens had detectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI 76.3-98.1) and negative percent agreement was 79.3% (95% CI 60.3-92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n = 2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia.The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs. 

/pdf/comparison-of-the-ampfire-r-multiplex-hpv-assay-to-the-xpert-1q6qdw9z.pdf

Comparison of the AmpFire® Multiplex HPV Assay to the Xpert® HPV Assay for detection of human papillomavirus and cervical disease in women with human immunodeficiency virus: a pragmatic performance evaluation

Previous studies reported human immunodeficiency virus (HIV) could enhance human papillomavirus (HPV)‐induced cervical cancer. Therefore, the burden of cervical cancer associated with HIV across different regions and time periods need to be assessed. We aim to investigate the global burden of cervical cancer associated with HIV infection. Age standardized rates (ASRs) of cervical cancer disability‐adjusted life‐years (DALYs) in females (≥15 years old) were calculated by standardization, according the age‐specific DALYs numbers extracted from GBD data set 2019. Population attributable fractions was calculated by combining the published risk ratio, with the HIV prevalence (≥15 years old) from Joint United Nations Programme on HIV and AIDS (UNAIDS), and transferred to estimate the HIV‐associated cervical cancer burden. Expected annual percentage changes (EAPCs) was calculated to describe the temporal trend of ASR from 1990 to 2019. Pearson correlation analysis were conducted to assess the correlation between the ASR or EAPCs and the socio‐demographic index. The worldwide DALYs ASR caused by HIV‐associated cervical cancer rose from 3.78 (95% confidence interval [CI]: 2.19–5.56) in 1990 to 9.50 (95% CI: 5.66–13.79) in 2019 per 100k population. In 2019, the region with the greatest burden was Eastern and Southern Africa, with the highest DALYs of 273 900 (95% CI: 149 100–476 400) and ASR of 254.44 per 100k population (95% CI: 168.86–329.28). Notably, the Eastern Europe and Central Asia regions had the highest EAPC (14.07%) of HIV‐associated DALYs ASR. Women in Eastern and Southern Africa experience the greatest burden of HIV‐associated cervical cancer, while the Eastern Europe and Central Asia regions had witnessed the largest increase over the last 30 years. Prioritize the promotion of HPV vaccination and cervical cancer screening for women living with HIV were crucial in these regions.

Global and regional estimates of cervical cancer burden associated with human immunodeficiency virus infection from 1990 to 2019

Background: Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing.Atila AmpFire HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert HPV assay in detection of both HPV and clinically significant cervical disease. Methods: We utilized stored cervical specimens from a prospective cohortstudy of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia. Results : 63 stored cervical specimens haddetectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI: 76.3-98.1) and negative percent agreement was 79.3% (95% CI: 60.3-92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n=2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia. Conclusions : The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs. 

/pdf/comparison-of-the-ampfire-r-multiplex-hpv-assay-to-the-xpert-rt1k9mgy.pdf

Comparison of the AmpFire® Multiplex HPV Assay to the Xpert® HPV Assay for detection of human papillomavirus and cervical disease in women with human immunodeficiency virus: A pragmatic performance evaluation

http://www.thelancet.com/article/S2589537022003753/pdf

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

Michael Chung

Papers

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