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

Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Protocols

https://clinicaltrials.gov/ct2/show/NCT03931083

Funding Statement

This work was supported by Swiss Cancer Research, grant number KFS-4156-02-2017, National Institute of Allergy and Infectious Diseases of the National Institutes of Health, grant number U01AI069924, and ESTHER Switzerland foundation, grant number 171222.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

National Health Research Authority of University of Zambia Biomedical Research Ethics Committee gave ethical approval for this work (ref: 014-09-18). The Zambia Medicines Regulatory Authority gave ethical approval for this work (ref: DMS/7/9/22/CT/084). The International Agency for Research on Cancer gave ethical approval for this work(IEC project number 18-15). Swissethics gave ethical approval for this work (ref: 2018-01399).

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Data Availability

The study protocol and statistical analysis plan are available upon request to the corresponding author. They can also be accessed on ClinicalTrials.gov (ref: NCT03931083). In accordance with FAIR principles, anonymised individual participant data or aggregate data will be made available upon reasonable request to the corresponding author (katayoun.taghavi@unibe.ch), and with approval from all investigators.

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