Comparison of the ScreenFire and Xpert HPV assays for the detection of human papillomavirus and cervical precancer among women living with HIV in Malawi.

Background: The World Health Organization (WHO) recommends human papillomavirus (HPV) testing for primary cervical cancer screening, including among women living with HIV (WLWH). Low-and-middle-income countries (LMICs) account for 85% of the cervical cancer burden globally, yet have limited access to HPV-based screening, largely due to cost. This study aims to compare the performance of a rapid, isothermal amplification HPV assay (ScreenFire) to that of the Xpert HPV assay for the detection of HPV and cervical precancer among WLWH in Malawi.

Methods: We utilized stored self- and provider-collected specimens from a prospective cohort study of WLWH in Malawi from July 2020 to February 2022. Specimens were tested with both Xpert and ScreenFire HPV assays. The overall and within-channel non-hierarchical agreement between ScreenFire and Xpert was determined for both self- and provider-collected specimens. Hierarchical ScreenFire HPV positivity by channel was compared to Xpert for each histological diagnosis - cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to
Results: 315 matched self- and provider-collected specimens had valid results from both Xpert and ScreenFire testing and were included in analyses. Of these, 245 (78%) had normal pathology, 21 CIN1 (7%), 14 CIN2 (4%), and 35 CIN3 (11%). Among provider-collected specimens, the assays had 80% agreement on overall HPV positivity (unweighted kappa 0.59, 95% 0.50-0.69). ScreenFire was HPV-positive in 90% of self-collected specimens that were HPV-positive on Xpert. Channel agreement between the assays was high for both self- and provider-collected specimens, but slightly lower for HPV18/45. In hierarchical analysis, ScreenFire demonstrated high concordance with Xpert testing for detecting CIN2+ cases in all channels, missing no HPV 16 or HPV 18/45 positive CIN2+ case that was positive on Xpert, in both self- and provider-collected specimens.

Conclusion: In this study of stored specimens, the ScreenFire HPV assay performed well in the detection of HPV and CIN2+ among WLWH compared to the Xpert HPV assay. If supported by larger validation studies, ScreenFire could be an affordable alternative point-of-care HPV assay for use in LMICs.