Abstract
The World Health Organization recommends human papillomavirus (HPV) testing for cervical screening. Extended genotyping can identify the highest-risk HPV-positive women. An inexpensive, rapid, mobile isothermal amplification assay (ScreenFire HPV RS test) was recently redesigned to yield four channels ordered by cancer risk (ie, hierarchical approach): HPV16, HPV18/45, HPV31/33/35/52/58 and HPV39/51/56/59/68. Stored specimens from 2076 women (mean age 30.9) enrolled in a colposcopy clinic, with high HPV prevalence, were tested with ScreenFire. We calculated hierarchical channel positivity and non-hierarchical channel and type positivity, according to histologic diagnosis (256 cancer, 350 cervical intraepithelial neoplasia [CIN]3, 409 CIN2, 1020 < CIN2) and known virologic reference results (Linear Array and TypeSeq). Additionally, we analyzed ScreenFire time-to-positive up to 60 min by channel and histology. Overall clinical sensitivity for CIN3+ was 94.7% (95% confidence interval 92.6-96.4), similar to Linear Array (92.3, 89.7-94.3) and TypeSeq (96.0, 93.9-97.6). Sensitivity was high for all types and channels. The hierarchical approach was well in line with HPV typing and histologic diagnosis, prioritizing higher risk women having HPV16 and precancer. For HPV16, time-to-positive was shorter in women with precancer. ScreenFire showed excellent agreement with research reference typing tests and detection of CIN2+. Risk-based type results could help guide clinical management of HPV-positive women. Time-to-positive combined with genotyping might be useful. ScreenFire is rapid, mobile, relatively inexpensive and designed for implementation of HPV-based screening and management, including in lower-resource settings. Further validation in screening by self-sampling and practical effectiveness merit evaluation.