Proof-of-principle study of a novel cervical screening and triage strategy: Computer-analyzed cytology to decide which HPV-positive women are likely to have ≥CIN2

Abstract

A challenge in implementation of sensitive HPV-based screening is limiting unnecessary referrals to colposcopic biopsy. We combined 2 commonly recommended triage methods: partial HPV typing and “reflex” cytology, evaluating the possibility of automated cytology. This investigation was based on 1,178 exfoliated cervical specimens collected during the enrollment phase of The Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED, Oklahoma City, Oklahoma). We chose a colposcopy clinic population to maximize number of outcomes, for this proof-of-principle cross-sectional study. Residual aliquots of PreservCyt were HPV-typed using Linear Array (LA, Roche Molecular Systems, Pleasanton, CA). High-risk HPV typing data and cytologic results (conventional and automated) were used jointly to predict risk of histologically defined ≥CIN2. We developed a novel computer algorithm that uses the same optical scanning features that are generated by the FocalPoint Slide Profiler (BD, Burlington, NC). We used the LASSO (Least Absolute Shrinkage and Selection Operator) method to build the prediction model based on a training dataset (n=600). In the validation set (n=578), for triage of all HPV-positive women, a cytologic threshold of ≥ASC-US had a sensitivity of 0.94, and specificity of 0.30, in this colposcopy clinic setting. When we chose a threshold for the severity score (generated by the computer algorithm) that had an equal specificity of 0.30, the sensitivity was 0.91. Automated cytology also matched ≥ASC-US when partial HPV typing was added to the triage strategy, and when we re-defined cases as ≥CIN3. If this strategy works in a prospective screening setting, a totally automated screening and triage technology might be possible.

Eurogin roadmap 2017: Triage strategies for the management of HPV‐positive women in cervical screening programs

“…Adequate recruitment, training and retention of cytology staff in an era of HPV primary screening may prove challenging and efforts to address this are required. A novel approach to automated cytology that achieves performance similar to expert manual evaluation may serve as mitigation to these challenges …”

“…A novel approach to automated cytology that achieves performance similar to expert manual evaluation may serve as mitigation to these challenges. 17…”

MicroRNAs as markers of progression in cervical cancer: a systematic review

“…Progression to invasion involves the accumulation of genetic errors. The overall process is complex and includes a number of genetic and epigenetic alterations [ 6 , 7 ].…”

Use of Automated Analysis of Cervical Cytology for the Detection of High-Grade Squamous Intraepithelial Lesions in Human Papillomavirus-Positive Women: A Future Practice?

“…2 Cytological abnormalities of LSIL or more severe. 3 Cytological abnormalities of HSIL or more severe.…”

“…A slide with a high severity-assigned score has a high probability of cellular abnormality, whereas a slide with a low severity-assigned score is more likely to be negative. Recently, in a proof-of-principle study, Schiffman et al [3] found that it is possible to triage HPV-positive women using the same screener (FocalPoint) with a redesigned algorithm.The above results are promising and indicate that automated cervical cytology screening could be an appropriate method by which to identify women at the highest risk of cancer precursor lesions among HPV-positive subjects. However, the decision regarding its introduction as a triage tool must be evaluated by additional clinical studies to estimate if this strategy is optimal for women in terms of benefits versus harms.…”