Cervical cancer screening is one of the most globally impactful cancer preventive measures and stands out due to its high degree of automation when primary HPV testing is used, which enables efficient and large-scale implementation but is lacking specificity. Therefore, effective triage and management of HPV-positive women is critical to avoid unnecessary colposcopy referrals and associated harms while maintaining high sensitivity for cervical precancer. Triage with p16/Ki-67 dual-stain (DS) testing has shown high sensitivity and specificity for detection of cervical precancers; however, its currently missing automation is hindering global implementation and adoption of the assay itself, in turn restricting the full potential of HPV-based cancer screeening. Dual-stain (DS) has already been included as an important component in the US Enduring Consensus Guidelines and the World Health Organization (WHO) cervical cancer screening guidelines as a recommended triage method for managing HPV-positive individuals. Compared with PAP cytology, dual-stain requires fewer subsequent colposcopies and detects more, and earlier, cervical intraepithelial neoplasia grade 3 or greater.
CYTOREADER™ Dual-Stain Cytology
CYTOREADER™™ is an AI-driven solution designed to assist with dual-stain cytology (p16/Ki-67). It utilizes a proprietary AI-based algorithm integrated into an automated laboratory and analysis process. The system is designed to support readers in detecting dual-stain events in high-throughput cervical cancer screening. It enables fast and efficient analysis of ThinPrep® or SurePath® liquid cytology slides stained with the CINtec PLUS® dual-stain assay by generating a gallery of 30 relevant image tiles based on computed likelihood for containing a dual-stain positive cell. This assists readers in evaluating cell samples more efficiently. The performance of CYTOREADER™ has been evaluated in externally conducted, blinded scientific studies, including research by the US National Cancer Institute. Please note that CYTOREADER™ is not FDA-approved and is intended for research use only or use in accordance with local regulatory requirements.
Components for using CYTOREADER comprise:
- Whole-Slide Scanning: Scanning: Scanning liquid cytology slides from ThinPrep® or Surepath™ with Whole-Slide Scanners (Hamamatsu Nanozoomer or Roche DP-Series).
- AI-Powered Cytoreader-V2: New Deep-Learning-Algorithm Cytoreader-V2 with exceptional robustness using a whole ensemble of different AI algorithms.
- Slide Management: Slide-Management server to store whole slides and manage the automatic slide workflow. Cases are offloaded from the system for archiving to external storage units.
- AI-Based Quality Control: Our suite of AI-based quality algorithms for fully automatic supervision of a successful ICC dual-stain staining pattern for each case under review, a high focus quality, and sufficient cellularity.
- Web-Based Review Station:The browser-based review station allowing extremely fast case evaluation based on the AI results. Case review can be performed locally or remotely from any geographical location.
- Scalable Deployment: The system is deployable locally or cloud-based and can be scaled nearly without limits on in-house or external IT GPU hardware.
*Cytoreader is not FDA or CE certified and is for research use only.
*The underlying AI technology is patent protected in the US (US 11,954,593 B2), European Union (IE20180171A) and China (CN112543934A).
Cytoreader-V2 Validation
Cytoreader-V2 was validated on 3,803 patients from the Kaiser Permanente Northern California (KPNC) Dual Stain Implementation Study (SurePathTM) [1], the NCI Biopsy Study (ThinPrep®) [2,3], the Improving Risk Informed HPV Screening study IRIS (SurePathTM) [4,5], the study STRIDES Studying Risk to Improve DisparitiES in Cervical Cancer in Mississippi (ThinPrep®) [6,5], and ACSS, the Anal Cancer Screening Study (ThinPrep®) [2,8]. Cytoreader-V2 has been evaluated to work with the Whole Slide Imaging (WSI) Scanners from Hamamatsu Photonics (Nanozoomer-Series) or Roche (DP-Series).
All Slide Types
Cytoreader-V2 has unique robustness as each image tile is evaluated by an ensemble of AI algorithms simultaneously and has been validated on the dual-stain assay CINtec+® from Roche and on liquid cytology slides prepared with ThinPrep® and SurePath™. It comprises a complex, barcode-automated workflow management. Also multiple AI algorithms automatically check in-parallel quality of all slides for focus quality, cellularity and staining failures. This way correct dual-stain immunochemistry is AI supervised. Cytotechnologists or pathologists can efficiently review cases in any web browser by displaying the 30 most likely dual-stain-containing tiles, facilitating a faster assessment of cell samples.
