A virtual microscopy system to scan, evaluate and archive biomarker enhanced cervical cytology slides

Cell Oncol. 2010;32(1-2):109-19. doi: 10.3233/CLO-2009-0508.


Background: Although cytological screening for cervical precancers has led to a reduction of cervical cancer incidence worldwide it is a subjective and variable method with low single-test sensitivity. New biomarkers like p16 that specifically highlight abnormal cervical cells can improve cytology performance. Virtual microscopy offers an ideal platform for assisted evaluation and archiving of biomarker-stained slides.

Methods: We first performed a quantitative analysis of p16-stained slides digitized with the Hamamatsu NDP slide scanner. From the results an automated algorithm was created to reliably detect cells, nuclei and p16-stained cells. The algorithm's performance was evaluated on two complete slides and tiles from 52 independent slides (11,628, 4094 and 25,619 cells/clusters, respectively).

Results: We achieved excellent performance to discriminate unstained cells from nuclei and biomarker-stained cells. The automated algorithm showed a high overall and positive agreement (99.0-99.7% and 70.9-83.4%, respectively) with the gold standard and had a very high sensitivity (89.1-100.0%) and specificity (98.9-100.0%) to detect biomarker-stained cells.

Conclusion: We implemented a virtual microscopy system allowing highly efficient automated prescreening and archiving of biomarker-stained slides. Based on the initial results, we will evaluate the performance of our system in large epidemiologic studies against disease endpoints.

Publication types

  • Evaluation Study

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Cytological Techniques / methods*
  • Early Detection of Cancer / methods
  • Female
  • Humans
  • Photomicrography / methods*
  • Uterine Cervical Neoplasms / chemistry*
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / pathology


  • Biomarkers, Tumor