title: Towards early detection of cervical cancer: Fractal dimension of AFM images of human cervical epithelial cells at different stages of progression to cancer.
abstract: We used AFM HarmoniX modality to analyse the surface of individual human cervical epithelial cells at three stages of progression to cancer, normal, immortal (pre-malignant) and carcinoma cells. Primary cells from 6 normal strains, 6 cancer, and 6 immortalized lines (derived by plasmid DNA-HPV-16 transfection of cells from 6 healthy individuals) were tested. This cell model allowed for good control of the cell phenotype down to the single cell level, which is impractical to attain in clinical screening tests (ex-vivo). AFM maps of physical (nonspecific) adhesion are collected on fixed dried cells. We show that a surface parameter called fractal dimension can be used to segregate normal from both immortal pre-malignant and malignant cells with sensitivity and specificity of more than 99%. The reported method of analysis can be directly applied to cells collected in liquid cytology screening tests and identified as abnormal with regular optical methods to increase sensitivity.
  
  
  BACKGROUND
  Despite cervical smear screening, sometimes it is very difficult to differentiate cancers cells from pre-malignant cells. By using AFM to analyze the surface properties of human cervical epithelial cells, the authors were able to accurately identify normal from abnormal cells. This method could augment existing protocols to increase diagnostic accuracy.
authors.affiliation: Department of Physics, Clarkson University, Potsdam, NY, USA.
authors.forename: Nataliia V
authors.initials: NV
authors.lastname: Guz
authors.affiliation: Department of Mechanical Engineering, Tufts University, Medford, MA, USA.
authors.forename: Maxim E
authors.initials: ME
authors.lastname: Dokukin
authors.affiliation: Department of Biology, Clarkson University, Potsdam, NY, USA.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Woodworth
authors.affiliation: Department of Physics, Clarkson University, Potsdam, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cardin
authors.affiliation: Department of Mechanical Engineering, Tufts University, Medford, MA, USA; Department of Biomedical Engineering, Tufts University, Medford, MA, USA; Department of Physics, Tufts University, Medford, MA, USA. Electronic address: igor.sokolov@tufts.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Sokolov
mesh_terms: D045744:Cell Line, Tumor; D018450:Disease Progression; D055088:Early Detection of Cancer; D004847:Epithelial Cells / Q000473:pathology / Q000648:ultrastructure*; D005260:Female; D017709:Fractals; D052162:Human papillomavirus 16 / Q000472:pathogenicity; D006801:Humans; D018625:Microscopy, Atomic Force; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000648:ultrastructure
keywords: Atomic force microscopy; Cervical cancer; Early cancer detection; Novel detection methods; Pap smear/liquid cytology tests