title: A spectral phenotype of oncogenic human papillomavirus-infected exfoliative cervical cytology distinguishes women based on age.
abstract: BACKGROUND
  Human papillomavirus (HPV) is a sexually-transmitted infection associated with cervical cancer. Of over 100 HPV types identified, 13 are high-risk oncogenic. In unvaccinated women worldwide, the incidence of cervical cancer from HPV16 and HPV18 will remain. Cervical cytology can be graded from normal (atypia-free) to low-grade to high-grade. Infrared (IR) spectroscopy is a non-destructive technique that allows the acquisition of a biochemical-cell fingerprint based on vibrational states of chemical bonds.
  
  
  METHODS
  Exfoliative cervical cytology specimens (n=147) were retrieved, graded by a cytologist and HPV-tested/genotyped using hybrid capture 2 and the Roche HPV Linear Array. Additionally, the spectral signatures of cervical cell lines C33A, HeLa and SiHa were examined. After washing, cellular material was transferred to low-E glass slides and interrogated using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. Given the complex nature of the dataset consisting of thousands of variables (wavenumbers), we used multivariate analysis for data reduction and information retrieval. Principal component analysis coupled with linear discriminant analysis (PCA-LDA) generated a visual representation of the data (scores plot) and, identification of the wavenumbers and consequent biochemical entities responsible for segregation (loadings plot).
  
  
  RESULTS
  Immortalised cell lines were readily distinguishable from each other. It was difficult to segregate categories of cytology associated with HPV infection types. However, in low-grade cytology infected with high-risk oncogenic HPV16 or HPV18, it was possible to segregate women based on whether they were aged 20-29years vs. 30-39years.
  
  
  CONCLUSIONS
  Our findings suggest a spectral phenotype in exfoliative cervical cytology associated with transient vs. persistent HPV infection.
authors.affiliation: Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK.
authors.forename: Jemma G
authors.initials: JG
authors.lastname: Kelly
authors.forename: Karen T
authors.initials: KT
authors.lastname: Cheung
authors.forename: Cara
authors.initials: C
authors.lastname: Martin
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Leary
authors.forename: Walter
authors.initials: W
authors.lastname: Prendiville
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Martin-Hirsch
authors.forename: Francis L
authors.initials: FL
authors.lastname: Martin
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D016002:Discriminant Analysis; D005260:Female; D052162:Human papillomavirus 16 / Q000502:physiology*; D052161:Human papillomavirus 18 / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D025341:Principal Component Analysis; D017550:Spectroscopy, Fourier Transform Infrared; D055815:Young Adult