title: 5-aminolevulinic-acid-based fluorescence spectroscopy and conventional colposcopy for in vivo detection of cervical pre-malignancy.
abstract: BACKGROUND
  Sensitized fluorescence diagnostics are based on selective accumulation of photosensitizer in the tissue where carcinogenesis has started. The present study compared topical 5-aminolevulinic acid (5-ALA)-based fluorescence spectroscopy (FS) in vivo with conventional colposcopy for cervical intraepithelial neoplasia (CIN) detection.
  
  
  METHODS
  We enrolled 48 patients who were referred for colposcopy because of high-grade changes in cervical cytology. Every inspected cervix was divided in to quadrants, and there were 174 quadrants included in the study. Each patient had a cytological smear, colposcopy, FS and histopathological analysis. For FS, 3% 5-ALA cream was used topically and after an average 135 min incubation, fluorescence spectra were recorded from the cervix in vivo. FS and colposcopy results were correlated with histopathology.
  
  
  RESULTS
  All spectra were evaluated by a ratio of the protoporphyrin IX fluorescence intensity at 634 nm and autofluorescence intensity at 510 nm. For proper grouping of low-risk and high-risk cases, a threshold of 3.87 was calculated. Data per quadrant showed that FS had higher sensitivity than colposcopy (71.7% vs 67.4%) but specificity was greater for colposcopy (86.6% vs 75.6%). Combination of the methods showed higher sensitivity (88.0% vs 67.4%) but reduced specificity (88.0% and 69.5%), but it had the highest number of correctly identified high-risk changes and the highest (79.3%) accuracy. Data for each patient showed FS sensitivity of 91.2%, which was greater than for colposcopy (88.2%). Higher overdiagnosis resulted in decreased specificity for fluorescence methodology-71.4% versus 78.6% for colposcopy. In both cases, accuracy was 85.4% and effectiveness was >80%, which means that both methods can be used to determine high-risk cervical intraepithelial neoplasia. The diagnostic sensitivity of 97.1% for this complementary diagnosis indicates that it could be the best choice for detection of high-risk changes.
  
  
  CONCLUSIONS
  5-ALA-based FS is an objective method, requiring short-term administration for appropriate fluorescence measurements. FS is a promising diagnostic tool with similar accuracy as colposcopy but with the potential advantage of providing objective results.
authors.affiliation: National Cancer Institute, Vilnius, Lithuania. rasa.vanseviciute@nvi.lt.
authors.forename: Rasa
authors.initials: R
authors.lastname: Vansevičiūtė
authors.affiliation: National Cancer Institute, Vilnius, Lithuania. jonas.venius@nvi.lt.|Laboratory of Biomedical Physics, National Cancer Institute, Vilnius, Lithuania. jonas.venius@nvi.lt.
authors.forename: Jonas
authors.initials: J
authors.lastname: Venius
authors.affiliation: Faculty of Medicine, Vilnius University, Vilnius, Lithuania. olga.zukovskaja@gmail.com.
authors.forename: Olga
authors.initials: O
authors.lastname: Žukovskaja
authors.affiliation: National Cancer Institute, Vilnius, Lithuania. daiva.kanopiene@nvi.lt.
authors.forename: Daiva
authors.initials: D
authors.lastname: Kanopienė
authors.affiliation: National Cancer Institute, Vilnius, Lithuania. simona.letautiene@nvi.lt.|Faculty of Medicine, Vilnius University, Vilnius, Lithuania. simona.letautiene@nvi.lt.
authors.forename: Simona
authors.initials: S
authors.lastname: Letautienė
authors.affiliation: Laboratory of Biomedical Physics, National Cancer Institute, Vilnius, Lithuania. ricardas.rotomskis@nvi.lt.|Biophotonics Group, Laser Research Center, Vilnius University, Vilnius, Lithuania. ricardas.rotomskis@nvi.lt.
authors.forename: Ričardas
authors.initials: R
authors.lastname: Rotomskis
mesh_terms: D000328:Adult; D000622:Aminolevulinic Acid / Q000494:pharmacology; D003127:Colposcopy / Q000379:methods; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000494:pharmacology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods*; D014626:Vaginal Smears / Q000379:methods; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid