Photodetection of cervical intraepithelial neoplasia using 5-aminolevulinic acid-induced porphyrin fluorescence.
BACKGROUND
Screening for cervical carcinoma and its precursors is based on cervical cytology and diagnostic colposcopy. Despite the decrease in the incidence of cervical carcinoma in countries with a good screening program, this rate of decline is leveling off. Known problems are false-negative rates of cytology and low specificity of colposcopy. This clinical study examined the diagnostic potential of porphyrin fluorescence in patients with cervical intraepithelial neoplasia Grade 1-3 (CIN 1-3).


METHODS
Sixty-eight women attending our colposcopy clinic underwent a gynecologic examination, including cytology, human papillomavirus (HPV) testing, and colposcopy. They received 10 mL 0.5% or 1.0% 5-aminolevulinic acid (5-ALA) topically. After 30-360 minutes, real-time image analysis was performed, and spectra were obtained from 685 sites.


RESULTS
Due to rapid photobleaching, 0.5% 5-ALA proved ineffective for fluorescence assessment. Using 1% 5-ALA, the authors found that fluorescence intensities correlated with incubation time; however, fluorescence contrast showed a maximum at 60-90 minutes (ratio 11:1). HPV DNA positive lesions showed significantly higher fluorescence. Fluorescence imaging after 60-90 minutes achieved similar sensitivity and specificity compared with colposcopy in detecting CIN with 94% and 51% versus 95% and 50%, respectively. However, the specificity was markedly improved by fluorescence spectroscopy, achieving 75%. The evaluation of spectral measurements revealed significantly higher values for CIN compared with normal tissue and for CIN 2/3 compared with CIN 1 (P < 0.001).


CONCLUSIONS
Using a time interval of 60-90 minutes after topical application of 1% 5-ALA, the authors observed specific porphyrin fluorescence of CIN. Fluorescence spectroscopy promises to become a valuable tool for the diagnosis of CIN.
Hillemanns
P
P
Department of Obstetrics and Gynecology, Klinikum Grosshadern, Ludwig-Maximilian-University, Munich, Germany.
Weingandt
H
H
Baumgartner
R
R
Diebold
J
J
Xiang
W
W
Stepp
H
H
D000328:Adult; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid