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.