The authors declare that they have no competing interests.
RV performed all experiments of fluorescence measurements in vivo and together with JV, OŽ, DK, SL, RR drafted the manuscript. JV adjusted the equipment for the fluorescence measurements, performed the analysis of the fluorescence data, created the algorithm and diagnostic factor for differentiation between low and high risk changes in cervical tissue. OŽ analized recorded spectra and performed statistical processing. DK performed convetional colposcopy analysis (second opinion). SL designed and monitored the plan of investigation. RR contributed to the conception of the idea, discussed the data of experiments and critically reviewed the final manuscript. RV, JV, OŽ, DK, SL were involved in the design of the protocol and preparation, which was approved by the Vilnius regional ethics committee of biomedical research. All authors contributed to all stages of the experimental work and preparation of the manuscript, including the final one.
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.
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.
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.
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.
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- 5-Aminolevulinic-acid-based fluorescence spectroscopy and conventional colposcopy for in vivo detection of cervical pre-malignancy
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