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BMC Women's Health
Published in: BMC Women's Health 1/2015

Open Access 01-12-2015 | Research article

5-Aminolevulinic-acid-based fluorescence spectroscopy and conventional colposcopy for in vivo detection of cervical pre-malignancy

Authors: Rasa Vansevičiūtė, Jonas Venius, Olga Žukovskaja, Daiva Kanopienė, Simona Letautienė, Ričardas Rotomskis

Published in: BMC Women's Health | Issue 1/2015

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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.
Literature
1.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed
2.
Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, et al. European guidelines for quality assurance in cervical cancer screening. Second edition—summary document. Ann Oncol. 2010;21(3):448–58.CrossRefPubMedPubMedCentral
3.
4.
Arbyn M, Antoine J, Magi M, Smailyte G, Stengrevics A, Suteu O, et al. Trends in cervical cancer incidence and mortality in the Baltic countries. Bulgaria and Romania Int J Cancer. 2011;128:1899–907.CrossRefPubMed
5.
Wheeler CM, Hunt WC, Cuzick J, Langsfeld E, Robertson M, Castle PE. New Mexico HPV Pap registry steering committee the influence of type-specific human papillomavirus infections on the detection of cervical precancer and cancer: a population-based study of opportunistic cervical screening in the united states. Int J Cancer. 2014;135(3):624–34.CrossRefPubMedPubMedCentral
6.
Nair S, Pillai MR. Human papillomavirus and disease mechanisms: relevance to oral and cervical cancers. Oral Dis. 2005;11:350–9.CrossRefPubMed
7.
Singer A, Monaghan MJ, Quek SC. Lower Genital Tract Precancer. Colposcopy, pathology and treatment. 2nd ed. Oxford. Blacwell science; 2008.
8.
Tan JHJ, Wrede CDH. New technologies and advances in colposcopic assessment. Best Practice & Research Clinical Obstetrics and Gynaecology. 2011;25:667–77.CrossRefPubMed
9.
Bosgraaf RP, Mast PP, Struik-van der Zanden PH, Bulten J, Massuger LF, Bekkers RL. Overtreatment in a see-and-treat approach to cervical intraepithelial lesions. Obstet Gynecol. 2013;121(6):1209–16.CrossRefPubMed
10.
Aue-Aungkul A, Punyawatanasin S, Natprathan A, Srisomboon J, Kietpeerakool C. "See and treat" approach is appropriate in women with high-grade lesions on either cervical cytology or colposcopy. Asian Pac J Cancer Prev. 2011;12(7):1723–6.PubMed
11.
Palma PD, Rossi PG, Collina G, Buccoliero AM, Ghiringhello B, Lestani M, et al. The NTCC pathology group the risk of false-positive histology according to the reason for colposcopy referral in cervical cancer screening. Am J Clin Pathol. 2008;129:75–80.CrossRefPubMed
12.
Cremer ML, Peralta EI, Dheming SG, Jimenez ME, Davis-Dao CA, Alonzo TA, et al. Digital assessment of the reproductive tract versus colposcopy for directing biopsies in women with abnormal Pap smears. Journal of Lower Genital Tract Disease. 2010;14(1):5–10.CrossRefPubMed
13.
Guido RS, Jeronimo J, Schiffman M, Solomon D. ALTS Group The distribution of neoplasia arising on the cervix: results from the ALTS trial. Am J Obstet Gynecol. 2005;193(4):1331–7.CrossRefPubMed
14.
15.
16.
Costas B. Review of biomedical optical imaging—a powerful, non-invasive, non-ionizing technology for improving in vivo diagnosis. Meas Sci Technol. 2009;20(10):104020.CrossRef
17.
Johansson A, Kromer K, Sroka R, Stepp H. Clinical optical diagnostics: Status and perspectives. Medical Laser Application. 2008;23(4):155–74.CrossRef
18.
Rotomskis R, Streckytė G, Bagdonas S, Venius J. Optinės diagnostikos technologijos (optinė biopsija) (Optical diagnostics technologies (optical biopsy)). Vilnius: Vilnius University press; 2008.
19.
Brown JQ, Vishwanath K, Palmer GM, Ramanujam N. Advances in quantitative UV-visible spectroscopy for clinical and pre-clinical application in cancer. Curr Opin Biotechnol. 2009;20(1):119–31.CrossRefPubMedPubMedCentral
20.
Chang VT, Cartwright PS, Bean SM, Palmer GM, Bentley RC, Ramanujam N. Quantitative physiology of the precancerous cervix in vivo through optical spectroscopy. Neoplasia. 2009;11(4):325–32.CrossRefPubMedPubMedCentral
21.
Rotomskis R, Streckytė G. Fluorescencinė navikų diagnostika. (Fluorescence diagnostics of tumors.). Medicina. 2004;40(12):1219–30.PubMed
22.
Quan L. Role of optical spectroscopy using endogenous contrasts in clinical cancer diagnosis. World J Clin Oncol. 2011;2(1):50–63.CrossRef
23.
Badizadegan K, Backman V, Boone CW, Crum CP, Dasari RR, Georgakoudi I, et al. Spectroscopic diagnosis and imaging of invisible pre-cancer. Faraday Discuss. 2004;126:265–79.CrossRefPubMed
24.
Suhr MA, Hopper C, Jones L, George JG, Bown SG, MacRobert AJ. Optical biopsy systems for the diagnosis and monitoring of superficial cancer and precancer. Int J Oral Maxillofac Surg. 2000;29(6):453–7.CrossRefPubMed
25.
Jerjes WK, Upile T, Wong BJ, Betz CS, Sterenborg HJ, Witjes MJ, Veen van R, Biel MA, El-Naggar AK, Mosse CA, Olivo M, Richards-Kortum R. The future of medical diagnostics: review paper. Head Neck Oncol. 2011; 3:38.
26.
Sieroń A, Sieroń-Stołtny K, Kawczyk-Krupka A, Latos W, Kwiatek S, Straszak D, et al. The role of fluorescence diagnosis in clinical practice. Onco Targets Ther. 2013;6:977–82.PubMedPubMedCentral
27.
Moghissi K, Stringer MR, Dixon K. Fluorescence photodiagnosis in clinical practice. Photodiagnosis Photodyn Ther. 2008;5:235–7.CrossRefPubMed
28.
Ramanujam N, Mitchell MF, Mahadevan A, Thomsen S, Silva E, Richards-Kortum RR. In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm laser induced fluorescence. Proc Natl Acad Sci. 1994;91:10193–7.CrossRefPubMedPubMedCentral
29.
Ramanujam N, Mitchell MF, Mahadevan A, Thomsen S, Malpica A, Wright T, et al. Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN cpb using laser induced fluorescence spectra at multiple excitation wavelenghts). Lasers Surg Med. 1996;19:63–74.CrossRefPubMed
30.
Onizawa K, Okamura N, Saginoya H, Yoshida H. Characterization of autofluorescence in oral squamous cell carcinoma. Oral Oncol. 2003;39(2):150–6.CrossRefPubMed
31.
Zheng W, Soo KC, Sivanandan R, Olivo M. Detection of neoplasms in the oral cavity by digitized endoscopic imaging of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. Int J Oncol. 2002;21(4):763–8.PubMed
32.
Hillemanns P, Weingandt H, Baumgartner R, Diebold J, Xiang W, Stepp H. Photodetection of cervical intraepithelial neoplasia using 5-aminolevulinic acid-induced porphyrin fluorescence. Cancer. 2000;88(10):2275–82.CrossRefPubMed
33.
Collinet P, Jouve E, Regis C, Farine MO, Vinatier D, Cosson M, et al. Fluorescence diagnosis of cervical squamous intraepithelial lesions: A clinical feasibility study. Photodiagn Photodyn Ther. 2007;4(2):112–6.CrossRef
34.
Bogaards A, Aalders MC, Zeyl CC, de Blok S, Dannecker C, Hillemanns P, et al. Localization and staging of cervical intraepithelial neoplasia using double ratio fluorescence imaging. J Biomed Opt. 2002;7(2):215–20.CrossRefPubMed
35.
Vansevičiūtė R, Žukovskaja O, Venius J. Comparison of 5-aminolevulinic acid based fluorescence diagnostics with histology in the detection of cervical neoplasia. Medical Physics in the Baltic States: proceedings of the 11th international conference on medical physics. 2013; 11:12-4.
36.
Brookner C, Follen M, Boiko I, Galvan J, Thomsen S, Malpica A, et al. Tissue slices autofluorescence patterns in fresh cervical tissue. Photochem Photobiol. 2000;71:730–6.CrossRefPubMed
37.
Drezek R, Brookner C, Pavlova I, Boiko I, Malpica A, Lotan R, et al. Autofluorescence microscopy of fresh cervical tissue sections reveals alterations in tissue biochemistry with dysplasia. Photochem Photobiol. 2001;73:636–41.CrossRefPubMed
38.
Richards-Kortum R, Drezek R, Basen-Enquist K, Cantor SB, Utzinger U, Brookner C, Follen M. Cervical dysplasia diagnosis with fluorescence spectroscopy. Handbook of biomedical fluorescence. CRC Press; 2003. p. 265-313.
39.
Florkowski CM. Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios: communicating the performance of diagnostic tests. Clin Biochem Rev. 2008;29:83–7.
40.
Akobeng AK. Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Pediatrica. 2007;644:7.
41.
Sapozhnikova VV, Shakhova NM, Kamensky VA, Petrova SA, Snopova LB, Kuranov RV. Capabilities of fluorescence spectroscopy using 5-ALA and optical coherence tomography for diagnosis of neoplastic processes in the uterine cervix and vulva. Laser Phys. 2005;15(12):1664–73.
Metadata
Title
5-Aminolevulinic-acid-based fluorescence spectroscopy and conventional colposcopy for in vivo detection of cervical pre-malignancy
Authors
Rasa Vansevičiūtė
Jonas Venius
Olga Žukovskaja
Daiva Kanopienė
Simona Letautienė
Ričardas Rotomskis
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Women's Health / Issue 1/2015
Electronic ISSN: 1472-6874
DOI
https://doi.org/10.1186/s12905-015-0191-4

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