10.14639/0392-100X-N0801
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Wei Liu
ACTA Otorhinolaryngologica Italica
Confocal laser endomicroscopy; head and neck squamous cell carcinoma; oral potentially malignant disorders; dysplasia; fluorescent molecular imaging
Current evidence on confocal laser endomicroscopy for noninvasive head and neck cancer imaging
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Letters to the Editor-in-Chief
2020-12-03
2020-04-18
2020-12-04
2020-12-04
1
Wei Liu
2020/12/03
10.14639/0392-100X-N0801
Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, College of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
1827-675X
5
Confocal laser endomicroscopy; head and neck squamous cell carcinoma; oral potentially malignant disorders; dysplasia; fluorescent molecular imaging
Current evidence on confocal laser endomicroscopy for noninvasive head and neck cancer imaging
https://www.actaitalica.it/article/download/801/469
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2020;40:396-398; doi: 10.14639/0392-100X-N0801




Letter to the Editor


Current evidence on confocal laser endomicroscopy
for noninvasive head and neck cancer imaging
Evidenze scientifiche attuali sulla endomicroscopia confocale laser nell’imaging
del tumore non invasivo del distretto testa e collo
Xi Yang1,2, Wei Liu2
1
 Department of Oral and Maxillofacial-Head and Neck Oncology, Fengcheng Hospital of Fengxian District, Shanghai, China;
2
 Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, College of Stomatology,
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of
Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China


KEY WORDS: confocal laser endomicroscopy, head and neck squamous cell carcinoma,
oral potentially malignant disorders, dysplasia, fluorescent molecular imaging
PAROLE CHIAVE: endomicroscopia laser confocale, carcinoma spinocellulare testa e
collo, lesioni orali potenzialmente maligne, displasia, imaging molecolare a fluorescenza



Dear Editor,                                                                                Received: April 18, 2020
                                                                                            Accepted: April 28, 2020
We read with interest the article entitled “Probe-based confocal laser en-
domicroscopy in detecting malignant lesions of vocal folds” recently pub-                   Correspondence
lished in Acta Otorhinolaryngologica Italica by Goncalves et al. 1. The                     Wei Liu
authors determined the diagnostic value and inter-rater reliability of confo-               Department of Oral and Maxillofacial-Head and
                                                                                            Neck Oncology, Shanghai Ninth People’s Hospital,
cal laser endomicroscopy (CLE) by comparing 58 video sequences of 3 pa-                     Shanghai 200011, China
tients with squamous cell carcinomas (SCC) and 4 patients with benign al-                   E-mail: liuweb@hotmail.com
terations of the vocal folds 1. CLE imaging features of SCC compared with
the benign alterations were well characterised 1, but the current evidence                  Funding
                                                                                            This work was supported by Fengxian District
on CLE imaging in noninvasive detection of HNSCC is making progress                         Clinical Diagnosis & Treatment Center of Oral
and needs to be significantly expanded upon (Tab. I). This Letter aims to                   and Maxillofacial-Head and Neck Oncology
provide the reader with an up-to-date review of the literature on CLE in the                (fxlczlzx-a-201705) and Shanghai Municipal
                                                                                            Health Committee (202040327).
setting of HNSCC. We classify the research topics of current investigations
into CLE head and neck imaging, and briefly discuss current practices and                   Conflict of interest
challenges that implicate future directions.                                                The Authors declare no conflict of interest.
In studies before 2014, the main objective of preliminary studies was to
investigate the CLE imaging characteristics of head and neck cancer tis-                      How to cite this article: Yang X, Liu W. Current
sue compared to normal mucosa and surgical margins (reviewed in Abbaci                        evidence on confocal laser endomicroscopy for
                                                                                              noninvasive head and neck cancer imaging. Acta
et al. 2). Earlier studies have shown that by using CLE, micro-anatomical                     Otorhinolaryngol Ital 2020;40:396-398. https://
structures of normal mucosa/margins and cancerous lesions can be well                         doi.org/10.14639/0392-100X-N0801
identified, allowing for differentiation of malignant and benign mucosal.
                                                                                            © Società Italiana di Otorinolaringoiatria
However, these results should be interpreted prudently for several rea-                     e Chirurgia Cervico-Facciale
sons: very small sample size, different measurement devices used, lack
of diagnostic criteria based on micro-imaging of CLE. In addition, field                                   OPEN ACCESS
of view and depth penetration of this technology have not yet been well                     This is an open access article distributed in accordance with
                                                                                            the CC-BY-NC-ND (Creative Commons Attribution-Non-
addressed 2.                                                                                Commercial-NoDerivatives 4.0 International) license. The
Starting in 2014, the main objective of prior studies was to evaluate wheth-                article can be used by giving appropriate credit and mentio-
                                                                                            ning the license, but only for non-commercial purposes and
er CLE is useful in diagnosing HNSCC 3-8. According to preliminary da-                      only in the original version. For further information: https://
ta 1,3,6-8, the sensitivity and specificity of diagnosing SCC was reported to               creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                                                                              CLE for head and neck cancer




be 85.0-95.3% and 72.0-100%, respectively. Addition-                                         head and neck cancer imaging with EpCAM and EGFR
ally, the interobserver accuracy and reliability of CLE                                      antibodies conjugated to fluorescent labels 9,10. When com-
for discrimination of head and neck lesions from normal                                      bined with the molecular imaging capabilities of CLE at the
mucosa has also been investigated 4-6. Intriguingly, the                                     cellular level, these new fluorescent targets can contribute
feasibility of automated analysis and classification of                                      to the currently pursued topic of personalised medicine in
cancerous tissue in CLE head and neck imaging using                                          the field of head and neck cancer, by making it possible to
deep learning has been demonstrated 7,8. Although the                                        predict the cells’ response to the molecular imaging guided
results are promising, they are limited to mainly small                                      diagnosis and therapy.
descriptive studies. The standardised diagnostic proto-                                      In summary, the noninvasive point-of-care CLE for head
cols as well as clinically relevant classification systems                                   and neck imaging at the cellular level, as a new emerg-
for head and neck diseases have not yet been described.                                      ing science, is of great promise for research, especially in
Moreover, the integration between pathologist and clini-                                     molecular targeted chairside diagnosis and intraoperative
cian/surgeon in the review process of CLE imaging has                                        normal margins. Multi-institutional studies on the three
not been elucidated.                                                                         aforementioned research classifications are warranted to
One of the greatest advantages of CLE with fluorescence is                                   overcome the drawbacks and consolidate the value of CLE.
its potential for multiplex analyses in which morphological                                  The dynamic observation of early malignant changes at the
information can be combined with molecular and/or func-                                      cellular level is a crucial element in the understanding of
tional markers. Alterations in molecular and/or functional                                   patient-specific information and today, noninvasive CLE is
properties of a cancerous tissue can be translated into sig-                                 probably the most versatile technology to face this chal-
nificant and optically measurable changes in fluorescent                                     lenge. Nevertheless, substantial researches are still needed
signals. In vivo molecular imaging of gastrointestinal can-                                  in order to promote fluorescence molecular imaging tech-
cer using CLE by targeting EGFR and VEGF has been                                            niques to the status of routine use in clinical practice for
demonstrated; this concept was recently applied to CLE                                       HNSCC.



Table I. Summary of the English-language literature of confocal laser endomicroscopy for diagnostic assessment of head and neck squamous cell carcinoma
(SCC).
 Year of       First         Country       Manufacturer       No. of subjects Subject setting            Aim of study       Sensitivity   Specificity
 publication  author                                            and location                                                     %             %
 2019             Goncalves        Germany         CellVizio, France         Vocal folds         4 benign vs. 3       Diagnostic assessment    91.4-96.6        100
                   et al. 1                                                                          SCC                 and interobserver
                                                                                                                             agreement
 2014             Nathan et           USA          CellVizio, France            Oral            12 leukoplakia               Diagnostic          85.7           100
                    al. 3                                                                          vs. 9 SCC               assessment a
 2016             Moore et            USA          CellVizio, France            Oral            6 non-dysplasia            Interobserver          NA             NA
                    al. 4                                                                       vs. 7 dysplasia              agreement
                                                                                                  vs. 11 SCC
 2016             Linxweiler       Germany         CellVizio, France             HN              50 normal vs.          Interobserver             NA             NA
                    et al. 5                                                                       135 SCC               agreement b
 2016              Oetter et       Germany         CellVizio, France            Oral               45 normal       Diagnostic assessment         95.3           88.9
                     al. 6                                                                          50 SCC            and interobserver
                                                                                                                          agreement
 2016             Dittberner       Germany         CellVizio, France     Oral, oropharynx,      Self control of 12 Automated Diagnostic          85.0           72.0
                    et al. 7                                                   others            normal margins          assessment
                                                                                                     and SCC
 2017             Aubreville       Germany         CellVizio, France             oral           Self control of 12 Automated Diagnostic          86.6           90.0
                   et al. 8                                                                      normal margins          assessment
                                                                                                     and SCC
 2017            Englhard et       Germany         CellVizio, France             HN              5 normal vs. 11 EGFR/EpCAM-targeted              NA             NA
                     al. 9                                                                             SCC              micro-imaging
 2019            Watermann         Germany             Optiscan,                 NA              Gingiva normal     EGFR nanoparticles-           NA             NA
                   et al. 10                           Australia                                 vs. Oropharynx        targeted micro-
                                                                                                       SCC                 imaging
HN: head and neck sites being not-specified; NA: not available. a SCC vs. non-dysplasia. b using formalin-fixed tissue specimens.




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