Description

Head and neck squamous cell carcinoma (HNSCC) develops from the epithelial lining of the oral cavity, pharynx, larynx and cervical oesophagus. HNSCC accounts for 5% of all new cases of cancer diagnosed in developed countries, and its incidence is rising. It is one of the most common cancers in the world, with around 900,000 new cases and 500,000 deaths per year [1,2].
Despite recent advances in diagnosis and treatment, the prognosis remains poor [3]. Local control of HNSCC remains a challenge, as local recurrence is the main oncological event. Even after surgical resection of the primary tumour with histologically clear margins, local recurrence may still occur in 10-30% of cases [4]. This may be explained by the difficulty in assessing minimal residual disease after tumor resection [4,5], and by the particular carcinogenesis of HNSCC, known as ‘field carcinogenesis’.
As HNSCC is mainly induced by tobacco and alcohol consumption, it develops in pre-cancerous mucosal changes characterized by tumor-associated genetic changes and morphological changes like dysplasia, usually not visible, and therefore often surrounding primary tumors. Some are easily visible, with leukoplakia being a common precancerous lesion that may precede invasive carcinomas [6]. Currently, the standard treatment algorithm is biopsy to exclude an invasive component and pathological grading of potential epithelial dysplasia (from mild to severe), one of the best predictive markers of malignant transformation of leukoplakia [7].
However, most precancerous fields are not macroscopically visible and are only detected in the resection specimens by microscopic examination of the surgical margins. Due to the size of these precancerous fields and the fact that most of them are not visible, they may remain undetected after tumor resection and may lead to potential local relapses and/or second primary tumors.
Early detection of malignant lesions and improved local control are therefore crucial to achieving acceptable oncological outcomes, as local recurrence remains the main cause of treatment failure [8]. However, white light examination, palpation and standard radiological examination often fail to distinguish malignant lesions from premalignant lesions, or the tumor from surrounding tissue. Biopsy and histopathological examination of suspected lesions are therefore the gold standard, but they are invasive, time-consuming and can lead to underestimation or misdiagnosis due to sampling bias. There is a strong need for non-invasive alternatives to avoid repeated biopsies, which are associated with cost and morbidity, in order to monitor potentially premalignant lesions over a period of several years. Recently, new optical tools (confocal microscopy, narrow-band imaging, diagnostic adjuncts) have been evaluated for the detection of premalignant and malignant lesions of the oral cavity, but no clear benefit has yet been demonstrated [9].
In recent years, Mueller polarimetric imaging has attracted considerable interest for a wide range of biomedical applications [10-11]. In particular, this technique has shown great promise for the early diagnosis of cancer [12-16].
The aim of this thesis is to test Mueller polarimetric imaging as a new tool for improving the detection and treatment of CETEC.

Skills required

Optics and optical instrumentation. Optical measurements and signal processing. Solid knowledge of physics and linear algebra. Willingness to work in a multidisciplinary environment. Strong motivation for ongoing interaction with the medical world. Good knowledge of English. Good knowledge of Matlab and other programming languages.

Bibliography

[1] Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424.

[2] Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin. 2019, 69, 7–34.

[3] Longo DL, Chow LQM. Head and Neck Cancer. N Engl J Med 2020;382(1):60–72.

[4] Pierik, A.S.; Leemans, C.R.; Brakenhoff, R.H. Resection Margins in Head and Neck Cancer Surgery: An Update of Residual Disease and Field Cancerization. Cancers 2021, 13, 2635.

[5] Evans, M.; Beasley, M. Target delineation for postoperative treatment of head and neck cancer. Oral Oncol. 2018, 86, 288–295.

[6] Evren, I.; Brouns, E.R.; Wils, L.J.; Poell, J.B.; Peeters, C.F.W.; Brakenhoff, R.H.; Bloemena, E.; de Visscher, J. Annual malignant transformation rate of oral leukoplakia remains consistent: A long-term follow-up study. Oral Oncol. 2020, 110, 105014.

[7] Wils, L.J.; Poell, J.B.; Evren, I.; Koopman, M.S.; Brouns, E.; de Visscher, J.; Brakenhoff, R.H.; Bloemena, E. Incorporation of differentiated dysplasia improves prediction of oral leukoplakia at increased risk of malignant progression. Modern Pathol. 2020,33, 1033–1040.

[8] Temam S, Casiraghi O, Lahaye J-B, Bosq J, Zhou X, Julieron M, et al. Tetranucleotide microsatellite instability in surgical margins for prediction of local recurrence of head and neck squamous cell carcinoma. Clin Cancer Res 2004;10 (12):4022–8.

[9] Villard A, Breuskin I, Casiraghi O, Asmandar S, Laplace-Builhe C, Abbaci M, Moya Plana A. Confocal laser endomicroscopy and confocal microscopy for head and neck cancer imaging: Recent updates and future perspectives. Oral Oncol. 2022 Apr;127:105826.

[10] J. Rehbinder, J. Vizet, J. Park, R. Ossikovski, J.-C. Vanel, A. Nazac, and A. Pierangelo “Depolarization imaging for fast and non-invasive monitoring of cervical microstructure remodeling in vivo during pregnancy” Scientific Reports, 12, 12321 (2022). doi: 10.1038/s41598-022-15852-w.

[11] H. Yang, B. Liu, J. Park, O. Blaise, C. Duchesne, B. Honnorat, J. Vizet, A. Rousseau, and A. Pierangelo, “Mueller Polarimetric Imaging as a tool for detecting the effect of Non-Thermal Plasma treatment on the skin”, Biomed. Opt. Express, 14(6), 2736-2755 (2023). doi: 10.1364/BOE.482753.

[12] J. Rehbinder, H. Haddad, S. Deby, B. Teig, A. Nazac, T. Novikova, A. Pierangelo, F. Moreau “Ex vivo Mueller polarimetric imaging of the uterine cervix: a first statistical evaluation” 21(7), 071113 (2016), J. Biomed. Optics (Special Issue of Journal of Biomedical Optics on Polarized Light). doi: 10.1117/1.JBO.21.7.071113

[13] J. Vizet, J. Rehbinder, S. Deby, S. Roussel, A. Nazac, R. Soufan, C. Genestie, C. Haie-Meder, H. Fernandez, F. Moreau and A. Pierangelo “In vivo imaging of uterine cervix with a Mueller polarimetric colposcope”, Scientific Reports, 7(1), 2471 (2017). doi: 10.1038/s41598-017-02645-9.

[14] C. Heinrich, J. Rehbinder, A. Nazac, B. Teig, A. Pierangelo, and J. Zallat 'Mueller polarimetric imaging of biological tissues: classification in a decision-theoretic framework.' JOSA A, 35 (12), 2046-2057, (2018). doi: 10.1364/JOSAA.35.002046.

[15] J. Vizet, J. Rehbinder, S. Deby, S. Roussel, A. Nazac, R. Soufan, C. Genestie, C. Haie-Meder, H. Fernandez, F. Moreau and A. Pierangelo 'First Demonstration of in vivo Mueller Polarimetric Imaging on Human Uterine Cervix.' CLEO: Applications and Technology. Proceedings in Optical Society of America, p. AM2J. 5, (2018). doi : 10.1364/CLEO_AT.2018.AM2J.5

[16] J. Park, A. Lindberg, J. Vizet, J. Rehbinder, C. Gennet, J. C Vanel, A. Nazac, E. Debras, P. Capmas, H. Fernandez, and A. Pierangelo 'Cervical cancer diagnostics with a multispectral Mueller polarimetric colposcope.' Proceedings in European Conference on Biomedical Optics. Optical Society of America, p. 11073_9, (2019). doi: 10.1117/12.2526934.

Keywords

Medical imaging, Mueller polarimetric imaging, Head and neck squamous cell carcinoma, Screening / Early Diagnosis, Histopathological mapping/Delineation of tumor extension, Postoperative follow-up