Criteria for a severe disease were: annual rate of surgical endoscopy ≥ 5, spread to the lung, carcinomatous transformation or death. We conducted a multi-stage study with image analysis.

First, with Hematoxylin and eosin (HE) digital slides of papilloma, we searched for morphological patterns associated with a severe JoRRP using a deep-learning algorithm. Then, immunohistochemistry with antibody against p53 and p63 was performed on sections of FFPE samples of laryngeal papilloma obtained between 2008 and 2018. Immunostainings were quantified according to the staining intensity through two automated workflows: one using machine learning, the other using deep learning. Twenty-four patients had severe disease.

For the HE analysis, no significative results were obtained with cross-validation. For immunostaining with anti-p63 antibody, we found similar results between the two image analysis methods. Using machine learning, we found 23.98% of stained nuclei for medium intensity for mild JoRRP vs. 36.1% for severe JoRRP (p = 0.041); and for medium and strong intensity together, 24.14% for mild JoRRP vs. 36.9% for severe JoRRP (p = 0.048). Using deep learning, we found 58.32% for mild JoRRP vs. 67.45% for severe JoRRP (p = 0.045) for medium and strong intensity together. Regarding p53, we did not find any significant difference in the number of nuclei stained between the two groups of patients. In conclusion, we highlighted that immunochemistry with the anti-p63 antibody is a potential biomarker to predict the severity of the JoRRP.

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Authors: 

Charles Lépine1,2, Paul Klein 3, Thibault Voron1, Marion Mandavit 1, Dominique Berrebi 4, Sophie Outh-Gauer 1,2, Hélène Péré1,5, Louis Tournier 4, Franck Pagès 6, Eric Tartour 1,6, Thomas Le Meur 3, Sylvain Berlemont 3, Natacha Teissier 7, Mathilde Carlevan8, Nicolas Leboulanger 8, Louise Galmiche 9 and Cécile Badoual 1,2 

1 INSERM-U970, PARCC, Université de Paris, Paris, France,

2 Department of Pathology, Hôpital Européen Georges-Pompidou, APHP, Paris, France

3 KeenEye, Paris, France

4 Department of Pathology, Hôpital Robert Debré, APHP, Paris, France

5 Department of Virology, Hôpital Européen Georges-Pompidou, APHP, Paris, France

6 Department of Immunology, Hôpital Européen Georges-Pompidou, APHP, Paris, France

7 Department of Pediatric ENT Surgery, Hôpital Robert Debré, APHP, Paris, France

8 Department of Pediatric ENT Surgery, Hôpital Necker-Enfants Malades, APHP, Paris, France

9 Department of Pathology, Hôpital Necker-Enfants Malades, APHP, Paris, France