J. Meyers, E. Ryndock, M. J. Conway, C. Meyers, and R. Robison, « Susceptibility of high-risk human papillomavirus type 16 to clinical disinfectants, J. Antimicrob. Chemother, vol.69, issue.6, pp.1546-1550, 2014.

J. Guan, Cryoelectron Microscopy Maps of Human Papillomavirus 16 Reveal L2 Densities and Heparin Binding Site », Structure, vol.25, pp.253-263, 2017.

K. Van-doorslaer, ICTV Virus Taxonomy Profile: Papillomaviridae », 2018.

E. De-villiers, C. Fauquet, T. R. Broker, H. Bernard, and H. Zur-hausen, Classification of papillomaviruses », Virology, vol.324, pp.17-27, 2004.

M. Segondy, « Classification des papillomavirus (HPV) », Revue Francophone des Laboratoires, pp.23-25, 2008.

M. M. Jelen, « Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences, J. Virol, vol.90, issue.11, pp.5503-5513, 2016.

M. M. Jelen, « Global genomic diversity of human papillomavirus 6 based on 724 isolates and 190 complete genome sequences, J. Virol, vol.88, pp.7307-7316, 2014.

S. De-sanjosé, « Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis, Lancet Infect Dis, vol.7, issue.7, pp.453-459, 2007.

H. Iarc and . Papillomaviruses,

S. R. Skinner, « Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study, Int. J. Cancer, vol.138, issue.10, pp.2428-2438, 2016.

D. Forman, Global burden of human papillomavirus and related diseases, vol.30, pp.12-23, 2012.

Z. C. Wood, C. J. Bain, D. D. Smith, D. C. Whiteman, and E. A. Antonsson, « Oral human papillomavirus infection incidence and clearance: a systematic review of the literature, J. Gen. Virol, vol.98, issue.4, pp.519-526, 2017.

F. Dayyani, C. J. Etzel, M. Liu, C. Ho, S. M. Lippman et al., « Metaanalysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC), Head Neck Oncol, vol.2, p.15, 2010.

A. R. Kreimer, G. M. Clifford, P. Boyle, and E. S. Franceschi, « Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review, Cancer Epidemiol. Biomarkers Prev, vol.14, issue.2, pp.467-475, 2005.

N. Muñoz, Human papillomavirus and cancer: the epidemiological evidence, J. Clin. Virol, vol.19, issue.2, pp.1-5, 2000.

S. V. Porceddu, A TNM classification for HPV+ oropharyngeal cancer, The Lancet Oncology, vol.17, issue.4, pp.403-404, 2016.

A. N. Burchell, R. L. Winer, S. De-sanjosé, E. L. Franco, and . Chapter, Epidemiology and transmission dynamics of genital HPV infection, vol.24, 2006.

K. M. Johnson, R. C. Kines, J. N. Roberts, D. R. Lowy, J. T. Schiller et al., Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus, J. Virol, vol.83, issue.5, pp.2067-2074, 2009.

T. D. Culp, L. R. Budgeon, M. P. Marinkovich, G. Meneguzzi, and N. D. Christensen, « Keratinocyte-secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells, J. Virol, vol.80, pp.8940-8950, 2006.

D. Pyeon, S. M. Pearce, S. M. Lank, P. Ahlquist, and P. F. Lambert, « Establishment of human papillomavirus infection requires cell cycle progression, PLoS Pathog, vol.5, issue.2, 2009.

M. Bergant-maru?i?, M. A. Ozbun, S. K. Campos, M. P. Myers, and E. L. Banks, « Human papillomavirus L2 facilitates viral escape from late endosomes via sorting nexin 17, Traffic, vol.13, issue.3, pp.455-467, 2012.

A. A. Mcbride, « Replication and partitioning of papillomavirus genomes, Adv. Virus Res, vol.72, pp.155-205, 2008.

C. B. Buck, C. D. Thompson, Y. S. Pang, D. R. Lowy, and J. T. Schiller, « Maturation of papillomavirus capsids, J. Virol, vol.79, issue.5, pp.2839-2846, 2005.

P. B. Mcintosh, « Structural analysis reveals an amyloid form of the human papillomavirus type 16 E1--E4 protein and provides a molecular basis for its accumulation, J. Virol, vol.82, pp.8196-8203, 2008.

J. S. Horton and A. J. Stokes, « The transmembrane channel-like protein family and human papillomaviruses, Oncoimmunology, vol.3, 2014.

A. G. Ostör, « Natural history of cervical intraepithelial neoplasia: a critical review, Int. J. Gynecol. Pathol, vol.12, issue.2, pp.186-192, 1993.

M. Scheffner, B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley, « The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53, Cell, vol.63, issue.6, pp.1129-1136, 1990.

T. Veldman, I. Horikawa, J. C. Barrett, and R. Schlegel, « Transcriptional activation of the telomerase hTERT gene by human papillomavirus type 16 E6 oncoprotein, J. Virol, vol.75, issue.9, pp.4467-4472, 2001.

L. Sherman and R. Schlegel, Serum-and calcium-induced differentiation of human keratinocytes is inhibited by the E6 oncoprotein of human papillomavirus type 16. », J. Virol, vol.70, issue.5, pp.3269-3279, 1996.

K. Zerfass, A. Schulze, D. Spitkovsky, V. Friedman, B. Henglein et al., « Sequential activation of cyclin E and cyclin A gene expression by human papillomavirus type 16 E7 through sequences necessary for transformation, J. Virol, vol.69, issue.10, pp.6389-6399, 1995.

B. Ruttkay-nedecky, « Relevance of infection with human papillomavirus: The role of the p53 tumor suppressor protein and E6/E7 zinc finger proteins (Review), International Journal of Oncology, vol.43, issue.6, pp.1754-1762, 2013.

C. , « [HPV (Human Papilloma Virus) implication in other cancers than gynaecological] », Rev Med Interne, vol.36, issue.8, pp.540-547, 2015.

C. Picard and A. Belot, « [Type I interferonopathies. Literature review] », Rev Med Interne, 2016.

U. A. Hasan, « TLR9 expression and function is abolished by the cervical cancerassociated human papillomavirus type 16, J. Immunol, vol.178, issue.5, pp.3186-3197, 2007.

L. V. Ronco, A. Y. Karpova, M. Vidal, and P. M. Howley, « Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity, Genes Dev, vol.12, issue.13, pp.2061-2072, 1998.

M. S. Campo, « HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells, Virology, vol.407, issue.1, pp.137-142, 2010.

M. Stanley, Immune responses to human papillomavirus, vol.24, pp.16-22, 2006.

K. Middleton, « Organization of Human Papillomavirus Productive Cycle during Neoplastic Progression Provides a Basis for Selection of Diagnostic Markers, J Virol, vol.77, pp.10186-10201, 2003.

M. Pett and N. Coleman, « Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis?, J. Pathol, vol.212, issue.4, pp.356-367, 2007.

M. Rusan, Y. Y. Li, and P. S. Hammerman, Genomic Landscape of Human Papillomavirus-Associated Cancers, vol.21, pp.2009-2019, 2015.

D. Lee, « Human papillomavirus E2 down-regulates the human telomerase reverse transcriptase promoter, J. Biol. Chem, vol.277, pp.27748-27756, 2002.

A. J. Klingelhutz and A. Roman, « Cellular transformation by human papillomaviruses: lessons learned by comparing high-and low-risk viruses, Virology, vol.424, issue.2, pp.77-98, 2012.

A. C. Jung, « Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma », Int. J. Cancer, vol.126, issue.8, pp.1882-1894

D. Holzinger, « Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma », Int. J. Cancer, vol.140, p.2017

J. J. Carter, « The natural history of human papillomavirus type 16 capsid antibodies among a cohort of university women, J. Infect. Dis, vol.174, issue.5, pp.927-936, 1996.

C. Liang, « Biomarkers of HPV in head and neck squamous cell carcinoma, Cancer Res, vol.72, pp.5004-5013, 2012.

H. Mirghani, « Diagnosis of HPV-driven head and neck cancer with a single test in routine clinical practice, Mod. Pathol, vol.28, pp.1518-1527, 2015.

J. A. Bishop, « Detection of transcriptionally active high-risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mRNA in situ hybridization method, Am. J. Surg. Pathol, vol.36, pp.1874-1882

J. Augustin, « HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population, Mod. Pathol., juin, 2018.

E. Prigge, M. Arbyn, M. Von-knebel-doeberitz, and E. M. Reuschenbach, « Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis », Int. J. Cancer, vol.140, issue.5, pp.1186-1198, 2017.

J. S. Lewis, « p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status, Am. J. Surg. Pathol, vol.34, issue.8, pp.1088-1096, 2010.

A. K. El-naggar, J. K. Chan, J. R. Grandis, T. Takata, P. J. Slootweg et al., WHO classification of head and neck tumours, International Agency for Research on Cancer, 2017.

N. Muñoz, X. Castellsagué, A. B. De-gonzález, L. Gissmann, and . Chapter, HPV in the etiology of human cancer, vol.24, 2006.

D. Novakovic, « A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program, J. Infect. Dis, vol.217, issue.2, pp.208-212, 2018.

, Recommandations vaccinales contre les infections à papillomavirus humains chez les hommes, 2016.

, Infections à HPV des jeunes filles : révision de l'âge de vaccination, 2012.

L. Fonteneau, J. P. Guthmann, L. Bruhl, and D. , Estimation des couvertures vaccinales en France à partir de l'Échantillon généraliste des bénéficiaires (EGB) : exemples de la rougeole, de l'hépatite B et de la vaccination HPV. Numéro thématique. De nouveaux outils pour améliorer la mesure de la couverture vaccinale en France, 2013.

, « Vaccination contre les infections à HPV et risque de maladies auto-immunes : une étude Cnamts/ANSM rassurante -Point d'information -ANSM : Agence nationale de sécurité du médicament et des produits de santé

N. Andrews, J. Stowe, and E. E. Miller, « No increased risk of Guillain-Barré syndrome after human papilloma virus vaccine: A self-controlled case-series study in England, Vaccine, vol.35, issue.13, p.2017

H. Kashima, P. Mounts, B. Leventhal, and R. H. Hruban, Sites of predilection in recurrent respiratory papillomatosis, vol.102, pp.580-583, 1993.

E. Ullman, On the aetiology of the laryngeal papilloma, Acta Otolaryngol, issue.5, pp.317-334, 1923.

A. J. Donne, L. Hampson, J. J. Homer, and I. N. Hampson, The role of HPV type in Recurrent Respiratory Papillomatosis, vol.74, pp.7-14

B. J. Wiatrak, D. W. Wiatrak, T. R. Broker, and L. Lewis, « Recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population, Laryngoscope, vol.114, issue.2, pp.1-23, 2004.

M. Gabbott, Y. E. Cossart, A. Kan, M. Konopka, R. Chan et al., « Human papillomavirus and host variables as predictors of clinical course in patients with juvenile-onset recurrent respiratory papillomatosis, J. Clin. Microbiol, vol.35, pp.3098-3103, 1997.

P. Draganov, S. Todorov, I. Todorov, T. Karchev, and Z. Kalvatchev, « Identification of HPV DNA in patients with juvenile-onset recurrent respiratory papillomatosis using SYBR Green real-time PCR », Int. J. Pediatr. Otorhinolaryngol, vol.70, issue.3, pp.469-473, 2006.

P. Dickens, G. Srivastava, S. L. Loke, and E. S. Larkin, « Human papillomavirus 6, 11, and 16 in laryngeal papillomas, J. Pathol, vol.165, issue.3, pp.243-246, 1991.

M. Peñaloza-plascencia, H. Montoya-fuentes, S. E. Flores-martínez, F. J. Fierro-velasco, J. M. Peñaloza-gonzález et al., Molecular identification of 7 human papillomavirus types in recurrent respiratory papillomatosis, vol.126, pp.1119-1123, 2000.

M. Jamshidi, « The impact of human papillomavirus (HPV) types 6, 11 in women with genital warts, Arch. Gynecol. Obstet, vol.286, issue.5, pp.1261-1267, 2012.

M. J. Silverberg, P. Thorsen, H. Lindeberg, L. A. Grant, and K. V. Shah, Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis, vol.101, pp.645-652, 2003.

M. J. Silverberg, P. Thorsen, H. Lindeberg, L. Ahdieh-grant, and K. V. Shah, « Clinical Course of Recurrent Respiratory Papillomatosis in Danish Children, Arch Otolaryngol Head Neck Surg, vol.130, issue.6, pp.711-716, 2004.

V. Gerein, S. Schmandt, N. Babkina, N. Barysik, W. Coerdt et al., « Human papilloma virus (HPV)-associated gynecological alteration in mothers of children with recurrent respiratory papillomatosis during long-term observation, Cancer Detect. Prev, vol.31, issue.4, pp.276-281, 2007.

E. M. Smith, M. A. Parker, L. M. Rubenstein, T. H. Haugen, E. Hamsikova et al., « Evidence for vertical transmission of HPV from mothers to infants, Infect Dis Obstet Gynecol, vol.2010, p.326369, 2010.

X. Castellsagué, « Human Papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain, BMC Infect Dis, vol.9, p.74, 2009.

P. Liu, L. Xu, Y. Sun, and Z. Wang, « The prevalence and risk of human papillomavirus infection in pregnant women, Epidemiol. Infect, vol.142, issue.8, pp.1567-1578, 2014.

V. R. Bonagura, « Enriched HLA-DQ3 phenotype and decreased class I major histocompatibility complex antigen expression in recurrent respiratory papillomatosis, Clin. Diagn. Lab. Immunol, vol.1, issue.3, pp.357-360, 1994.

V. R. Bonagura, « Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect against developing the severe form of recurrent respiratory papillomatosis, Hum. Immunol, vol.71, issue.2, pp.212-219

C. M. Gelder, « HLA Class II Polymorphisms and Susceptibility to Recurrent Respiratory Papillomatosis, J. Virol, vol.77, issue.3, pp.1927-1939, 2003.

V. R. Bonagura, « HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis, Hum Immunol, vol.65, issue.8, pp.773-782, 2004.

V. R. Bonagura, L. Hatam, J. Devoti, F. Zeng, and B. M. Steinberg, « Recurrent respiratory papillomatosis: altered CD8(+) T-cell subsets and T(H)1/T(H)2 cytokine imbalance, Clin. Immunol, vol.93, issue.3, pp.302-311, 1999.

V. R. Bonagura, « Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus-6 and -11, APMIS, vol.118, pp.455-470, 2010.

A. Vambutas, V. R. Bonagura, and B. M. Steinberg, « Altered Expression of TAP-1 and Major Histocompatibility Complex Class I in Laryngeal Papillomatosis: Correlation of TAP-1 with Disease, Clin Diagn Lab Immunol, vol.7, issue.1, pp.79-85, 2000.

P. Campisi, M. Hawkes, K. Simpson, and . Et-canadian, Juvenile Onset Recurrent Respiratory Papillomatosis Working Group, « The epidemiology of juvenile onset recurrent respiratory papillomatosis derived from a population level national database, Laryngoscope, vol.120, issue.6, pp.1233-1245, 2010.

L. R. Armstrong, « Incidence and prevalence of recurrent respiratory papillomatosis among children in Atlanta and Seattle, Clin. Infect. Dis, vol.31, issue.1, pp.107-109, 2000.

H. Lindeberg and O. Elbrønd, « Laryngeal papillomas: the epidemiology in a Danish subpopulation 1965-1984 », Clin Otolaryngol Allied Sci, vol.15, issue.2, pp.125-131, 1990.

M. Marsico, V. Mehta, B. Chastek, K. Liaw, and C. Derkay, « Estimating the incidence and prevalence of juvenile-onset recurrent respiratory papillomatosis in publicly and privately insured claims databases in the United States, Sex Transm Dis, vol.41, issue.5, pp.300-305, 2014.

C. S. Derkay, D. J. Malis, G. Zalzal, B. J. Wiatrak, H. K. Kashima et al., « A staging system for assessing severity of disease and response to therapy in recurrent respiratory papillomatosis, Laryngoscope, vol.108, issue.6, pp.935-937, 1998.

N. N. Venkatesan, H. S. Pine, and M. P. Underbrink, Otolaryngol. Clin. North Am, vol.45, issue.3, pp.671-694

R. A. Tasca and R. W. Clarke, Recurrent respiratory papillomatosis, vol.91, pp.689-691, 2006.

W. C. Reeves, S. S. Ruparelia, K. I. Swanson, C. S. Derkay, A. Marcus et al., National registry for juvenile-onset recurrent respiratory papillomatosis, vol.129, pp.976-982, 2003.

C. Go, M. R. Schwartz, and D. T. Donovan, Molecular Transformation of Recurrent Respiratory Papillomatosis: Viral Typing and P53 Overexpression, vol.112, pp.298-302, 2003.

P. M. Reidy, « Integration of Human Papillomavirus Type 11 in Recurrent Respiratory Papilloma-Associated Cancer, The Laryngoscope, vol.114, issue.11, pp.1906-1909

J. Gélinas, J. Manoukian, and E. A. Côté, « Lung involvement in juvenile onset recurrent respiratory papillomatosis: a systematic review of the literature », Int. J. Pediatr. Otorhinolaryngol, vol.72, issue.4, pp.433-452, 2008.

S. Karatayli-ozgursoy, J. A. Bishop, A. Hillel, L. Akst, and S. R. Best, « Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population, Ann. Otol. Rhinol. Laryngol, vol.125, issue.3, pp.235-241, 2016.

V. Gerein, E. Rastorguev, J. Gerein, W. Draf, and J. Schirren, « Incidence, age at onset, and potential reasons of malignant transformation in recurrent respiratory papillomatosis patients: 20 years experience, Otolaryngol Head Neck Surg, vol.132, issue.3, pp.392-394, 2005.

J. Niyibizi, C. Rodier, M. Wassef, and H. Trottier, « Risk factors for the development and severity of juvenile-onset recurrent respiratory papillomatosis: a systematic review, Int. J. Pediatr. Otorhinolaryngol, vol.78, issue.2, pp.186-197, 2014.

F. J. Buchinsky, « Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis, PLoS ONE, vol.3, issue.5, p.2263, 2008.

R. Rabah, W. D. Lancaster, R. Thomas, and L. Gregoire, « Human Papillomavirus-11-associated Recurrent Respiratory Papillomatosis Is More Aggressive Than Human Papillomavirus-6-associated Disease, Pediatr. Dev. Pathol, vol.4, issue.1, pp.68-72, 2001.

M. Zeitels and J. A. , Burns, « Laser applications in laryngology: past, present, and future, Otolaryngol. Clin. North Am, vol.39, issue.1, pp.159-172, 2006.

M. Carifi, D. Napolitano, M. Morandi, and D. Dall'olio, Recurrent respiratory papillomatosis: current and future perspectives, vol.11, pp.731-738, 2015.

S. Schraff, C. S. Derkay, B. Burke, and L. Lawson, « American Society of Pediatric Otolaryngology members' experience with recurrent respiratory papillomatosis and the use of adjuvant therapy, Arch. Otolaryngol. Head Neck Surg, vol.130, issue.9, pp.1039-1042, 2004.

H. Nodarse-cuní, « Interferon alpha-2b as adjuvant treatment of recurrent respiratory papillomatosis in Cuba: National Programme (1994-1999 report), J Laryngol Otol, vol.118, issue.9, pp.681-687, 2004.

G. B. Healy, R. D. Gelber, A. L. Trowbridge, K. M. Grundfast, R. J. Ruben et al., « Treatment of recurrent respiratory papillomatosis with human leukocyte interferon. Results of a multicenter randomized clinical trial, N. Engl. J. Med, vol.319, issue.7, pp.401-407, 1988.

E. De-clercq, J. Descamps, P. Somer, A. Holyacute, and «. , 3-Dihydroxypropyl)adenine: An Aliphatic Nucleoside Analog with Broad-Spectrum Antiviral Activity, Science, vol.200, issue.9, pp.563-565, 1978.

C. S. Derkay, « Current use of intralesional Cidofovir for recurrent respiratory papillomatosis, Laryngoscope, vol.123, issue.3, pp.705-712, 2013.

A. N. Naiman, S. Ayari, R. Nicollas, G. Landry, B. Colombeau et al., « Intermediate-term and long-term results after treatment by Cidofovir and excision in juvenile laryngeal papillomatosis, Ann. Otol. Rhinol. Laryngol, vol.115, issue.9, pp.667-672, 2006.

J. S. Mcmurray, N. Connor, and C. N. Ford, Cidofovir efficacy in recurrent respiratory papillomatosis: a randomized, double-blind, vol.117, pp.477-483, 2008.

R. D. Wemer, J. H. Lee, H. T. Hoffman, R. A. Robinson, and R. J. Smith, « Case of progressive dysplasia concomitant with intralesional Cidofovir administration for recurrent respiratory papillomatosis, Ann. Otol. Rhinol. Laryngol, vol.114, issue.11, pp.836-839, 2005.

F. I. Broekema and F. G. Dikkers, « Side-effects of Cidofovir in the treatment of recurrent respiratory papillomatosis, Eur Arch Otorhinolaryngol, vol.265, issue.8, pp.871-879, 2008.

R. E. Tjon-pian-gi, Safety of intralesional Cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients, vol.270, pp.1679-1687, 2013.

T. Shih, C. Lindley, and . Bevacizumab, an angiogenesis inhibitor for the treatment of solid malignancies, Clin Ther, vol.28, issue.11, pp.1779-1802, 2006.

R. Rahbar, « Role of vascular endothelial growth factor-A in recurrent respiratory papillomatosis, Ann. Otol. Rhinol. Laryngol, vol.114, issue.4, pp.289-295, 2005.

D. J. Rogers, S. Ojha, R. Maurer, and C. J. Hartnick, Use of adjuvant intralesional bevacizumab for aggressive respiratory papillomatosis in children, vol.139, pp.496-501, 2013.

D. R. Sidell, M. Nassar, R. T. Cotton, S. M. Zeitels, and A. De-alarcon, High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis, vol.123, pp.214-221, 2014.

R. Wu, A. L. Abramson, M. J. Shikowitz, A. J. Dannenberg, and B. M. Steinberg, « Epidermal growth factor-induced cyclooxygenase-2 expression is mediated through phosphatidylinositol-3 kinase, not mitogen-activated protein/extracellular signalregulated kinase kinase, in recurrent respiratory papillomas, Clin. Cancer Res, vol.11, pp.6155-6161, 2005.

A. Limsukon, I. Susanto, G. W. Soo-hoo, S. M. Dubinett, and R. K. Batra, « Regression of recurrent respiratory papillomatosis with celecoxib and erlotinib combination therapy, Chest, vol.136, issue.3, pp.924-926, 2009.

B. Bostrom, J. Sidman, S. Marker, T. Lander, and E. D. Drehner, « Gefitinib therapy for life-threatening laryngeal papillomatosis, Arch. Otolaryngol. Head Neck Surg, vol.131, issue.1, pp.64-67, 2005.

J. Ahn, J. A. Bishop, R. B. Roden, C. T. Allen, and S. R. Best, « The PD-1 and PD-L1 pathway in recurrent respiratory papillomatosis, Laryngoscope, vol.128, issue.1, pp.27-32, 2018.

D. L. Young, M. M. Moore, and L. A. Halstead, « The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma, J Voice, vol.29, issue.2, pp.223-229, 2015.

G. R. Dion, « Adjuvant Human Papillomavirus Vaccination for Secondary Prevention: A Systematic Review, JAMA Otolaryngol Head Neck Surg, vol.143, issue.6, pp.614-622, 2017.

I. Ho?evar-bolte?ar, « Human papilloma virus vaccination in patients with an aggressive course of recurrent respiratory papillomatosis, Eur Arch Otorhinolaryngol, vol.271, pp.3255-3262, 2014.

M. Chiril? and S. D. Bolboac?, « Clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis, Eur Arch Otorhinolaryngol, vol.271, issue.5, pp.1135-1142, 2014.

M. Marsico, V. Mehta, and C. Wentworth, « Estimating the disease burden of juvenile onset RRP in the US using large administrative databases -preliminary pilot results, at the International Papillomavirus Conference, 2009.

C. S. Derkay, Task force on recurrent respiratory papillomas. A preliminary report, vol.121, pp.1386-1391, 1995.

K. T. Bieging and L. D. Attardi, « Deconstructing p53 transcriptional networks in tumor suppression, Trends in Cell Biology, vol.22, issue.2, pp.97-106

J. Pflaum, S. Schlosser, and M. Müller, « p53 Family and Cellular Stress Responses in Cancer, Front Oncol, vol.4, p.285, 2014.

D. W. Meek, « Regulation of the p53 response and its relationship to cancer », Biochem. J, vol.469, issue.3, pp.325-346, 2015.

J. K. Mckenney, S. Desai, C. Cohen, and M. B. Amin, « Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens », Am. J. Surg. Pathol, vol.25, issue.8, pp.1074-1078, 2001.

H. Xie, Diagnostic utility of TP53 and cytokeratin 7 immunohistochemistry in idiopathic inflammatory bowel disease-associated neoplasia, vol.27, pp.303-313, 2014.

H. Fu, L. Shao, Q. Wang, T. Jia, M. Li et al., « A systematic review of p53 as a biomarker of survival in patients with osteosarcoma, Tumour Biol, vol.34, issue.6, pp.3817-3821, 2013.

W. Yao, « Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma », Int J Clin Exp Pathol, vol.7, issue.10, pp.7158-7163, 2014.

R. Rabah, W. Sakr, R. Thomas, W. D. Lancaster, and L. Gregoire, « Human papillomavirus type, proliferative activity, and p53: potential markers of aggressive papillomatosis, Arch. Pathol. Lab. Med, vol.124, issue.5, pp.721-724, 2000.

S. Gonfloni, V. Caputo, and V. Iannizzotto, « P63 in health and cancer, Int. J. Dev. Biol, vol.59, pp.87-93, 2015.

C. P. Crum and F. D. Mckeon, « p63 in epithelial survival, germ cell surveillance, and neoplasia, Annu Rev Pathol, vol.5, pp.349-371, 2010.

C. J. Di-como, « p63 expression profiles in human normal and tumor tissues, Clin. Cancer Res, vol.8, issue.2, pp.494-501, 2002.

G. Gualco, L. M. Weiss, and C. E. Bacchi, « Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma », Hum. Pathol, vol.39, issue.10, pp.1505-1510, 2008.

V. Y. Jo and C. D. Fletcher, « p63 immunohistochemical staining is limited in soft tissue tumors, Am. J. Clin. Pathol, vol.136, issue.5, pp.762-766, 2011.

L. L. Muzio, « p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma, Hum. Pathol, vol.36, issue.2, pp.187-194, 2005.

N. Ramer, « Prognostic value of quantitative p63 immunostaining in adenoid cystic carcinoma of salivary gland assessed by computerized image analysis, Cancer, vol.116, issue.1, pp.77-83

R. E. Tjon-pian-gi, « Clinical course of recurrent respiratory papillomatosis: comparison between aggressiveness of human papillomavirus-6 and human papillomavirus-11, Head Neck, vol.37, issue.11, pp.1625-1632, 2015.

A. H. Coons, H. J. Creech, and R. N. Jones, « Immunological Properties of an Antibody Containing a Fluorescent Group, Proceedings of the Society for Experimental Biology and Medicine, vol.47, issue.2, pp.200-202

M. H. Van-regenmortel, « The recognition of proteins and peptides by antibodies, J Immunoassay, vol.21, issue.2-3, pp.85-108, 2000.

M. Werner, A. Chott, A. Fabiano, and H. Battifora, Effect of Formalin Tissue Fixation and Processing on Immunohistochemistry, vol.24, p.1016, 2000.

, Identification de facteurs prédictifs de sévérité des papillomatoses respiratoires récurrentes juvéniles : A propos d'une série de 48 patients

, La papillomatose respiratoire récurrente (PRR) juvénile est caractérisée par la survenue de papillomes malpighiens au niveau des voies aériennes due à l'infection par les HPV 6 et 11

, L'évolution de la maladie reste imprévisible : d'une guérison spontanée à une forme floride potentiellement obstructive et de rares transformations malignes. L'objectif de ce travail est l'identification de critères histologiques prédictifs de la sévérité de la PRR juvénile

. Quarante-huit, Une étude immunohistochimique des papillomes avec les anticorps anti-p16, p53 et p63 a été combinée à une hybridation in situ chromogénique (CISH) reconnaissant les ARNm des HPV 6 et 11. Les marquages immunohistochimiques avec les anticorps anti-p53 et anti-p63 ont fait l'objet d'un comptage avec un logiciel utilisant l'intelligence artificielle. L'intensité de marquage de la CISH a été

. Vingt-quatre-enfants-présentaient-une-prr-sévère, Nous avons mis en évidence une association statistiquement significative entre le caractère sévère de la PRR et le marquage ? 4,5% des cellules avec l'anticorps anti-p53 et ? 30% avec l'anticorps anti-p63 (p=0,001)

, En conclusion grâce à l'utilisation de l'analyse d'image avec l'intelligence artificielle, nous avons mis en évidence une signature immunohistochimique associée à la sévérité de la PRR. La CISH parait également intéressante mais l'étude d'une cohorte plus large est nécessaire

, Mots clés : Papillomatose respiratoire récurrente, HPV de bas risque, CISH, facteurs prédictifs de sévérité

, Severity risk factors identification in juvenile-onset recurrent respiratory papillomatosis: about a 48 patients cohort

, JoRRP) is a condition characterized by the repeated growth of benign exophytic papilloma in the respiratory tract. The course of the disease is still unpredictable: Some children experience spontaneous remission, while others require multiple surgeries due to florid growth, uncommonly the disease may transform into malignant lesions, Juvenile-onset recurrent respiratory papillomatosis

, We defined the severity as an annual rate of interventional endoscopy ? 5, a spread to the lung, a carcinomatous transformation or the death. We conducted immunostaining against p16, p53 and p63 combined with a chromogenic in situ hybridization (CISH) against E6 and E7 transcripts of HPV 6 and 11. Immunostainings against p63 and p53 was analyzed with an artificial intelligence-based software allowing us to count the nuclear staining depending on the strength. CISH staining strength was divided in two categories: 1+ and 2+. Twenty-four patients had serious disease. Staining with p53 antibody ? 4,5% and with p63 antibody ? 30% was associated with severity (p=0,001)

, In conclusion we pointed out with computerized image analysis based on artificial intelligence that our immunostaining signature is associated with severity in JoRRP. CISH might be a promising risk factor to be

, Keywords: juvenile-onset recurrent respiratory papillomatosis, low risk HPV, CISH, severity risk factor, p53, p63, p53, artificial intelligence, computerized image analysis Université Paris Descartes Faculté de Médecine Paris Descartes 15