Frecuencia de VPH, expression de p16 y factores de riesgo de leucoplasia oral de pacientes de Córdoba, Argentina

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Gerardo Gilligan
René Panico
Cecilia Di Tada
Andrea Lucca
Mabel Brunotto
Eduardo Piemonte

Resumen

La literatura actual indica que existen resultados heterogéneos en relación a la frecuencia de infección por VPH en leucoplasias, posiblemente debido a diferentes factores. Entre ellos, la una diversa distribución geográfica del virus. El objetivo de este estudio es describir la frecuencia de VPH en pacientes diagnosticados con leucoplasia. Materiales y métodos: Se realizó un estudio de corte transversal en la Facultad de Odontología de la Universidad Nacional de Córdoba. La infección por VPH fue analizada mediante técnica de PCR e inmunomarcación para p16 mediante inmunohistoquímica. Estos resultados fueron analizados a partir de características clínico-demográficas utilizando el test de Fisher y de McNemar. Resultados: se incluyeron 33 pacientes diagnosticados con diferentes tipos de leucoplasia bucal. El genoma de VPH fue detectado mediante PCR en el 48.5% (n=16) de los casos. El genotipo viral de mayor frecuencia fue el VPH16. P16 fue positiva en el 27% (n=9) de los casos. La concordancia entre las técnicas de detección de VPH evidenció pobre o débil concordancia (McNemar test 0.1185). A excepción de la relación entre irritación mecánica crónica y PCR-HPV+ (p=0.00949) y la localización en lengua y PCR-VPH+ (p=0.0366), no se evidenciaron asociaciones estadísticamente significativas entre las variables estudiadas. Conclusiones: La baja frecuencia de VPH en este estudio va en concordancia con otros estudios de nuesta región. La irritación mecánica crónica podría jugar un rol importante en el desarrollo de leucoplasias asociadas al VPH, preferentemente localizadas en el borde de lengua.

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Kumaraswamy K, Vidhya M. Human papilloma virus and oral infections: An update. J Can Res Ther 2011;7:120. https://doi.org/10.4103/0973-https://doi.org/10.4103/0973-1482.829151482.82915.

Sundberg J, Korytowska M, Burgos PM, Blomgren J, Blomstrand L, DE Lara S, et al. Combined Testing of p16 Tumour-suppressor Protein and Human Papillomavirus in Patients With Oral Leukoplakia and Oral Squamous Cell Carcinoma. Anticancer Res 2019;39:1293-300. https://doi.org/10.21873/anticanres.13241.

Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci 2006;110:525-41. https://doi.org/10.1042/ https://doi.org/10.1042/CS20050369CS20050369.

Gilligan GM, Costa MFFG, Moine L, Panico RL, Piemonte ED. Could chronic mechanical irritation facilitate entry of human papillomavirus (HPV) facilitating oral HPV infection? Translational Research in Oral Oncology 2017. https://doi.org/10.1177/2057178X17746799. https://doi.org/10.1177/2057178X17746799

Hormia M, Willberg J, Ruokonen H, Syrjanen S. Marginal Periodontium as a Potential Reservoir of Human Papillomavirus in Oral Mucosa. Journal of Periodontology 2005;76:358-63. https://doi.org/10.1902/ https://doi.org/10.1902/jop.2005.76.3.358jop.2005.76.3.358.

Siegsmund M, Wayss K, Amtmann E. Activation of latent papillomavirus genomes by chronic mechanical irritation. J Gen Virol 1991;72 (Pthttps://doi.org/10.1099/0022-1317-72-11-278711):2787-9. https://doi.org/10.1099/0022-1317-72-11-2787.https://doi.org/10.1099/0022-1317-72-11-2787

Woo S-B, Cashman EC, Lerman MA. Human papillomavirus-associated oral intraepithelial neoplasia. Mod Pathol 2013;26:1288-97. https://doi. https://doi.org/10.1038/modpathol.2013.70 org/10.1038/modpathol.2013.70.

Lerman MA, Almazrooa S, Lindeman N, Hall D, Villa A, Woo S-B. HPV-16 in a distinct subset of oral epithelial dysplasia. Mod Pathol 2017;30:1646-54 https://doi.org/10.1038/modpathol.2017.71 https://doi.org/10.1038/modpathol.2017.71. https://doi.org/10.1038/modpathol.2017.71

Ukpo OC, Flanagan JJ, Ma X-J, Luo Y, Thorstad WL, Lewis JS. Highrisk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. Am J Surg Pathol 2011;35:1343-50. https://doi.org/10.1097/PAS.0b013e318220e59d. https://doi.org/10.1097/PAS.0b013e318220e59d

Mirghani H, Casiraghi O, Amen F, Ben Lakdhar F, He M, Ma X, et al. Diagnosis of HPV-driven head and neck cancer with a single test in routine clinical practice. Mod Pathol n.d.:1518-27.

Smeets S, van der Plas M, Schaaij-Visser T. Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways. IntJ Cancer 2011:1596-1605.

Belobrov S, Cornall A, Young R, Koo K, Angel C, Wiesenfeld D, et al. The role of human papillomavirus in p16-positive oral cancers. Journal of Oral Pathology & Medicine 2018:18-24. https://doi.org/10.1111/jop.12649. https://doi.org/10.1111/jop.12649

Alsabbagh A, Robins TL, Harriman A, Jackson-Boeters L, Darling MR, Khan ZA, et al. Surrogate markers for high-risk human papillomavirus infection in oral epithelial dysplasia: A comparison of p16, Ki-67, and ProExC. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2019;0. https://doi.org/10.1016/j.oooo.2019.09.019. https://doi.org/10.1016/j.oooo.2019.09.019

Yang L-Q, Xiao X, Li C-X, Wu W-Y, Shen X-M, Zhou Z-T, et al. Human papillomavirus genotypes and p16 expression in oral leukoplakia and squamous cell carcinoma. Int J Clin Exp Pathol 2019;12:1022-8.

Cour CD de la, Sperling CD, Belmonte F, Syrjänen S, Verdoodt F, Kjaer SK. Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta-analysis. Head & Neck 2020;42:2975-84. https://doi.org/10.1002/hed.26330 https://doi.org/10.1002/hed.26330. https://doi.org/10.1002/hed.26330

Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, Bagan JV, González-Moles MÁ, Kerr AR, et al. Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis 2020. https://doi.org/10.1111/odi.13704. https://doi.org/10.1111/odi.13704

Piemonte ED, Lazos JP, Brunotto M. Relationship between chronic trauma of the oral mucosa, oral potentially malignant disorders and oral cancer. J Oral Pathol Med 2010;39:513-7. https://doi.org/10.1111/j.1600-0714.2010.00901.x.

Muller S. Oral epithelial dysplasia, atypical verrucous lesions and oral potentially malignant disorders: focus on histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;125:591-602. https://doi.org/10.1016/j. https://doi.org/10.1016/j.oooo.2018.02.012oooo.2018.02.012. https://doi.org/10.1088/1475-7516/2018/02/012

McCord C, Xu J, Xu W, Qiu X, McComb RJ, Perez-Ordonez B, et al. Association of high-risk human papillomavirus infection with oral epithelial dysplasia. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2013;115:541-9. https://doi.org/10.1016/j.oooo.2013.01.020. https://doi.org/10.1016/j.oooo.2013.01.020

Shikova E, Todorova I, Ganchev G, Kouseva-Dragneva V. Detection and Typing of Human Papillomaviruses by PCR. Biotechnology & Biotechnological Equipment 2009;23:877-80. https://doi.org/10.1080/13 https://doi.org/10.1080/13102818.2009.10818562102818.2009.10818562.

Bernard HU, Chan SY, Manos MM, Ong CK, Villa LL, Delius H, et al. Identification and assessment of known and novel human papillomaviruses by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence, and phylogenetic algorithms. J Infect Dis 1994;170:1077-85. https://doi.org/10.1093/infdis/170.5.1077. https://doi.org/10.1093/infdis/170.5.1077

Barnes L, Eveson J, Reichart P, Sidransky D. World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. vol. 85. 2005.

Cour CD de la, Sperling CD, Belmonte F, Syrjanen S, Kjaer SK: Human papillomavirus prevalence in oral potentially malignant disorders: Systematic review and meta-analysis. Oral Diseases 27 (3):431-438; 2021. https://doi.org/10.1111/odi.13322

Criscuolo M-I, Morelatto R-A, Belardinelli P-A, Mosmann J-M, Cuffini C, López de Blanc S-A. Oral Human Papillomavirus: a multisite infection. Med Oral Patol Oral Cir Bucal 2020;25:e425-30. https://doi.org/10.4317/medoral.23462.

Shang Q, Peng J, Zhou Y, Chen Q, Xu H. Association of Human Papillomavirus With Oral Lichen Planus and Oral Leukoplakia: A Metaanalysis. Journal of Evidence Based Dental Practice 2020;20:101485. https://doi.org/10.1016/j.jebdp.2020.101485 https://doi.org/10.1016/j.jebdp.2020.101485. https://doi.org/10.1016/j.jebdp.2020.101485

Sundberg J, Öhman J, Korytowska M, Wallström M, Kjeller G, Andersson M, et al. High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma-A multi-centre study in Sweden,Brazil and Romania. Oral Dis 2021;27:183-92. https://doi.org/10.1111/odi.13510.

Schache AG, Liloglou T, Risk JM, Filia A, Jones TM, Sheard J, et al. Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination. Clin Cancer Res 2011;17:6262-71. https://doi.org/10.1158/1078-0432.CCR-11-0388. https://doi.org/10.1158/1078-0432.CCR-11-0388

Sushma C, Birur NP, Suresh A, Keerthi G, Sunny SP, Shubhasini A, et al. Detection of HPV16 in tissues of oral leukoplakia by polymerase chain reaction and p16 immunohistochemistry: A prospective study.Translational Research in Oral Oncology 2017;2:2057178X17713880. https://doi.org/10.1177/2057178X16685729 https://doi.org/10.1177/2057178X17713880. https://doi.org/10.1177/2057178X17713880

Bhosale PG, Pandey M, Desai RS, Patil A, Kane S, Prabhash K, et al. Low prevalence of transcriptionally active human papilloma virus in Indian patients with HNSCC and leukoplakia. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122:609-618.e7. https://doi.org/10.1016/j.oooo.2016.06.006. https://doi.org/10.1016/j.oooo.2016.06.006

Robinson M, Sloan P, Shaw R. Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing. Oral Oncol 2010;46:492-6. https://doi.org/10.1016/j.oraloncology.2010.02.013. https://doi.org/10.1016/j.oraloncology.2010.02.013

Tomo S, Biss SP, Crivelini MM, de Oliveira SHP, Biasoli ÉR, Tjioe KC, et al. High p16INK4a immunoexpression is not HPV dependent in oral leukoplakia. Arch Oral Biol 2020;115:104738. https://doi.org/10.1016/j. https://doi.org/10.1016/j.archoralbio.2020.104738archoralbio.2020.104738.

Shafti-Keramat S, Handisurya A, Kriehuber E, Meneguzzi G, Slupetzky K, Kirnbauer R. Different Heparan Sulfate Proteoglycans Serve as Cellular Receptors for Human Papillomaviruses. Journal of Virology 2003;77:13125-35. https://doi.org/10.1128/JVI.77.24.13125-13135.2003 https://doi.org/10.1128/JVI.77.24.13125-13135.2003

Gilligan G-M, Panico R-L, Di Tada C, Piemonte E-D, Brunotto M-N. Clinical and Immunohistochemical epithelial profile of non-healing chronic traumatic ulcers. Med Oral Patol Oral Cir Bucal 2020;25:e706-13. https://doi.org/10.4317/medoral.23729.

Perry BJ, Zammit AP, Lewandowski AW, Bashford JJ, Dragovic AS, Perry EJ, et al. Sites of origin of oral cavity cancer in nonsmokers vs smokers: possible evidence of dental trauma carcinogenesis and its importance compared with human papillomavirus. JAMA Otolaryngol Head Neck Surg 2015;141:5-11. https://doi.org/10.1001/jamaoto.2014.2620. https://doi.org/10.1001/jamaoto.2014.2620

Bagan JV, Jimenez Y, Murillo J, Gavaldá C, Poveda R, Scully C, et al. Lack of association between proliferative verrucous leukoplakia and human papillomavirus infection. J Oral Maxillofac Surg 2007;65:46-9. https://doi.org/10.1016/j.joms.2005.12.066.

Della Vella F, Pannone G, Patano A, Ninivaggi R, Del Prete R, Lauritano D, et al. Detection of HPV in oral leukoplakia by brushing and biopsy: prospective study in an Italian cohort. Clin Oral Investig 2020;24:1845-51. https://doi.org/10.1007/s00784-019-03048-y https://doi.org/10.1007/s00784-019-03048-y. https://doi.org/10.1007/s00784-019-03048-y

Matos LL de, Miranda GA, Cernea CR. Prevalence of oral and oropharyngeal human papillomavirus infection in Brazilian population studies: a systematic review. Braz j Otorhinolaryngol 2015;81:554-67. https://doi.org/10.1016/j.bjorl.2015.04.001 https://doi.org/10.1016/j.bjorl.2015.04.001. https://doi.org/10.1016/j.bjorl.2015.04.001

Venezuela RF, Talavera AD, Frutos MC, Kiguen AX, Monetti MS, Sollazo M, et al. Human Papillomavirus (HPV) in oral cavity lesions: comparison with other oral cancer risk factors 2013. https://doi.org/10.5923/j.microbiology.20130306.06.

Steinau M, Reddy D, Sumbry A, Reznik D, Gunthel CJ, Del Rio C, et al. Oral sampling and human papillomavirus genotyping in HIV-infected patients. J Oral Pathol Med 2012;41:288-91. https://doi.org/10.1111/j.1600-0714.2011.01093.x.

Venezuela RF, Kiguen AX, Frutos MC, Cuffini CG. Circulation of human papillomavirus (HPV) genotypes in women from Córdoba, Argentina, with squamous intraepithelial lesions. Rev Inst Med Trop Sao Paulo 2012;54:11-6. https://doi.org/10.1590/s0036-46652012000100003. https://doi.org/10.1590/S0036-46652012000100003