SARS-CoV-2 impact on oral health: a general view / Impacto del SARS-CoV-2 en la salud oral: una visión general

Abstract Coronavirus disease 2019 (COVID-19) is a new disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. China reported the first case of COVID-19 in December 2019, and a few months later, the World Health Organization declared it as a pandemic. Oral ulcers in adult patients have been associated with COVID-19. However, no cases have yet been documented in children. The angiotensin-converting enzyme-2 (ACE2) receptor has been identified in tissues of the oral cavity. Studies have identified the tongue as the site with the highest expression of ACE2, and the oral epithelium, gingival epithelium, and salivary glands as sites of lesser extent expression. ACE2 expression is lower in children and varies with age. SARS-CoV-2 in saliva has been identified in various studies, which suggests that this could be a useful sample for diagnosis. However, its presence in saliva would indicate the high risk of contagion of this fluid.

Resumen La COVID-19 es una nueva enfermedad causada por el SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo grave). El primer caso de COVID-19 se reportó en China en diciembre de 2019, y unos meses después la Organización Mundial de la Salud la declaró como una pandemia. En pacientes adultos se han asociado úlceras orales a la COVID-19; en niños aún no se han documentado casos. El receptor de la enzima convertidora de la angiotensina 2 (ECA2) se ha identificado en tejidos de la cavidad oral. Los estudios han identificado que la lengua es el sitio con mayor expresión del receptor de la ECA2, y el epitelio bucal, el epitelio gingival y las glándulas salivales lo son en menor medida. La expresión de la ECA2 es menor en los niños y va aumentando con la edad. En diversos estudios se ha identificado el SARS-CoV-2 en la saliva, lo que sugiere que podría ser una muestra útil para el diagnóstico de este virus. Sin embargo, su presencia en saliva indicaría un alto riesgo de contagio de este fluido.

Presencia y Expresión del Receptor ACE2 (Target de SARS-CoV-2) en Tejidos Humanos y Cavidad Oral. Posibles Rutas de Infección en Órganos Orales / Presence and Expression of ACE2 Receptor (Target of SARS-CoV-2) in Human Tissues and Oral Cavity. Possible Routes Infection in Oral Organs

RESUMEN: Un nuevo coronavirus (SARS-CoV-2) ha sido reconocido como el agente etiológico de una misteriosa neumonía originada en Wuhan, China. La OMS ha nombrado a la nueva enfermedad como COVID-19 y, además, la ha declarado pandemia. Taxonómicamente, SARS-CoV-2 pertenece al género de los betacoronavirus junto con SARS-CoV y MERS-CoV. SARS-CoV-2 utiliza la enzima convertidora de la angiotensina 2 (ACE2) como el receptor objetivo para el ingreso en una célula huésped. La expresión de ACE2 en células de tejidos humanos podría indicar un potencial riesgo de reconocimiento por parte del virus y, por ende, ser susceptibles a la infección. Mediante algunas técnicas de laboratorio y de bioinformática, se ha visto una alta presencia de ACE2 en células epiteliales alveolares tipo II de pulmón y en enterocitos del intestino delgado. En la cavidad oral, se ha podido identificar la presencia de ACE2, principalmente, en células epiteliale s de glándulas salivales y células epiteliales de la lengua. Además, se ha reportado la manifestación de algunos síntomas, como sequedad bucal y ambligeustia, los que podrían estar relacionadas con una infección de SARS-CoV-2 en estos órganos. Sin embargo, son necesarios mayores estudios que evidencien esta situación.

ABSTRACT: A novel coronavirus (SARS-CoV-2) has been recognized as a etiologic agent of a mysterious pneumonia originating in Wuhan, China. WHO has named the new disease as COVID-19 and, in addition, has declared it a pandemic. Taxonomically, SARS-CoV-2 belongs to the betacoronavirus genus along with SARS-CoV and MERS-CoV. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the target receptor for entry into a host cell. The expression of ACE2 in cells of human tissues could indicate a potential risk of recognition by the virus and, therefore, be susceptible to infection. Through some laboratory and bioinformatics techniques, high presence of ACE2 has been seen in type II alveolar epithelial cells of the lung and enterocytes of the small intestine. In oral cavity, mainly presence of ACE2 has been identified in epithelial cells of salivary glands and epithelial cells of tongue. In addition, manifestation of some symptoms, such as dry mouth and amblygeustia, have been reported, which could be related to a SARS-CoV-2 infection in these organs. However, further studies are needed to prove this situation.

Epidemiología de la infección oral por VPH en sujetos jóvenes sanos / Epidemiology of oral HPV infection in young healthy individuals

Resumen Introducción: La infección por VPH es la infección viral de transmisión sexual más frecuente, y se encuentra asociada a diversas neoplasias. Objetivo: Describir la epidemiología, historia natural y factores de riesgo asociados a la infección oral por VPH en adultos jóvenes asintomáticos. Métodos: Se realizó un estudio prospectivo de corte longitudinal, que incluyó sujetos sin patología oral, a los que se les tomó una muestra de la mucosa bucal. A todos los sujetos con resultados positivos se les realizó un nuevo muestreo seis meses después. Se identificó la presencia del virus por RPC; los datos demográficos y de conducta sexual fueron obtenidos con una encuesta que respondieron sin intervención del investigador. Resultados: Se recolectaron 102 muestras de sujetos de 18-26 años de edad, 60 (58,8%) correspondieron al sexo masculino. La prevalencia del virus fue de 6,9%; todos los sujetos positivos tenían vida sexual. Las relaciones sexuales entre personas del mismo sexo fue la única variable asociada a la presencia del virus (p < 0,05). A los seis meses, todos los sujetos habían eliminado al virus. Conclusión: La infección oral por VPH es transitoria y está asociada a relaciones sexuales entre personas del mismo sexo, principalmente mujeres que tienen sexo con mujeres.

Background: HPV infection is the most common sexually transmitted viral infection, and is associated with several neoplasms. Aim: To describe the epidemiology, natural history and risk factors associated with oral HPV infection in asymptomatic young adults. Methods: A prospective and longitudinal study was conducted, including subjects without oral pathology, who were sampled from the oral mucosa. All subjects with positive results were re-sampled 6 months later. The presence of HPV was identified by PCR. Demographic and sexual behavior data were obtained with a survey that was responded without the intervention of the researcher. Results: 102 samples were collected from subject of 18-26 years old, 60 (58.8%) were male. The prevalence of the virus was 6.9%; all positive subjects had active sexual life. Same-gender relationships were the only variable associated with the presence of the virus (p < 0.05). At six months all subjects had eliminated the virus. Conclusion: Oral HPV infection is transient and is associated to same-gender relationships, mainly women who have sex with women.

Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil / Papilomavírus humano (HPV) em carcinomas de cavidade oral e orofaringe na região central do Brasil

Abstract Introduction Molecular studies about carcinomas of the oral cavity and oropharynx demonstrate the presence of human papilomavirus genome in these tumors, reinforcing the participation of human papilomavirus in oral carcinogenesis. Objectives This study aimed to determine the prevalence of human papilomavirus and genotype distribution of HPV16 and HPV18 in oral cavity and oropharynx carcinomas, as well as their association with clinical characteristics of the tumors. Methods This is a retrospective study, with clinical data collected from 82 patients. Human papilomavirus detection was conducted on specimens of oral cavity and oropharynx carcinomas included in paraffin blocks. Patients were assisted in a cancer reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of human papilomavirus. Results Among the patients evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78%) and alcohol consumption (70.8%) were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9–36.6) of which 33.3% were HPV16 and 14.3% were HPV18. The presence of lymph node metastases and registered deaths were less frequent in human papilomavirus positive tumors, suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant. Conclusion The results obtained in the present study, with respect to the presence of the high-risk HPV16 and HPV18 genotypes, highlight the importance of human papilomavirus vaccination in the control of oral cavity and oropharynx carcinomas.

Resumo Introdução Estudos moleculares sobre carcinomas da cavidade oral e orofaringe demonstram a presença do genoma do papilomavírus humano (HPV) nesses tumores, o que enfatiza a participação do HPV na carcinogênese oral. Objetivos Determinar a prevalência de HPV e a distribuição genotípica de HPV16 e HPV18 nos carcinomas de cavidade oral e orofaringe, bem como sua associação com as características clínicas dos tumores. Método Estudo retrospectivo, com dados clínicos coletados de 82 pacientes. A detecção de HPV foi feita em amostras de carcinomas de cavidade oral e orofaringe incluídos em blocos de parafina. Os pacientes foram atendidos em um centro de referência para tratamento do câncer, na região central do Brasil, entre 2005 e 2007. Foi usada a reação em cadeia de polimerase (PCR) para a detecção e genotipagem do HPV. Resultados Entre os pacientes avaliados, 78% eram homens. A média de idade do grupo era de 58 anos. Fatores de risco como o tabagismo (78%) e consumo de álcool (70,8%) foram registrados para o grupo. HPV DNA foi detectado em 21 casos (25,6%; IC de 95%, 16,9-36,6), dos quais 33,3% eram HPV16 e 14,3% eram HPV18. A presença de metástases em linfonodos e os óbitos registrados foram menos frequentes em tumores positivos para HPV, o que sugere melhor prognóstico para esses casos; contudo, as diferenças entre os grupos não foram estatisticamente significantes. Conclusão Os resultados obtidos no presente estudo, com respeito à presença de genótipos de alto risco de HPV16 e HPV18, destacam a importância da vacinação para HPV no controle dos carcinomas de cavidade oral e orofaringe.

Higher prevalence and gene amplification of HPV16 in oropharynx as compared to oral cavity

ABSTRACT Objective The objective of this study was to clarify differences regarding HPV16 infection and gene amplification between the oral cavity and oropharynx in healthy individuals. Material and Methods The subjects were 94 healthy asymptomatic individuals (41 males, 53 females; mean age 58.6 years, range 16-97 years) who visited the Department of Oral and Maxillofacial Reconstructive Surgery of the Hiroshima University Hospital from 2014 to 2015. Oral epithelial cells were collected from oral rinse and pharynx gargle samples and placed in saline. The human endogenous retrovirus gene ERV3-1 was used as a reference to estimate the number of human cells in each sample. DNA samples were extracted from approximately 10,000 human cells and tested for HPV16 DNA by PCR using a type-specific primer. Similarly, we analyzed the HPV16 viral copy number in HPV16-positive cases using real-time PCR to examine genomic amplification. Results The percentage of HPV16-positive cases was higher in the gargle (28.7%) as compared to the rinse (16.0%) samples. In the oral rinse samples, males (26.8%) showed a significantly higher rate of HPV16 than females (7.5%) (P=0.021). Importantly, in older subjects (aged 60-89 years), gargle samples showed a significantly higher rate of HPV16 (33.3%) than oral rinse samples (13.7%) (P=0.034). The average number of viral copies was approximately 8 times higher in the gargle than in the oral rinse samples (0.16±0.27 vs. 1.35±1.26 copy numbers per cell), a significant difference (P<0.001). Conclusion Our findings suggest that the oropharynx is more susceptible to HPV16 infection as compared to the oral cavity, while HPV16 gene amplification is also more commonly found in the oropharynx.

Prevalencia del virus papiloma humano en pacientes con diagnóstico de carcinoma escamoso de la cavidad oral / Human papilloma virus prevalence in patients diagnosed with squamous carcinoma oral cavity

Aim: To establish the prevalence of HPV in patients with diagnose of Oral Squamous cell carcinoma, treated in the Instituto nacional del Cáncer in fresh tumoral samples. methods: Cross-sectional study. The inclusion criteria were patients over 18 years, histological diagnosis of Oral Squamous cell carcinoma, that haven’t received any previous cancer treatment, in normal physical and mental conditions. All patients signed an informed consent. Samples consisting of fresh biopsies of lesions with clinical and pathological diagnosis were made. The samples were processed in the Programme of Virology, Faculty of Medicine, Universidad de Chile, through PCR and genotyped by Linear Array® (ROCHE). Results: The prevalence of VPH obtained in this patients was of 9.09% (2/22), corresponding 1 to VPH 56. The positive patients for VPH resulted to be a man of 35 years and a woman of 73 years (9%). Conclusion: The prevalence of HPV in this type of patients was 9.09%, similar than the international publications.

Objetivos: Determinar la prevalencia del virus papiloma humano (VPH) en pacientes con diagnóstico de carcinoma escamoso de la cavidad oral (COCE), atendidos en el Instituto nacional del Cáncer (INCANCER). material y método: Estudio de corte transversal. Criterios de inclusión: pacientes mayores de 18 años, con diagnóstico histológico de COCE, que no hubiesen recibido ningún tratamiento oncológico previo, en condiciones físicas y mentales normales. Todos los pacientes firmaron el consentimiento informado. Se les realizó una entrevista y se tomaron muestras que consistieron en biopsias frescas de lesiones con diagnóstico clínico y anatomopatológico de COCE. Las muestras se procesaron en el Programa de Virología de la Facultad de Medicina de la Universidad de Chile, a través de PCR y se genotipificaron mediante Linear Array® (ROCHE). Resultados: La prevalencia de VPH obtenida en estos pacientes fue de un 9,09% (2/22), correspondiendo 1 a VPH 56. Los pacientes positivos para VPH resultaron ser un hombre de 35 años y una mujer de 73 años (9%). Conclusión: La prevalencia del VPH en este tipo de pacientes fue de 9,09%, similar a las publicaciones internacionales.

Detection of human papillomavirus in dental biofilm and the uterine cervix of a pregnant adolescent / Detecção do papilomavírus humano em biofilme dental e no colo uterino de uma adolescente grávida

CONTEXT: Adolescence and pregnancy are considered to be risk factors for human papillomavirus (HPV) infection. The relationship between this infection in the uterine cervix and oral HPV infection is controversial. CASE REPORT: This report describes a case of a pregnant 16-year-old adolescent who presented HPV infection in the uterine cervix and the mouth. Smears were collected from the cervix and the tongue/palate. Dental biofilm samples were also collected. The microarray technique was used to detect HPV. The HPV 56 subtype was observed in the cervical smear and HPV 6 in dental biofilm. CONCLUSION: In this pregnant adolescent, HPV infection was present in both the cervix and the mouth, but the HPV subtypes infecting these two areas were different.

CONTEXTO: A adolescência e a gestação são consideradas fatores de risco para a infecção pelo papilomavírus humano (HPV). A relação entre essa infecção no colo do útero e na boca num mesmo paciente é controversa. RELATO DE CASO: Descrever o caso de uma adolescente grávida de 16 anos que apresentou a infecção pelo HPV no colo do útero e na boca. Esfregaços foram realizados no colo do útero e em língua/palato. Amostras de biofilme dental também foram coletadas. Para detectar o HPV, foi utilizada a técnica do microarranjo. O HPV 56 foi o subtipo encontrado no esfregaço cervical e o tipo HPV 6 no biofilme dental. CONCLUSÕES: Observamos, nessa adolescente grávida, a presença do HPV na boca e no colo do útero, mas os subtipos virais que infectavam essas duas regiões eram distintos.

Presencia del virus papiloma humano en la cavidad oral: revisión y actualización de la literatura / Presence of human papillomavirus in oral cavity: review and update of literature

El virus del papiloma humano (VPH) forma parte de un grupo de virus ADN heterogéneo llamados papillomaviridae; este virus es causante de múltiples lesiones hiperplásicas, verrucosas y papilomatosas de las células epiteliales de piel y mucosas, existen más de 120 tipos de VPH, de solo 100 se conoce su secuencia genómica completa. Los dos géneros más importantes son los papilomavirus alpha (ð) y los beta (ß), la mayoría de los virus que infectan el área genital pertenecen al género alpha; según sus características clínicas, se pueden subdividir en cutáneos y de mucosa. Si bien las infecciones por este virus son frecuentes en cavidad oral, este campo de la medicina se encuentra en estudio, debido a que la información sobre el tema no es concluyente, es prioritario para el estomatólogo conocer las generalidades acerca del VPH y tratar las lesiones de una manera informada, este virus se asocia a un 35% de los casos de cáncer de cavidad oral, de los cuales el 70% de ellos son de alto riesgo. En México, se tiene estimado que cerca del 43% de los hombres y del 17,5% de las mujeres, todos ellos sanos y sexualmente activos tienen alguna infección por VPH.

The human papillomavirus (HPV) is part of heterogeneous group of DNA viruses called papillomaviridae; this virus causes multiple hyperplastic, papillomatous and warty lesions of epithelial cells of skin and mucosa, there are more than 120 types of HPV, although, the complete genome sequence of only 100 of these is known. The most important types are the alpha papillomavirus (a) and beta (b), most viruses that infect the genital area belong to the alpha type; according to their clinical characteristics, they can be divided in cutaneous and mucosal. HPV infections are common in oral cavity, this field of medicine is currently being studied, considering that the information about this subject is not conclusive, it is a priority for the stomatologist to know the generalities about HPV and treat injuries in an informed manner; this virus is associated to a 35% of cases of oral cancer, of which 70% are considered high risk. In Mexico, it is estimated that about a 43% of men and a 17.5% of women, all of them healthy and sexually active have at least one HPV infection.

Human papilloma virus and oral cancer: narrative review of the literature / Virus papiloma humano y cáncer oral: revisión narrativa de la literatura

The Human Papilloma Virus (HPV) infection is now more common sexually transmitted diseases, with an incidence of 5.5 million worldwide, with 85 percent of the carrier of this virus adult population. Their oncogenic potential and increased oral lesions associated with oral HPV infection have led us to make a narrative of the literature on the role of HPV in oral cancer, especially types 16 and 18. Here we refer to the possible routes of infection, oncogenic mechanisms, both benign and potentially malignant oral lesions associated with the infection, different methods used for detection, prediction and prevention of infection. We stress the importance of the role of the dentist to identify individuals considered high risk and ease of performing detection in the oral cavity, through a quick and easy method as exfoliative cytology.

El Virus Papiloma Humano (VPH) en la actualidad constituye la infección por transmisión sexual más frecuente, presentando una incidencia de 5,5 millones en el mundo, siendo un 85 por ciento de la población adulta portadora de este virus. Su potencial oncogénico y el aumento de lesiones orales asociadas a infección oral por VPH nos han llevado a realizar una narración de la literatura referente al rol del VPH en el cáncer oral, especialmente de los subtipos 16 y 18. Nos referiremos a sus posibles vías de contagio, mecanismos oncogénicos, lesiones orales tanto benignas como potencialmente malignas asociadas a su infección, diferentes métodos utilizados para su detección, pronóstico y prevención de contagio. Destacamos la importancia del rol del odontólogo para identificar individuos considerados de alto riesgo y la facilidad de realizar su detección en la cavidad oral, a través de un método rápido y sencillo como es la citología exfoliativa.

Viral coinfection in the oral cavity of HIV-infected children: relation among HIV viral load, CD4+T lymphocyte count and detection of EBV, CMV and HSV / Co-infecção viral na cavidade bucal de crianças infectadas pelo HIV: relação entre carga viral, contagem de linfócitos T-CD4+ e detecção de EBV, CMV e HSV

A relação entre a infecção pelo HIV e a presença de diferentes tipos de vírus na cavidade bucal foi estudada em 180 crianças HIV-positivo, com idades entre zero e 13 anos de idade, de ambos os sexos. Os exames foram realizados nos Ambulatórios de Aids Pediátrica dos Hospitais São Lucas e de Clínicas, ambos em Porto Alegre, RS, Brasil e no Centro Hospitalar Universitário da Universidade Estadual de Nova Iorque, em Stony Brook (EUA). O objetivo desta pesquisa foi usar a técnica da PCR para detectar a presença dos vírus CMV, EBV e HSV na cavidade bucal desses pacientes, independentemente da presença ou não de manifestações estomatológicas relacionadas aos mesmos. Pode-se concluir que foi alta a freqüência de vírus detectados na cavidade bucal das crianças da amostra através da técnica da PCR e que a contagem média de linfócitos T-CD4+ das crianças com a presença dos vírus encontrava-se próxima da normalidade, enquanto a Carga Viral do HIV encontrava-se elevada.

Manifestaçöes orais induzidas por H.P.V.: revisäo de literatura e relato de caso / Oral manifestations induced by H.P.V.: literature review and case report

A manifestaçäo clínica da infecçäo por Papiloma Vírus Humano (H.P.V.) na cavidade oral tem sido pouco investigada em relaçäo à infecçäo desse vírus na área genital. Sendo a cavidade oral considerada por muitos autores como reservatório e fonte de infecçäo desse vírus, o presente trabalho abordará as manifestaçöes decorrentes do H.P.V. na boca, bem como a etiopatogenia, transmissäo, incidência, métodos de diagnóstico e terapêutica. Será apresentado, em seguida, um caso clínico de Hiperplasia Epitelial Focal decorrente do H.P.V. 13, onde foi realizado o diagnóstico, tratamento e a proservaçäo da paciente