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Abstract Objectives: This study aims to investigate the pattern of immunoexpression of proteins p16, p53 and Ki-67 in RRP, as well as to evaluate its influence on the number of surgeries that patients have undergone to date and to analyze the benefit of immunohistochemistry in this disease. Methods: Clinical-demographic data and tumor samples were obtained from 33 patients with RRP. The expression of proteins p16, p53 and Ki-67 was analyzed by immunohistochemical method. Results: Most patients had already undergone more than one surgery. The p16 marker was negative in 24.2% of the cases, with little positivity in 27.3% of the cases, moderate in 36.4% and intense in 12.1%. The p53 marker was positive in all cases, with little immunoexpression in 39.4% of cases, moderate in 36.4% and intense in 24.2%. The Ki-67 marker showed nuclear positivity in all lesions, although in varying degrees, with a mean proliferative index ±SD (standard deviation) of 51.7±26. Conclusions: The papillomatous lesions had varying degrees of immunoexpression of proteins p16, p53 and Ki-67, but no specific immunohistochemical pattern was observed. It was found, with statistical difference, that the number of surgeries was higher in cases with greater intensity of p53 expression, without correlation with the other markers. The benefit of immunohistochemistry in recurrent respiratory papillomatosis may lie in the prognostic assessment. However, further studies are needed to evaluate the use of this technique for this purpose. Level of evidence:: 4.
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OBJECTIVES: This study aims to investigate the pattern of immunoexpression of proteins p16, p53 and Ki-67 in RRP, as well as to evaluate its influence on the number of surgeries that patients have undergone to date and to analyze the benefit of immunohistochemistry in this disease. METHODS: Clinical-demographic data and tumor samples were obtained from 33 patients with RRP. The expression of proteins p16, p53 and Ki-67 was analyzed by immunohistochemical method. RESULTS: Most patients had already undergone more than one surgery. The p16 marker was negative in 24.2% of the cases, with little positivity in 27.3% of the cases, moderate in 36.4% and intense in 12.1%. The p53 marker was positive in all cases, with little immunoexpression in 39.4% of cases, moderate in 36.4% and intense in 24.2%. The Ki-67 marker showed nuclear positivity in all lesions, although in varying degrees, with a mean proliferative index⯱â¯SD (standard deviation) of 51.7⯱â¯26. CONCLUSIONS: The papillomatous lesions had varying degrees of immunoexpression of proteins p16, p53 and Ki-67, but no specific immunohistochemical pattern was observed. It was found, with statistical difference, that the number of surgeries was higher in cases with greater intensity of p53 expression, without correlation with the other markers. The benefit of immunohistochemistry in recurrent respiratory papillomatosis may lie in the prognostic assessment. However, further studies are needed to evaluate the use of this technique for this purpose. LEVEL OF EVIDENCE: 4.
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Biomarcadores Tumorais , Papiloma , Humanos , Biomarcadores Tumorais/metabolismo , Antígeno Ki-67/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Respiratory recurrent papillomatosis (RRP) is a fatal disease with no known cure. In severe RRP cases, systemic bevacizumab (SB) could be used as adjuvant therapy. OBJECTIVE: This study aims to determine the extent and type of evidence in relation to the clinical outcomes of RRP after SB treatment. METHODS: Participants with RRP of all genders are included in this scoping review. There were no exclusion criteria (country, language, or document type). The information sources included experimental, quasi-experimental, and analytical observational studies. Unpublished data will not be covered, but gray literature was covered. Screening, paper selection, and data extraction were all done by two independent reviewers. This procedure was performed blindly. RESULTS: Of the 175 unique records found, 15 were eligible for inclusion. Fourteen studies were included after applying inclusion and exclusion criteria. Thirty-four patients in these studies came from the United States, India, Germany, Colombia, Argentina, Chile, and Spain. In total, 17 and 34 patients were below 18 years old and were adults respectively. The most commonly reported dose was 10 mg/kg, which was received by 25 (73.5%) patients. According to reports, 58.8% of patients completed the questionnaire. Twelve (35%) patients did not require a repeat surgery. The time interval between surgical procedures has increased for patients who require them. CONCLUSION: SB may be a promissory treatment and control option for RRP. More research is needed to evaluate the efficiency and adverse effects in various populations.
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BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor-related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP. METHODS: A case-control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real-time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program. RESULTS: HPV-6 and HPV-11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994-7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele. CONCLUSION: The G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.
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Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Infecções por Papillomavirus/genética , Polimorfismo de Nucleotídeo Único/genética , Infecções Respiratórias/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene/genética , Haplótipos/genética , Humanos , Lactente , Padrões de Herança/genética , Masculino , México , Pessoa de Meia-Idade , Modelos Genéticos , Projetos Piloto , Adulto JovemRESUMO
OBJECTIVES: This study aimed to compare the prognosis according to age, genotype or human papillomavirus (HPV) variant in patients with recurrent respiratory papillomatosis (RRP). DESIGN: Non-concurrent cohort. PARTICIPANTS: Forty one patients with RRP. SETTING: Tertiary referral hospital. MAIN OUTCOME MEASURES: Disease severity was defined by the number of surgeries performed, and Derkay score at surgeries, obtained from medical records. HPV was detected and genotyped, and HPV-6 variants were also assessed. RESULTS: Fifteen (36.58%) individuals belonged to the juvenile RRP group (JoRRP, less than 18 years), while 26 patients (63.41%) were allocated at the adult group (AoRRP, equal or more than 18 years). JoRRP patients needed, in average, a higher number of surgeries to control the disease than AoRRP patients (mean difference: 3.36). Also, JoRRP patients showed a higher Derkay score at each surgery (mean difference: 3.76). There was no significant difference in the number of surgeries when we compared patients infected with HPV-6 or HPV-11, neither in accordance to HPV-6 variants. Patients with HPV-11 presented a higher mean Derkay score at surgery than those with HPV-6 (mean difference: 4.39); when co-variated by age, we observed that this difference occurred only among JoRRP patients (mean difference: 6.15). CONCLUSIONS: Age of onset of RRP has an important impact on number of surgeries to control disease. Patients with JoRRP and HPV-11 tend to present worse Derkay score at each surgery. HPV genotype among adults and HPV-6 variants had no impact on the outcome of the disease.
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Papillomavirus Humano 11/genética , Papillomavirus Humano 6/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/cirurgia , Prognóstico , Infecções Respiratórias/cirurgia , Adulto JovemRESUMO
Human papillomavirus (HPV) types 6 and 11 are the etiological agents of recurrent respiratory papillomatosis (RRP). We examined the prevalence and distribution of HPVs 6 and 11 genetic variants in juvenile onset (JORRP) and adult onset (AORRP) laryngeal papillomas. Cases of JORRP and AORRP were collected, retrospectively. HPV detection and genotyping were accessed by polymerase chain reaction-sequencing in 67 RRP samples. Overall, the most prevalent HPV-6 variants were from B1 (55.8%) and B3 (27.9%) sublineages, whereas among HPV-11 positive samples A2 (62.5%) variants were predominant. A higher prevalence of HPV-6 B1 was observed in JORRP (83.3% B1 and 16.7% B3), compared with AORRP cases (58.3% B1 and 41.7% B3). HPV-11 A2 variants were more prevalent both in JORRP (57.2%) and in AORRP cases (70.0%). Nevertheless, with the exception that HPV-6 B1 were significantly less likely to recur, there was a lack of association between any particular HPVs 6 or 11 variant and clinicopathological features. Our data do not support an association between HPVs 6 and 11 variability and RRP.
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Variação Genética , Papillomavirus Humano 11/genética , Papillomavirus Humano 6/genética , Neoplasias Laríngeas/virologia , Papiloma/virologia , Infecções por Papillomavirus/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Adolescente , Adulto , Feminino , Genótipo , Humanos , Masculino , Infecções por Papillomavirus/virologia , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES/HYPOTHESIS: To identify factors associated to increased risk of extra-laryngeal spread in pediatric patients with recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Retrospective chart review. METHODS: A retrospective study was conducted evaluating the clinical charts of patients younger than 16 years with histopathologically confirmed RRP treated between January 2014 and December 2018. Characteristics of patients with and without extra-laryngeal disease dissemination were compared. Odds ratios were calculated and multivariate logistic regression analysis was performed. RESULTS: Data from 82 patients were analyzed. Mean age at symptom onset was 42 months. Fifteen (18.29%) patients had extra-laryngeal spread (ELS) at time of diagnosis and in four, the disease continued to spread to other sites. Of 67 patients with disease restricted to the larynx, 17 (25.37%) developed ELS during the disease course. Human papilloma virus (HPV) typing was performed in 49 (59.8%) patients; in 28 (57.1%) HPV subtype 6 was identified and in 21 (42.9%) HPV subtype 11. ELS was found in 11 patients with serotype 11 (52.38%) and in seven patients with serotype 6 (25%) (P = .048). Statistically significant differences for ELS were also found for age at diagnosis younger than 5 years (P = .045), presence of tracheostomy (P = .031), and need for adjuvant therapy (P = .010). CONCLUSIONS: Age at diagnosis of RRP younger than 5 years and presence of tracheostomy were factors related to ELS. A statistically significant association between infection with HPV subtype 11 and ELS were also observed. Adjuvant medication might be considered a protective factor against ELS. Laryngoscope, 131:1652-1656, 2021.
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Doenças da Laringe/diagnóstico , Infecções por Papillomavirus/diagnóstico , Infecções Respiratórias/diagnóstico , Índice de Gravidade de Doença , Adolescente , Antivirais/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Papillomavirus Humano 11/isolamento & purificação , Papillomavirus Humano 6/isolamento & purificação , Humanos , Lactente , Doenças da Laringe/terapia , Doenças da Laringe/virologia , Masculino , Microcirurgia/estatística & dados numéricos , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/virologia , Fatores de Proteção , Infecções Respiratórias/terapia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Fatores de Risco , Traqueostomia/estatística & dados numéricosRESUMO
La papilomatosis respiratoria recurrente (PRR) es la segunda causa más frecuente de disfonía durante la infancia, cuyo agente causal más frecuente es el virus del papiloma humano serotipos 6 y 11. Con el objetivo de analizar las características clínicas y epidemiológicas de la PPR en pacientes pediátricos admitidos en el Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga, se realizó un estudio descriptivo transversal de recolección retrospectiva de datos durante el lapso 2011-2016. Entre las características sociodemográficas se encontró una edad promedio para el momento del diagnóstico de 4,4 ± 2,41 años, siendo los más afectados los preescolares (70%) sin predilección por sexo. Como antecedente prenatal, 90% fue producto de parto vaginal y 30% reportaron asma e infección respiratoria baja. Las características clínicas presentes fueron disfonía (90%), disnea (70%) y estridor (60%) y la localización de las lesiones fueron comisura anterior (100%), repliegues vocales (80% derecho y 90% izquierdo) y vestíbulo (40%). Se reportaron 40% de casos de VPH-6 y 10% de VPH-11. El tratamiento fue quirúrgico en el 100% de los casos, de los cuales 50% requirió una segunda poda y 30% tres podas; 10% de los pacientes ameritaron traqueotomía. Este estudio aporta información sobre la importancia de reconocer tempranamente la disfonía persistente, lo que permite disminuir la demora en el diagnóstico de PRR y facilitar un manejo oportuno con menores tasas de recidiva a largo plazo(AU)
Recurrent respiratory papillomatosis (RRP) is the second most frequent cause of dysphonia during childhood; the most frequent causative agent is human papillomavirus serotypes 6 and 11. In order to describe the clinical and epidemiological characteristics of RRP In pediatric admitted to the Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga, a cross-sectional descriptive study was conducted during the 2011-2016 period. The average age of diagnosis was 4.4 ± 2.41 years, with the highest prevalence in preschool children (70%) and with no sex predilection. 90% of patients were product of vaginal delivery and 30% reported asthma and low respiratory infection. The clinical features present were dysphonia (90%), dyspnea (70%) and stridor (60%); location of the lesions were anterior commissure (100%), vocal folds (80% right and 90% left) and vestibule (40%). 40% of patients reported HPV-6 and 10% HPV-11. Treatment was surgical in 100% of cases of which 50% required a second pruning and 30% three pruning; 10% needed a tracheotomy. This study provides information on the importance of early recognition of persistent dysphonia allowing to reduce diagnosis delay of RRP and facilitate timely management with lower rates of long-term recurrence(AU)
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Humanos , Masculino , Feminino , Pré-Escolar , Papiloma/fisiopatologia , Papillomaviridae , Doenças Respiratórias/complicações , Verrugas , Neoplasias Laríngeas , Disfonia/etiologia , Otolaringologia , Pediatria , Qualidade de Vida/psicologia , Doenças RespiratóriasRESUMO
La papilomatosis respiratoria recurrente es una neoplasia benigna infrecuente que, comúnmente, afecta la vía aérea superior con predilección por la laringe. El compromiso traqueobronquial aislado es muy raro. El diagnóstico y el tratamiento de esta enfermedad constituyen un desafío, debido a su manifestación clínica inespecífica y su naturaleza recurrente. Se presenta a un varón de 6 años con diagnóstico de asma refractario al tratamiento, sin historia ni evidencia de papilomatosis laríngea. El examen endoscópico reveló papilomatosis traqueobronquial extensa, y la tomografia computada, compromiso pulmonar. Recibió terapia adyuvante con bevacizumab endovenoso, con muy buena respuesta. Se alerta a los pediatras para considerar esta rara neoplasia traqueobronquial en todo niño con síntomas de asma atípicos o que no mejoran con el tratamiento médico convencional.
Recurrent respiratory papillomatosis is an infrequent benign neoplasm that commonly affects the upper airway with a predilection for the larynx. Isolated tracheobronchial involvement is very rare. Diagnosis and treatment of this disease is a challenge due to its non-specific clinical manifestation and its recurrent nature. We present a 6-year-old male with a diagnosis of asthma refractory to treatment, without history or evidence of laryngeal papillomatosis. The endoscopic examination revealed extensive tracheobronchial papillomatosis and the computed tomography, pulmonary involvement. He received adjuvant therapy with intravenous Bevacizumab with very good response. We alert pediatricians to consider this rare tracheobronchial neoplasm in all children with atypical asthma symptoms or in those who do not improve with conventional medical treatment.
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Humanos , Masculino , Criança , Papiloma , Doenças Respiratórias , Criança , BevacizumabRESUMO
Recurrent respiratory papillomatosis is an infrequent benign neoplasm that commonly affects the upper airway with a predilection for the larynx. Isolated tracheobronchial involvement is very rare. Diagnosis and treatment of this disease is a challenge due to its non-specific clinical manifestation and its recurrent nature. We present a 6-year-old male with a diagnosis of asthma refractory to treatment, without history or evidence of laryngeal papillomatosis. The endoscopic examination revealed extensive tracheobronchial papillomatosis and the computed tomography, pulmonary involvement. He received adjuvant therapy with intravenous Bevacizumab with very good response. We alert pediatricians to consider this rare tracheobronchial neoplasm in all children with atypical asthma symptoms or in those who do not improve with conventional medical treatment.
La papilomatosis respiratoria recurrente es una neoplasia benigna infrecuente que, comúnmente, afecta la vía aérea superior con predilección por la laringe. El compromiso traqueobronquial aislado es muy raro. El diagnóstico y el tratamiento de esta enfermedad constituyen un desafío, debido a su manifestación clínica inespecífica y su naturaleza recurrente. Se presenta a un varón de 6 años con diagnóstico de asma refractario al tratamiento, sin historia ni evidencia de papilomatosis laríngea. El examen endoscópico reveló papilomatosis traqueobronquial extensa, y la tomografia computada, compromiso pulmonar. Recibió terapia adyuvante con bevacizumab endovenoso, con muy buena respuesta.Se alerta a los pediatras para considerar esta rara neoplasia traqueobronquial en todo niño con síntomas de asma atípicos o que no mejoran con el tratamiento médico convencional.