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The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.
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Objective: To investigate the frequencies and bacterial load of three species of periodontal bacteria in samples from oropharyngeal cancer patients versus healthy individuals. Study design: This is a case-control study based on biopsies collected from tumor tissues obtained from patients with oropharyngeal squamous cell carcinoma between 2016 and 2017 and shed oral mucosal epithelial cells that were collected from controls using the Cepimax® brush, carrying out several brushings towards the posterior third edge of the tongue and the cheek. Porphyromonas gingivalis, Tannerella forsythia and Prevotella intermedia detection and absolute quantification was determined through q-PCR. Statistical analysis included a U- test, X 2 , Fisher's exact test, odds ratio (OR) and Conditional logistic regression analysis and unconditional regression analysis (p < 0.05). Results: A total of 48 donors older than 55 years old participated in this study. The population was distributed into 24 patients (cases) and 24 controls. A robust association was established in cases and controls with significance regarding Prevotella intermedia (OR: 15.00) and Porphyromonas gingivalis (OR:11.00). In the comparison between the amount of each bacteria in the groups, P. intermedia showed a higher bacterial load in oropharyngeal cancer patients (p = 0.04). However, multivariate analysis adjusted to the presence of different bacteria and the diverse confounding variables did not reveal significant differences for oropharyngeal cancer association. Conclusion: P. gingivalis and P. intermedia were detected more frequently in the group of patients with cancer. The bivariate analysis of the bacterial load evidenced significant differences for Prevotella intermedia, suggesting that it could be associated with oropharyngeal cancer.
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Highly oncogenic human papillomavirus (HPV) is well known to be associated with and a risk factor for various types of oral carcinomas such as oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate and describe the HPV-induced OSCC prevalence and genotyping in the city of Belém, northern Brazil. This cross-sectional study features 101 participants who attended an oral pathology referral center in a dental college looking for diagnoses of oral lesions (OL). After signing the consent term and meeting the inclusion criteria, all participants went through a sociodemographic and epidemiological questionnaire. Then, OL were collected by excisional or incisional biopsy depending on OL size; after that, OL tissues were preserved in paraffin blocks to histopathological diagnoses. Afterwards, paraffin blocks were divided into benign and malignant/premalignant lesions based on the classification of potentially malignant disorders of the oral and oropharyngeal mucosa. Then, the paraffin blocks had DNA extraction performed by the ReliaPrep FFPE gDNA Miniprep method in order to identify HPV DNA of high oncogenic risk and low oncogenic risk. Then, the viral DNA was amplified and typed using the Inno-Lipa genotyping Extra II method, and the collected data were analyzed by Chi-square and G-tests. In total, 59/101 (58.4%) OL were malignant/premalignant lesions, of which OSCC was the most prevalent with 40/59 (67.7%) and 42/101 (41.6%) benign lesions. The most common area of OL incidence was upper gingiva 46/101 (45.5%). Regarding HPV DNA detection, approximately 27/101 (26.7%) had positive results; of these, 17/59 (28.8%) were malignant/premalignant lesions, and the most prevalent genotypes detected were 16, 18, 52 and 58, while among benign lesions, 10/42 (66.6%) had HPV-positive results, and the most prevalent genotypes detected were 6, 11 and 42. Age range was the only risk factor with a significant association between HPV and OSCC presence (p-value: 0.0004). A correlation between OSCC and oral HPV among analyzed samples could not be demonstrated in our small cohort.
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Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival.
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High-risk human papillomaviruses (HR-HPV) are the causal agents of an important subset of oropharyngeal cancers that has increased considerably in incidence in recent years. In this study, we evaluated the presence of HPV in 49 oropharyngeal cancers from Chilean subjects. The presence of HPV DNA was analyzed by conventional PCR, the genotypes were identified through sequencing, and the expression of E6/E7 transcripts was evaluated by a reverse transcriptase polymerase chain reaction (RT-PCR). Additionally, to determine p16 expression-a surrogate marker for oncogenic HPV infection-a tissue array was constructed for immunohistochemistry (IHC). HPV was detected in 61.2% of oropharyngeal carcinomas, the most prevalent genotype being HPV16 (80%). E6 and E7 transcripts were detected in 91.6% and 79.1% of the HPV16-positive specimens, respectively, demonstrating functional HPV infections. Furthermore, p16 expression was positive in 58.3% of cases. These findings show a high prevalence of HR-HPV in oropharyngeal tumors from Chile, suggesting the necessity of additional studies to address this growing public health concern.
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Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Alphapapillomavirus/genética , Chile/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Viral/análise , DNA Viral/genética , Humanos , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/metabolismo , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/metabolismo , RNA Viral/genéticaRESUMO
Abstract Introduction The prevalence of oropharyngeal squamous cell carcinoma (OSCC) related to Human Papillomavirus (HPV) is rising in the whole world. Objective To access the prevalence and temporal trend of HPV infection in oropharyngeal cancer by analyzing the expression of the p16 protein. Methods We conducted a transversal study in a Brazilian reference oncology center. The sample consisted of 254 patients with OSCC. The analyzed period was from 2013 to 2017. All patients underwent p16 immunohistochemistry analysis. Results The overall prevalence of HPV-related OSCC was of 31.9%. During the analyzed period, we observed a trend of increasing rates of OSCC that marked positive for p16 immunohistochemistry. The annual prevalence of p16-positive cases was of 20.6% in 2013, 23.9% in 2014, 33.3% in 2015, 38.3% in 2016, and 34.2% in 2017. Most of the patients were stage III and IV (84%). Female patients (odds ratio [OR] = 2.43; 95% confidence interval [CI]: 1.003-5.888; p = 0.049) and younger patients (OR = 2.919; 95%CI: 1.682-5.067; p < 0.005) were associated with a higher risk of HPV-related OSCC. Tobacco consumption had a proportional lower risk of HPV-related OSCC (OR = 0.152; 95%CI: 0063-0.366; p < 0.005). Conclusion We observed an increasing prevalence of HPV-related OSCC in a specialized cancer hospital in Brazil.
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Introduction The prevalence of oropharyngeal squamous cell carcinoma (OSCC) related to Human Papillomavirus (HPV) is rising in the whole world. Objective To access the prevalence and temporal trend of HPV infection in oropharyngeal cancer by analyzing the expression of the p16 protein. Methods We conducted a transversal study in a Brazilian reference oncology center. The sample consisted of 254 patients with OSCC. The analyzed period was from 2013 to 2017. All patients underwent p16 immunohistochemistry analysis. Results The overall prevalence of HPV-related OSCC was of 31.9%. During the analyzed period, we observed a trend of increasing rates of OSCC that marked positive for p16 immunohistochemistry. The annual prevalence of p16-positive cases was of 20.6% in 2013, 23.9% in 2014, 33.3% in 2015, 38.3% in 2016, and 34.2% in 2017. Most of the patients were stage III and IV (84%). Female patients (odds ratio [OR] = 2.43; 95% confidence interval [CI]: 1.003-5.888; p = 0.049) and younger patients (OR = 2.919; 95%CI: 1.682-5.067; p < 0.005) were associated with a higher risk of HPV-related OSCC. Tobacco consumption had a proportional lower risk of HPV-related OSCC (OR = 0.152; 95%CI: 0063-0.366; p < 0.005). Conclusion We observed an increasing prevalence of HPV-related OSCC in a specialized cancer hospital in Brazil.
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INTRODUCTION: Oropharyngeal cancer is characterized by high morbidity and mortality. Prognostic factors for this cancer are therefore useful to predict overall survival and may provide additional therapeutic targets. OBJECTIVE: To evaluate the 5-year overall survival and prognostic factors for oropharyngeal squamous cell carcinoma. METHODS: Retrospective cohort (2008-2018) of a cancer referral center. The population of the study was a hospital-based cohort consisting of patients diagnosed with oropharyngeal cancer who underwent surgery and/or adjuvant therapy (radio- and/or chemotherapy). RESULTS: A total of 253 patients with oropharyngeal squamous cell carcinoma were analyzed. The mean age was 59.8 ± 11.9 years and there was a male predominance (81.8%). Smoking and alcohol consumption were found in 88.0% and 84.2% of the sample, respectively. The combination of radiotherapy and chemotherapy was the treatment modality in 42.7% of the sample, followed by surgery combined with radio- and chemotherapy in 15.8%. There were 143 deaths (events), the mean survival was 11.55 ± 9.69 months, and the 5-year overall survival rate was 1.1%. Overall survival was lower for clinical stage III/IV (p < 0.001), HPV p16-negative status (p = 0.019), and an interval > 4 weeks between diagnosis and the beginning of treatment (p < 0.007). CONCLUSION: Among the prognostic factors analyzed in this cohort, p16-negative status as a poor prognostic indicator and tumor stage III/IV and an interval longer than 4 weeks between diagnosis and the beginning of treatment were significantly associated with lower overall survival.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Idoso , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/cirurgia , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Resumen El carcinoma escamoso de orofaringe (CEOF) ha tenido un aumento en su incidencia en las últimas décadas, explicándose por el aumento sustancial de su tipo relacionado con el virus papiloma humano (VPH). Existen diferencias clínicas y pronósticas entre los dos grupos de CEOF según su relación etiológica con VPH. Por un lado, los relacionados con VPH se presentan en una población más joven, con menos prevalencia de tabaquismo y consumo de alcohol; además de presentar un tamaño pequeño del tumor primario, con un compromiso linfonodal temprano. Además, aquellos relacionados con VPH presentan un mejor pronóstico que su contraparte no relacionada con el virus, presentando en algunos estudios hasta un 58% menos riesgo de muerte independiente de la modalidad de tratamiento. Actualmente, el sistema de clasificación TNM en su 8va edición presenta un sistema diferente de clasificación y etapificación para ambos grupos. A pesar de aquello, a la fecha el tratamiento habitual no difiere entre ambos, lo que ha llevado a la realización de estudios que buscan responder si la deintensificación de la terapia en aquellos grupos relacionados con VPH y con bajo riesgo de metástasis a distancia, mantendría los buenos resultados oncológicos, disminuyendo las complicaciones a corto y largo plazo asociadas al tratamiento. Sin embargo, aún no existe evidencia que avale consistentemente esta práctica. Finalmente, la prevención primaria a través de la vacuna contra VPH es un elemento prometedor, sin embargo, no existe evidencia que confirme su utilidad.
Abstract Oropharyngeal squamous cell carcinoma (OPSCC) has suffered an increase in its incidence in recent decades, explained by the increase in its type related to the human papilloma virus (HPV). There are clinical and prognostic differences between the two groups of OPSCC according to their etiological relationship with HPV. On the one hand, those related to HPV appear in a younger population, with a lower prevalence of smoking and alcohol consumption; in addition to presenting a small size of the primary tumor, with early lymph node involvement. Furthermore, those related to HPV have a better prognosis than their non-virus counterpart, presenting in some studies up to 58% less risk of death, independent of treatment used. Currently, the TNM classification system in its 8th edition presents a different classification for both groups. Despite this, the treatment does not differ between the two, which has led to studies that seek to answer whether the de-escalation of therapy in the group associated to HPV and with a low risk of distant metastasis would maintain the reported good oncological results, reducing early and long-term complications associated with treatment, however, there is still no evidence to support its use. Finally, primary prevention through the HPV vaccine is a promising element, however there is no evidence to confirm its usefulness.
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Timely diagnosis and treatment of oral and oropharyngeal cancers are central for the patient's survival. Our objective was to document the impact of the COVID-19 pandemic on the rate of hospitalizations due to these cancers in Brazil's National Health System (SUS). The number of hospitalizations by these cancers during the first periods of the pandemic-and between the same period of 2016 to 2019-was retrieved from the SUS Hospital Information System. We compared hospitalization rates between pre- and pandemic periods, by State. The hospitalization rate for oral and oropharyngeal cancer during the pandemic was lower than that of the same period of previous years. The decline between 2019 and 2020 was of 49.3%, reaching 60% in the North. The reduction in hospitalization during an extended period suggests that oral and oropharyngeal cancer care will be postponed, with potentially detrimental impact on survival.
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COVID-19 , Neoplasias Orofaríngeas , Brasil/epidemiologia , Hospitalização , Humanos , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/terapia , Pandemias , SARS-CoV-2RESUMO
Oropharyngeal squamous cell carcinoma (OSCC) is a fatal and highly incident disease. Although tobacco and alcohol consumption are the main risk factors associated with OSCC, a recent significant increase in OSCC HPV16 positive cases in high-income countries has been observed. However, it is not clear whether this change is also present in low- and middle-income countries. In this study, we evaluated HPV16 prevalence in 346 OSCC cases diagnosed in the largest Brazilian oncology public hospital by using the combination of two techniques, HPV16 E6 detection by qPCR and p16 immunohistochemistry. In total, 11.9% of cases were HPV16 E6 positive, 9.2% were p16 positive and 6.1% were positive in both analyses. There was a predominance of keratinizing-SCC, with only four HPV-positive cases showing basaloid-like or non-keratinizing-SCC. HPV infection had no impact on disease-free or overall survival, while alcohol use was an independent prognostic factor for overall survival. Most cases reported a high frequency of tobacco (94.6%) and alcohol consumption (88.2%), were of low education level, and typically presented at advanced clinical stages, indicating that the profile of Brazilian OSCC patients has not changed.
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Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/epidemiologia , Prevalência , Proteínas Repressoras/genética , Estudos RetrospectivosRESUMO
PURPOSE: Transoral robotic surgery (TORS) is one of the main treatment options for non-locally advanced primary oropharyngeal cancer in the United States. However, its use is more limited in countries with a low incidence of human papillomavirus (HPV), such as Spain, in patients with advanced disease, and as salvage surgery. To shed light on the use and potential benefit of TORS in Spanish patients, we analyzed the functional and oncologic outcomes of TORS as both primary and salvage surgery in a primarily HPV-negative population which is representative of oropharyngeal squamous cell carcinoma (OPSCC) patients in Spain. MATERIAL AND METHODS: This is a retrospective analysis of prospectively collected data on OPSCC patients treated with TORS at our center between February 2017 and February 2019. RESULTS: Fifty-four OPSCC patients were included; 79.6% were males and 80.5% were HPV negative. Median age was 62 years. Primary surgery was performed on 73.7% (48.1% stage I-II; 51.9% stage III-IV) and salvage surgery on 25.9% of patients. Positive margin rates were 4.3% for T1-2 and 25.8% for T3-4. None of the stage I-II patients and 27.7% of stage III-IV patients required adjuvant treatment. Reconstructive surgery was performed in 19.2% of all patients. Normal swallowing was achieved in 92.7% of patients at 6 months after surgery. 1- and 2-year survival rates for all patients were 94.5% and 89%, respectively. The overall complication rate was 16.1%. Bleeding occurred in 11.5% of patients. Longer hospitalization time was associated with surgical complications (P = 0.03) and reconstructive surgery (P = 0.03) but not with salvage surgery. CONCLUSION: TORS is a safe and effective treatment for HPV-negative T1-2 OPSCC patients. The positive margin rate was worse in T3-4 patients, indicating the need for careful patient selection in this subgroup.
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Neoplasias Orofaríngeas/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus , Deglutição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca , Resultados Negativos , Neoplasias Orofaríngeas/mortalidade , Estudos Retrospectivos , Terapia de Salvação/estatística & dados numéricos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidadeRESUMO
Abstract Oral and oropharyngeal cancer is considered a public health problem in several countries due to its high incidence and mortality rate. Objective: This study aimed to analyze oral and oropharyngeal cancer mortality in Uruguay from 1997 to 2014 by age, sex and country region. Methodology: A time series ecological study using secondary data was performed. Data on mortality due to oral and oropharyngeal cancers were obtained from the Vital Statistics Department of Uruguay's Ministry of Public Health. Results: The cumulative mortality rate due to oral and oropharyngeal cancer over the study period was of 19.26/100,000 persons in women and 83.61/100.000 in men, with a mean annual rate of 1.75/100,000 in women and 7.60/100,000 in men. Mortality rate from both sites during the study period was 4.34 times higher in men than in women. Malignant neoplasms of other parts of the tongue and base of tongue showed the highest mortality rate. The means of the annual coefficients of deaths were higher for the age groups between 50 and 69 years. Higher mortality rates of oral and oropharyngeal cancer were observed in Artigas (4.63) and Cerro Largo (3.75). Conclusions: Our study described a high mortality rate for oral and oropharyngeal cancer in Uruguay from 1997 to 2014. According to the country's health department, men, tongue cancer, and oral cavity had higher mortality rates, with some variation. Prevention strategies with control of risk factors and early diagnosis are necessary to improve survival in the Uruguayan population.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Orofaríngeas/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Fatores de Tempo , Uruguai/epidemiologia , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Neoplasias Orofaríngeas/patologia , Incidência , Fatores de Risco , Distribuição por Sexo , Distribuição por Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
A better understanding of the clinical and molecular features of oropharyngeal squamous cell carcinomas (OPSCC) may help in the development of strategies for a better patient management, improving survival rates. This retrospective study conducted a clinical and molecular characterization of surgically treated OPSCC samples. Paraffin-embedded samples from a series of cases were screened for high-risk (HR) human papillomavirus (HPV) infection, methylation of a 5-gene panel, p53 expression, and TP53 mutation. The study was conducted at Barretos Cancer Hospital. Twenty-five surgically treated OPSCC with available tissue were included in the study. Samples were classified according to HPV status and molecular features and some of these characteristics were associated to clinical data. Twenty percent of the cases were HR-HPV positive and 62.5% presented TP53 mutations. DAPK hypermethylation was associated with HPV status (p = 0.023), while methylated CCNA1 was inversely related to TP53 mutations in primary tumors (p = 0.042) and associated with a better disease-free survival (22.3% vs. 100.0%; p = 0.028) and overall survival (8.0% vs. 100.0%; p = 0.012). The results show differences regarding molecular and clinical characteristics in the oropharynx cases identified that should be validated in more cases to confirm whether these differences are able to classify patients according to outcome and help in a more thorough patient management.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Metilação de DNA , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Viral , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genéticaRESUMO
OBJECTIVES: To identify potential molecular drivers associated with prognosis and response to treatment in advanced oropharyngeal squamous cell carcinomas (OPSCC). MATERIALS AND METHODS: Thirty-three OPSCC biopsies from untreated Brazilian patients were evaluated for human papilloma virus genotyping, genome wide copy number alterations and gene expression profiling. Data were integrated using CONEXIC algorithm. Validation with TCGA dataset and confirmation by RT-qPCR of candidate genes were performed. RESULTS: High-risk HPV positive cases, detected in 55% of advanced OPSCC, were associated with better outcome. Losses of 8p11.23-p11.22, 14q11.1-q11.2 and 15q11.2, and gains of 11q13.2 and 11q13.2-q13.3 were detected as recurrent alterations. Gains of 3q26.31 and 11q13.2 and losses of 9p21.3 were exclusively detected in HPV-negative tumors. Two clusters of expression profiles were observed, being one composed mostly by HPV positive cases (83%). HPV-positive enriched cluster showed predominantly immune response-related pathways. Integrative analysis identified 10 modulators mapped in 11q13, which were frequently cancer-related. These 10 genes showed copy number gains, overexpression and an association with worse survival, further validated by TCGA database analyses. Overexpression of four genes (ORAOV1, CPT1A, SHANK2 and PPFIA1) evaluated by RT-qPCR confirmed their association with poor survival. Multivariate analysis showed that PPFIA1 overexpression and HPV status are independent prognostic markers. Moreover, SHANK2 overexpression was significantly associated with incomplete response to treatment. CONCLUSION: The integrative genomic and transcriptomic data revealed potential driver genes mapped in 11q13 associated with worse prognosis and response to treatment, giving fundamentals for the identification of novel therapeutic targets in OPSCC.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Cromossomos Humanos Par 11 , Oncogenes , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/terapia , Resultado do Tratamento , Proteínas Adaptadoras de Transdução de Sinal/genética , Alphapapillomavirus/isolamento & purificação , Carcinoma de Células Escamosas/virologia , Mapeamento Cromossômico , Feminino , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Neoplasias Orofaríngeas/virologia , Prognóstico , TranscriptomaRESUMO
Resumen El Virus del Papiloma Humano (VPH) es una enfermedad diagnóstico frecuente, transmitida por contacto entre piel y mucosas. Se han descrito múltiples relaciones etiológicas con neoplasias en órganos del sistema genital y reproductor y a nivel de cabeza y cuello. Éste se ha agrupado y caracterizado mediante análisis filogenéticos y en su secuencia de nucleótidos y aminoácidos. EL VPH progresa por las capas de epitelio de piel o mucosa induciendo malignización celular. El diagnóstico se realiza mediante diversas técnicas de PCR o de hibridación in situ. El carcinoma orofaríngeo es una patología neoplásica con una presentación clínica variada. Su asociación a VPH es inmunohistoquímicamente detectable, y se asocia a una presentación más frecuente en jóvenes, en hombres, con una localización anatómica mejor definida, y con una expresión clínica más florida y temprana. Actualmente se ha documentado un incremento en los casos de carcinoma orofaríngeo a pesar del descenso de su principal factor de riesgo; el tabaquismo. Su incidencia y mortalidad continúan siendo relativamente bajas en comparación con otros tumores en cabeza y cuello. Este incremento se ha asociado etiológicamente a la infección de VPH con subtipos de mayor riesgo de malignidad como el VPH 16 y 18. A nivel nacional existen diferencias estadísticas con respecto a los datos foráneos, sin embargo la cantidad de estudios realizados en nuestra población y los sesgos asociados al subregistro de la enfermedad son un factor importante a tomar en cuenta. Es necesario realizar una mayor cantidad de estudios en la población costarricense para determinar el comportamiento real de esta enfermedad y su relación etiológica con el carcinoma de orofaringe en nuestro país.
Abstract The Human Papilloma Virus (HPV) is a frequently diagnosed sexually transmitted disease, transmitted by contact between skin and mucous membranes. There are multiple etiological relationships between HPV infections and neoplasms in organs of the reproductive and genital system and at head and neck. Those belonging to HPV have been grouped and characterized by phylogenetic analysis and by its sequence of nucleotides and amino acids. HPV progresses through the layers of skin or mucosal epithelium inducing malignant transformation in these cells. The diagnosis of this infection is performed using various techniques of PCR and in situ hybridization. Oropharyngeal carcinoma is a neoplastic disease with a varied clinical presentation. Its association with HPV is detectable by immunohistochemic methods. It's also associated more frequent with young people, men, presentation with a better defined anatomic location and an earlier clinical expression. Currently it has been documented an increase in cases of oropharyngeal carcinoma despite the fall of their main risk factor; smoking. Its incidence and mortality continue to be relatively low in comparison with other head and neck tumors. This increase has etiologically been associated with HPV infection; and with subtypes of increased risk of malignancy such as HPV 16 and 18; as with changes in the behavior of the disease. National statistics differ from the foreign data, however the low amount of studies in our population and the biases associated with underreporting of the disease are an important factor to take into account. It is necessary to perform a greater number of studies in the Costa Rican population to determine the actual behavior of this disease and its etiological relation to carcinoma of the oropharynx.
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Humanos , Neoplasias Orofaríngeas/complicações , Infecções por Papillomavirus/patologia , Neoplasias de Cabeça e Pescoço/complicaçõesRESUMO
BACKGROUND: The purpose of this current research was to clarify for the scientific community the trends of tongue cancer epidemiology in Brazil. METHODS: The data came from Population Based Cancer Registries, Hospital Cancer Registries, and Mortality Information System from 2000 to 2014. RESULTS: The age-adjusted incidence rate are increasing in both men and women for base of tongue cancer and for other and unspecified parts of the tongue in women, and decreasing in men for other and unspecified parts of the tongue. The majority of cases were diagnosed at clinical stages III and IV. The mortality rate remained relatively stable in both men and women in the period studied. CONCLUSION: The increase in age-adjusted incidence rate for tongue cancers (except for other and unspecified parts of the tongue in men), with most patients over 50 years of age, with low education levels, and advanced disease reinforces the need for interventions that address access to health promotion resources and medical care in Brazil.
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Neoplasias da Língua/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Brasil/epidemiologia , Carcinoma/epidemiologia , Carcinoma/patologia , Carcinoma/terapia , Uso de Medicamentos/estatística & dados numéricos , Feminino , Glossectomia/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Radioterapia/estatística & dados numéricos , Sistema de Registros , Distribuição por Sexo , Neoplasias da Língua/patologia , Neoplasias da Língua/terapiaRESUMO
To determine mortality rates for oropharyngeal cancer according to the Human Development Index (HDI) per district in the Metropolitan Region (RM), Santiago, Chile, between 2002 and 2014. Materials and Methods: an ecological study was carried out. The sample corresponded to individuals over 45 years, from the Metropolitan Region, with oropharyngeal cancer as cause of death, as registered in the Chilean National Institute of Statistics (INE). The HDI was classified into three categories: "medium" (8 districts), "high" (18 districts) and "very high" (25 districts). The crude and adjusted mortality rates were calculated for each year and period. Results: the oropharyngeal cancer adjusted mortality rate for the chosen period was 3.98 deaths per 100,000 inhabitants. The specific mortality rate from oropharyngeal cancer in the "medium" HDI category was 4.01; in the "high" DHI category, 4.42; and in the "very high" HDI category, 3.79. Conclusion: mortality from oropharyngeal cancer was higher in the "medium" HDI category between 2002 and 2014.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Chile/epidemiologia , Incidência , Distribuição por Sexo , Distribuição por Idade , Estudos EcológicosRESUMO
Los carcinomas epidermoides de cabeza y cuello (CECC), son un grupo poco frecuente de neoplasias, en los Estados Unidos representan el 3.2% de todos los cánceres1,2. Si bien su frecuencia global se encuentra en disminución, los tumores localizados en la orofaringe han aumentado de forma considerable2. El virus del papiloma humano (HPV) es responsable de este aumento. Se ha descripto que los tumores de orofaringe, asociados al HPV, ocurren en pacientes más jóvenes, con enfermedad de bajo volumen a nivel del tumor primario, pero elevada incidencia de metástasis ganglionares, con adenopatías quísticas2,3. La detección del virus del HPV, por inmunohistoquímica (IHQ) o por reacción en cadena de la polimerasa (PCR) son factores pronósticos importantes que siempre deben ser tenidos en cuenta para el tratamiento de estos tumores (AU)
Epidermoid carcinomas of the head and neck are a rare group of tumors, in the United States they account for 3.2% of all cancers. Although their overall frequency is decreasing, tumors located in the oropharynx have increased considerably. Human papillomavirus (HPV) is responsible for this increase. It has been described that oropharyngeal tumors, associated with HPV, occur in younger patients, with low volume disease at the primary tumor level but a high incidence of lymph node metastases, with cystic lymphadenopathy. Detection of HPV virus by immunohistochemistry (IHC) or polymerase chain reaction (PCR) are important prognostic factors that should always be taken into account for the treatment of these tumors (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas/diagnóstico , Papillomaviridae , Prontuários Médicos , Estudos Retrospectivos , Uso de TabacoRESUMO
O objetivo do presente estudo foi identificar o perfil dos pacientes com câncer de boca e orofaringe referidos ao Ambulatório de Cirurgia de Cabeça e Pescoço de um hospital público em Belo Horizonte, através da revisão de prontuários dos pacientes atendidos no período de 2005 a 2015. As variáveis estudadas foram: idade, sexo, cor de pele, escolaridade, estado civil, endereço de residência, tabagismo, etilismo, localização do tumor, estadiamento clínico, diagnóstico histológico, tipo de tratamento efetuado, data de ingresso, data de realização da cirurgia e data da última consulta. A análise dos dados envolveu estatística descritiva, comparação das variáveis sociodemográficas e clínicas para o tipo de tratamento e os dois tipos de câncer por meio do teste de chi-quadrado. Adicionalmente foi realizada a análise espacial da distribuição dos casos de câncer de boca e orofaringe. Foram analisados 289 prontuários, a maioria dos pacientes eram do sexo masculino (227), brancos (117), casados (125), com média de idade de 58,6 anos. Quarenta e seis (15,9%) pacientes eram analfabetos e 147 (50,9%) primeiro grau incompleto; 72,7% dos pacientes moravam na região metropolitana de Belo Horizonte. O etilismo e tabagismo estavam presentes em 82,0% e 85,1% dos pacientes respectivamente. As localizações anatômicas mais acometidas foram base da língua, palato mole, assoalho da boca, pilar amigdalino, e borda lateral da língua. O diagnóstico de carcinoma de células escamosas foi reportado em 89,6% dos prontuários. Foi constatado o câncer em grau III e IV (avançado) em 196 (67,8%) pacientes. A média do tempo gasto desde o laudo da biópsia até a consulta no serviço de cabeça e pescoço do HC/UFMG foi 1,5 meses (1,7 DP); e entre a primeira consulta e a data da cirurgia foi 2,9 meses (4,4 DP). Segundo o tipo de câncer, 146 (50,5%) pacientes tinham câncer de boca e 143 (49,5%) câncer de orofaringe, e as comparações revelaram que os pacientes com câncer de orofaringe em comparação com os de boca foram preferivelmente: tabagistas, etilistas, diagnosticados em estádio avançado da doença, com 3 ou mais sítios afetados, receberam tratamento não cirúrgico e residiam a mais de 50km do centro hospitalar. Quanto ao tipo de tratamento efetuado 32,9% somente foram diagnosticados e não continuaram com o tratamento proposto. Quando se compara o tipo de tratamento recebido, as únicas variáveis associadas com a adesão ao tratamento foram o estadiamento clínico inicial (I/II) e ser casado. Na análise espacial foi encontrado que os bairros com maior número de casos estavam localizados principalmente nas regionais Nordeste, Noroeste e Venda Nova. Em relação às variáveis socioeconômicas (baixa renda e moradia em condição semiadequada), foi observado que a maioria dos casos ocorreram em bairros em que estas condições eram piores. Concluindo, o perfil sociodemográfico dos pacientes com câncer de boca não se difere daqueles com câncer de orofaringe atendidos no HC/UFMG
The aim of this study to identify the profiles of patients with oral and oropharyngeal cancer referred to the Departament of Head and Neck Surgery in a public hospital in Belo Horizontem, from 2005 to 2015. Medical records from the hospital were reviewed and the variables studied were age, gender, skin color, years of education, marital status, self-reported home address, smoking status, alcohol consumption, histopathologic diagnostic, the primary tumor location, the type of treatment, tumor staging, and dates of first, last consult and surgery...