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1.
Int J Cancer ; 154(2): 389-402, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37694289

RESUMO

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Papillomavirus Humano 16 , Papillomavirus Humano , Neoplasias de Cabeça e Pescoço/diagnóstico
2.
Int J Cancer ; 152(10): 2069-2080, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36694401

RESUMO

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Papillomavirus Humano , Marcadores Genéticos , Fatores de Risco , Papillomavirus Humano 16/genética , Anticorpos Antivirais , Fatores de Transcrição/genética , Proteínas Oncogênicas Virais/genética
3.
Br J Cancer ; 123(9): 1456-1463, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32830199

RESUMO

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/etiologia , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/etiologia , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar/patologia , Fatores de Tempo , Adulto Jovem
4.
Epidemiology ; 31(1): 145-154, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577634

RESUMO

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.


Assuntos
Carcinógenos , Neoplasias Laríngeas , Doenças Profissionais , Exposição Ocupacional , Amianto/toxicidade , Carcinógenos/toxicidade , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Laríngeas/induzido quimicamente , Neoplasias Laríngeas/epidemiologia , Masculino , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Fatores de Risco , Dióxido de Silício/toxicidade
5.
Int J Cancer ; 143(1): 32-44, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29405297

RESUMO

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.


Assuntos
Neoplasias Hipofaríngeas/mortalidade , Neoplasias Laríngeas/mortalidade , Neoplasias Bucais/mortalidade , Fumar/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Europa (Continente)/epidemiologia , Feminino , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Análise de Regressão , Fumar/efeitos adversos , Análise de Sobrevida
6.
Int J Cancer ; 136(5): 1125-39, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24996155

RESUMO

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Educação , Neoplasias de Cabeça e Pescoço/etiologia , Renda/estatística & dados numéricos , Fumar/efeitos adversos , Estudos de Casos e Controles , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fatores Socioeconômicos
7.
J Ir Dent Assoc ; 61(3): 141-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26285566

RESUMO

UNLABELLED: The current Ebola outbreak in West Africa is a global health emergency with implications for all healthcare professionals. This article will review the clinical features, transmission and oral manifestations of Ebola virus infection, and discuss the implications of the current outbreak for dental practices in Ireland. Guidance for managing suspected cases and contacts is also provided. CONCLUSIONS: Although Ebola is an alarming disease with a very high mortality rate, it is extremely unlikely that the dental team will encounter a new presentation of Ebola or that it will pose a significant transmission risk. The dental team should be aware of the Health Protection Surveillance Centre (HPSC) Algorithm for Ebola Virus Disease Risk Assessment, and it should be followed as necessary. It is advised to defer dental treatment for 21 days after possible exposure to the Ebola virus.


Assuntos
Assistência Odontológica , Doença pelo Vírus Ebola/diagnóstico , África Subsaariana , Infecções Assintomáticas , Surtos de Doenças , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/transmissão , Humanos , Irlanda , Doenças da Boca/virologia
8.
PLoS Genet ; 7(3): e1001333, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21437268

RESUMO

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻8); rs1229984-ADH1B, p = 7 × 10⁻9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.


Assuntos
Estudo de Associação Genômica Ampla , Neoplasias de Cabeça e Pescoço/genética , Adulto , Idoso , Aldeído Desidrogenase/genética , Biomarcadores Tumorais/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Variação Genética , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Raciais , Fatores de Risco
9.
Br Dent J ; 237(7): 543-549, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39394298

RESUMO

Syphilis is an infectious disease which can present with multitudinous mucocutaneous manifestations. Often referred to as the 'great mimicker', syphilis can present with non-specific symptoms and has a tropism for various organ systems. The oral cavity has been identified as a site commonly affected in the early stages of syphilis infection. Identification of the diverse presentations seen across the different stages of syphilis infection can assist in early diagnosis and treatment for this cohort of patients. Despite accurate diagnostic tools and the susceptibility of the infection to standard antimicrobial therapy, syphilis infections continue to rise worldwide.We present the clinical features and management of six cases of oral syphilis who presented to our unit. One case presented in 2008, but the other five cases presented between 2016 and 2023, reflecting the increasing incidence of syphilis infection. Five cases presented in the secondary stage of the infection while one presented with a primary infection in the form of a single chancre.The documented cases demonstrate the non-specific and variable clinical features of oral syphilis and highlight the importance of awareness in the dental profession of these manifestations. Dentists have an important role to play in recognising the disease and arranging appropriate testing for early intervention. This will not only reduce the incidence of the devastating consequences of tertiary infections but will also result in reduced spread of the disease.


Assuntos
Doenças da Boca , Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Masculino , Adulto , Doenças da Boca/diagnóstico , Doenças da Boca/microbiologia , Pessoa de Meia-Idade , Feminino , Diagnóstico Diferencial , Antibacterianos/uso terapêutico , Cancro/diagnóstico
10.
Br Dent J ; 236(4): 317-321, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38388611

RESUMO

Biologic drugs are drugs made by living organisms and the term is usually limited to monoclonal antibodies or receptors targeting specific cytokines or cells that have been developed in recent decades. These drugs have had an enormous impact on the management of cancers, including head and neck cancers, and immune-mediated inflammatory conditions, for example, rheumatoid arthritis and inflammatory bowel disease. General dental practitioners will routinely be managing patients who are on these medications for a wide range of systemic conditions. These drugs also have a limited role in the management of immune-mediated oral mucosal disease. In this article, we will introduce the range of biological agents and their systemic indications and then elaborate on their use in oral mucosal disease and the disadvantages associated with their use.


Assuntos
Artrite Reumatoide , Produtos Biológicos , Humanos , Odontólogos , Papel Profissional , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Terapia Biológica
11.
Front Cell Infect Microbiol ; 14: 1417946, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39286811

RESUMO

Fusobacterium nucleatum is an anaerobic commensal of the oral cavity recently reported to be associated with cancers of the gastrointestinal tract and oral squamous cell carcinoma (OSCC). In this study, we investigate the impact on oral keratinocytes of infection with a genetically diverse set of strains of F. nucleatum subsp. polymorphum recovered from patients with oral dysplasia (n=6). We employed H357 oral keratinocytes derived from a stage 1 OSCC and H376 cells derived from a stage 3 OSCC. Adhesion phenotypes were strain specific, with 3/6 clinical isolates examined exhibiting higher adherence to the stage 3 H376 cell line. Conversely, intracellular invasion was greatest in the H357 cells and was associated with specific transcriptional responses including autophagy and keratinization. Infection of both H357 and H376 cell lines induced transcriptional and cytokine responses linked to cancer cell migration and angiogenesis. F. nucleatum infection induced greater levels of MMP9 secretion in the H376 cell line which was associated with enhanced motility and invasion phenotypes. Additionally, the degree of F. nucleatum induced invasive growth by H376 cells varied between different clinical isolates of F. nucleatum subsp. polymorphum. Blockage of CCL5 signalling using the inhibitor metCCL5 resulted in reduced keratinocyte invasion. F. nucleatum infection also induced expression of the pro-angiogenic chemokine MCP-1 and the angiogenic growth factor VEGF-A resulting in increased capillary-like tube formation in HUVEC cells, most significantly in H376 cells. Treatment of HUVEC cells with resveratrol, a VEGF-A signalling inhibitor, significantly attenuated F. nucleatum induced tube formation. Our data indicate that the outcomes of F. nucleatum-oral cell interactions can vary greatly depending on the bacterial genotype and the malignant phenotype of the host cell.


Assuntos
Infecções por Fusobacterium , Fusobacterium nucleatum , Queratinócitos , Neoplasias Bucais , Humanos , Fusobacterium nucleatum/patogenicidade , Queratinócitos/microbiologia , Neoplasias Bucais/microbiologia , Neoplasias Bucais/patologia , Infecções por Fusobacterium/microbiologia , Linhagem Celular Tumoral , Movimento Celular , Aderência Bacteriana , Carcinoma de Células Escamosas/microbiologia , Carcinoma de Células Escamosas/patologia , Neovascularização Patológica/microbiologia , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Citocinas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Boca/microbiologia
12.
Microb Genom ; 10(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38529905

RESUMO

Fusobacterium nucleatum is an anaerobic commensal of the oral cavity associated with periodontitis and extra-oral diseases, including colorectal cancer. Previous studies have shown an increased relative abundance of this bacterium associated with oral dysplasia or within oral tumours. Using direct culture, we found that 75 % of Fusobacterium species isolated from malignant or potentially malignant oral mucosa were F. nucleatum subsp. polymorphum. Whole genome sequencing and pangenome analysis with Panaroo was carried out on 76 F. nucleatum subsp. polymorphum genomes. F. nucleatum subsp. polymorphum was shown to possesses a relatively small core genome of 1604 genes in a pangenome of 7363 genes. Phylogenetic analysis based on the core genome shows the isolates can be separated into three main clades with no obvious genotypic associations with disease. Isolates recovered from healthy and diseased sites in the same patient are generally highly related. A large repertoire of adhesins belonging to the type V secretion system (TVSS) could be identified with major variation in repertoire and copy number between strains. Analysis of intergenic recombination using fastGEAR showed that adhesin complement is shaped by horizontal gene transfer and recombination. Recombination events at TVSS adhesin genes were not only common between lineages of subspecies polymorphum, but also between different subspecies of F. nucleatum. Strains of subspecies polymorphum with low copy numbers of TVSS adhesin encoding genes tended to have the weakest adhesion to oral keratinocytes. This study highlights the genetic heterogeneity of F. nucleatum subsp. polymorphum and provides a new framework for defining virulence in this organism.


Assuntos
Transferência Genética Horizontal , Mosaicismo , Humanos , Filogenia , Fusobacterium/genética , Fenótipo , Dosagem de Genes
13.
Head Neck ; 46(9): 2261-2273, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38850089

RESUMO

BACKGROUND: Head and neck cancer (HNC) incidence is on the rise, often diagnosed at late stage and associated with poor prognoses. Risk prediction tools have a potential role in prevention and early detection. METHODS: The IARC-ARCAGE European case-control study was used as the model development dataset. A clinical HNC risk prediction model using behavioral and demographic predictors was developed via multivariable logistic regression analyses. The model was then externally validated in the UK Biobank cohort. Model performance was tested using discrimination and calibration metrics. RESULTS: 1926 HNC cases and 2043 controls were used for the development of the model. The development dataset model including sociodemographic, smoking, and alcohol variables had moderate discrimination, with an area under curve (AUC) value of 0.75 (95% CI, 0.74-0.77); the calibration slope (0.75) and tests were suggestive of good calibration. 384 616 UK Biobank participants (with 1177 HNC cases) were available for external validation of the model. Upon external validation, the model had an AUC of 0.62 (95% CI, 0.61-0.64). CONCLUSION: We developed and externally validated a HNC risk prediction model using the ARCAGE and UK Biobank studies, respectively. This model had moderate performance in the development population and acceptable performance in the validation dataset. Demographics and risk behaviors are strong predictors of HNC, and this model may be a helpful tool in primary dental care settings to promote prevention and determine recall intervals for dental examination. Future addition of HPV serology or genetic factors could further enhance individual risk prediction.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Neoplasias de Cabeça e Pescoço/epidemiologia , Feminino , Pessoa de Meia-Idade , Medição de Risco , Estudos de Casos e Controles , Idoso , Adulto , Reino Unido/epidemiologia , Modelos Logísticos , Fatores de Risco , Europa (Continente)/epidemiologia
14.
Nat Commun ; 15(1): 7835, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244563

RESUMO

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.


Assuntos
Consumo de Bebidas Alcoólicas , Neoplasias de Cabeça e Pescoço , Análise da Randomização Mendeliana , Infecções por Papillomavirus , Fumar , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/epidemiologia , Fumar/efeitos adversos , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Masculino , Feminino , Fatores de Risco , Papillomaviridae/genética , Pessoa de Meia-Idade , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único
15.
Int J Cancer ; 133(11): 2688-95, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23719996

RESUMO

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables.


Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias Bucais/etiologia , Fumar/efeitos adversos , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Europa (Continente) , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/patologia , Fatores de Risco , Inquéritos e Questionários
16.
Front Oral Health ; 4: 1166037, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035251

RESUMO

The tongue and floor of the mouth are high-risk sites for oral squamous cell carcinoma (OSCC), while smoking is its most significant risk factor. Recently, questions have been raised as to the role of the oral microbiome in OSCC because of a wealth of evidence demonstrating that the microbiome of OSCC differs from that of healthy mucosa. However, oral site and smoking also have a significant impact on oral microbial communities, and to date, the role these factors play in influencing the dysbiotic microbial communities of OSCC and precursor lesions has not been considered. This review aims to examine the influence of site and smoking on the oral microbiome and, in turn, whether these microbiome changes could be involved in oral carcinogenesis.

17.
J Oral Microbiol ; 15(1): 2263971, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795170

RESUMO

We investigated bacterial colonisation patterns of healthy mucosa (buccal, tongue, palate and floor of mouth) in a cohort of adults in order to determine how smoking, tooth loss, plaque levels and oral hygiene practices impacted on mucosal colonisation. A total of 322 swabs were recovered from 256 participants, of whom 46% were current smokers. We analysed colonization by sequencing the V1-V3 regions of the 16S rRNA gene. Palate and tongue microbiomes generally exhibited greater biodiversity than buccal and floor of mouth. Although Neisseria, Lautropia and Haemophilus spp. showed reduced abundance in smokers, buccal mucosa specifically showed a significant increase in Prevotella spp., whereas tongue and floor of mouth tended towards increased abundance of Streptococcus spp. Unexpectedly, tooth brushing frequency had a greater impact on mucosal community structure than plaque levels. Tooth loss was associated with significant reductions in mucosal biodiversity and had site-specific impacts, with buccal communities showing increased abundance of periodontitis-associated species and Rothia mucilaginosa, whereas tongue communities exhibited increased abundance of several streptococcal OTUs and reduced abundance of Haemophilus spp. This study highlights the complex relationship between mucosal colonisation and host factors, highlighting the need for careful consideration of these factors in mucosal microbiome studies.

18.
Int J Cancer ; 130(10): 2397-406, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21671472

RESUMO

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry.


Assuntos
Neoplasias/epidemiologia , Ocupações , Adulto , Idoso , Estudos de Casos e Controles , Indústria da Construção , Neoplasias Esofágicas/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Neoplasias Laríngeas/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Faríngeas/epidemiologia , Risco , Fatores de Risco
19.
J Ir Dent Assoc ; 58(2): 101-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22611791

RESUMO

PURPOSE OF THE STUDY: To increase public awareness about mouth cancer, the Dublin Dental University Hospital (DDUH) hosted an awareness day and free mouth check-up in September 2010. The messages of information, self-examination and risk management, and the importance of early detection, were available to all attendees. The role of general dental and medical practitioners in examination of the mouth was stressed. MATERIAL AND METHODS: A questionnaire regarding knowledge about the causes of and risk factors for mouth cancer, and a clinical check-up, were completed. RESULTS: A total of 1,661 individuals (675 male, 986 female) were examined. The mean age was 59.6 years. Just over one-third (36.5%) of those examined required no action, and slightly less (30%) were advised to return to their general dental or medical practitioner (GDP/GMP). Some 21% were advised about self-examination of the mouth, and 8% about smoking cessation. Of the remainder, 52 people (3.5%) were sent for a second opinion. Of these, 30 individuals were referred for further investigation, including biopsy in 27 cases. Following biopsy, five individuals were diagnosed with carcinoma in situ or carcinoma. CONCLUSIONS: The diagnosis of five people with mouth cancers, who may not otherwise have been identified for early treatment, highlights the need for regular mouth examination. It is inappropriate that such an exercise would remain the preserve of the dental teaching hospitals, and it is vital that all dentists take on the responsibility for regular mouth checks for all of their patients. More should be done to encourage those identified as high risk to visit their dentist. There is a need for recognition of the additional resources required for the detection and timely management of such cancers.


Assuntos
Carcinoma in Situ/diagnóstico , Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Neoplasias Bucais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais Universitários , Humanos , Irlanda , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Neoplasias Bucais/prevenção & controle , Exame Físico/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Fatores de Risco , Autoexame , Abandono do Hábito de Fumar , Inquéritos e Questionários
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120437, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34627019

RESUMO

The potential of Raman microspectroscopy of exfoliated cells has been demonstrated for oral cancer diagnosis. In this study, brush biopsies were collected from the buccal mucosa/tongue of healthy donors (n = 31) and from oral mucosal dysplastic lesions (n = 31 patients). Raman spectra were acquired and subjected to partial least squares-discriminant analysis (PLS-DA). The patient samples could be differentiated from healthy donor samples with 96% sensitivity and 95% specificity. Furthermore, PLS-DA models were developed based on cytopathological and histopathological assessment. Low and high grade dysplasia could be discriminated with 64% sensitivity and 65% specificity based on cytopathological assessment, while 81% sensitivity and 86% specificity could be achieved when histopathological assessment was within six months of the brush biopsy sampling. Therefore, this explorative study has successfully demonstrated that Raman spectroscopy may have a role in monitoring patients with dysplasia and may reduce the need for multiple biopsies.


Assuntos
Neoplasias Bucais , Análise Espectral Raman , Análise Discriminante , Humanos , Análise dos Mínimos Quadrados , Neoplasias Bucais/diagnóstico , Projetos Piloto , Sensibilidade e Especificidade
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