Occupational Risk Factors for Laryngeal Cancer in Tunisia: A Case Control Study.

BACKGROUND: Tobacco use and alcohol consumption are the primary risk factors for laryngeal cancer (LC). In most populations, occupational exposures are likely to play a minor role in laryngeal carcinogenesis. We aimed to investigate the association between occupational exposure and laryngeal cancer. METHODS: It is a case-control study that included 140 cases diagnosed between January 2013 and December 2016 and 140 controls matched by sex, age, alcohol consumption, and tobacco consumption. RESULTS: Significantly increased risks were found amongst workers of the building sector (OR=4.621; 95% CI [1.826-11.693]) and the mechanical industry sector (OR=5.074; 95% CI [1.425-18.072]). Significant association of laryngeal cancer with various carcinogens was observed such as asbestos (p=0.009; OR=3.68; 95% CI [1.29-10.46]), paint vapors (p=0.005; OR=3.35; 95% CI [1.37-8.16]), solvents (p=0.001; OR=3.29: 95% CI [1.61-6.68]) and cement dust (p=0.003; OR=3.19: 95% CI [1.43-7.12]). After binary logistic regression, cement dust was independently correlated with LC (p=0.042; OR=3.93; 95% CI [1.04-14.78]. The administration sector was associated with decreased risk (p=0.001; OR=0.07; 95% CI [0.03-0.15]) as well as the health sector (p=0.001; OR=0.098; 95% CI [0.02-0.43]). CONCLUSIONS: Our results supported the role of occupational factors in developing LC. Further studies enabling an in-depth analysis of occupational exposures are necessary to provide a clearer definition of the etiological associations between single agents and circumstances of exposure and the genesis of LC.

Benralizumab as an Adjuvant Therapy for Recurrent Laryngeal Papillomatosis.

Recurrent respiratory (RRP) or laryngeal papillomatosis is the result of human papillomavirus-mediated benign tumor growth on the larynx and is challenging to manage. Benralizumab is a monoclonal antibody targeted against the alpha subunit of the IL-5 receptor on eosinophils. A 61-year-old male patient presented with refractory RRP following multiple surgical excisions. His disease course improved substantially when benralizumab was added to his asthma regimen. There is no clear mechanistic role suggested for benralizumab directly treating RRP. This case may represent a novel application of benralizumab as an adjuvant treatment for patients with RRP and comorbid asthma. Laryngoscope, 133:863-865, 2023.

Mouthwash Use and the Risk of Oral, Pharyngeal, and Laryngeal Cancer. A Meta-Analysis.

OBJECTIVE: The main aim of this study was to test whether the use of mouthwash is associated with subtypes of squamous cell carcinoma of the head and neck (SCCHN) and to test the potential risk of SCCHN depending on the mouthwash use duration, frequency, or alcoholic content. MATERIALS AND METHODS: We performed a meta-analysis using Web of Science and Scopus databases to detect the risk change associated with mouthwash use depending on the alcohol content, duration and frequency of use, and anatomical location. We used a random-effects model with the Sidik-Jonkman estimator for effect size model measures. RESULTS: We included 17 studies in the meta-analysis containing 17,085 cases and 20,032 controls. The risk difference for SCCHN between mouthwash users and non-users was minimal, with a value of -0.02 [-0.05, 0.01]. Alcoholic mouthwash use was associated with a minimal decrease in risk (of -0.01 [-0.07, 0.05]). Frequent usage of mouthwash was associated with a statistically significant risk increase for SCCHN but the risk increase was marginal (0.04, [0.01, 0.06]). CONCLUSIONS: Overall, our study failed to show a statistically significant correlation between mouthwash use and the risk of SCCHN. The only statistically significant correlation that we could identify was between frequent usage and SCCHN, potentially caused by prolonged contact between some constituents of mouthwash (possibly alcohol) and the oral epithelium.

Micronucleus Formation in Primary Oropharyngeal Epithelial Cells Reveals Mutagenicity of Cement Dusts.

BACKGROUND/AIM: Epidemiological studies showed an increased risk of developing laryngeal head and neck squamous cell carcinoma (HNSCC) for employees working in the construction business. This suggested a causal link between exposure to cement particles and development of HNSCC but data were missing. MATERIALS AND METHODS: We established an Organisation for Economic Co-operation and Development (OECD) guideline 487-conform micronucleus assay (MNA) using oropharyngeal mucosa-derived primary epithelial cells (OPCs) ex vivo. OPCs from healthy mucosa of 52 donors were cultured in vitro and incubated with serial concentrations of two common cement particles. Mitomycin C was used as a soluble positive control, and TiO2 and DQ12 were used as negative and positive particle controls. Bi-nucleated cells were counted and the mitotic index (MI) was determined. Subsequently, micronuclei-containing bi-nucleated cells (MN+) were counted. RESULTS: Cement particles, in concentrations not significantly reducing ex vivo proliferation according to mitotic index, dose-dependently increased micronuclei formation. CONCLUSION: Through the establishment of an OECD guideline 487 conform MNA, we demonstrate the mutagenic effects of cement on human OPCs.

RNA Sequencing Reveals Cancer-Associated Changes in Laryngeal Cells Exposed to Non-Acid Pepsin.

OBJECTIVE: Laryngopharyngeal reflux (LPR) is a common affliction that contributes to laryngeal inflammation, symptoms that impact quality of life, and life-threatening illnesses such as cancer. Effective treatment strategies for LPR are lacking. Pepsin is a proinflammatory and carcinogenic element of refluxate. Investigation of molecular pathways involved in pepsin-mediated damage may lead to identification of novel biomarkers and therapeutic targets for LPR. In this study, RNA sequencing was used to examine changes in human laryngeal epithelial cells following brief pepsin insult. Cells were immortalized to generate a model to aid future study of laryngeal injury and therapeutics. STUDY DESIGN: In vitro translational. METHODS: Laryngeal epithelial cells were cultured from a patient without signs or symptoms of LPR or laryngeal cancer. Cells were treated with 0.1 mg/ml pepsin for 1 hour or normal growth media (control) prior to RNA sequencing. Cells were immortalized via HPV E6/7 and characterized by microscopy, immunohistochemistry, G-banding, and soft agar assay. RESULTS: Three hundred ninety-seven genes exhibited differences in expression with pepsin treatment (P < .05). Pathway analysis revealed association with cancer and related signaling processes including dysregulation of cancer-associated molecules, Metastasis-Associated Lung Adenocarcinoma Transcript 1 and KRT82, and the long-noncoding RNA, lipoprotein receptor-related protein 1 (LRP1)-AS, which regulates the putative pepsin receptor LRP1. CONCLUSIONS: A single, brief exposure to pepsin activated cancer-associated signaling pathways in laryngeal cells in vitro, revealing novel mechanisms by which chronic reflux may contribute to carcinogenesis. The cell line developed herein represents a novel tool in which to investigate pepsin-dysregulated pathways identified by RNA sequencing and disparities of tumor proneness of laryngeal subsites. LEVEL OF EVIDENCE: N/A Laryngoscope, 131:121-129, 2021.

Association between ambient air pollution and laryngeal neoplasms incidence in twelve major Chinese cities, 2006-2013.

Epidemiological evidence has suggested that ambient air pollution is an increasingly important risk factor for respiratory diseases without assessing its influence on laryngeal neoplasms incidence in China. We constructed two-way fixed effect models and Poisson regression models to explore the effects of ambient air pollutants including nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter less than or equal to 10 µm in aerodynamic diameter (PM10) on incidence of laryngeal neoplasms in twelve major cities in China over the period 2006-2013. The annual average concentration for PM10, SO2, and NO2 was 107.22 µg/m3, 44.07 µg/m3, and 46.71 µg/m3 with standard deviations of 24.84 µg/m3, 13.68 µg/m3, and 9.19 µg/m3, respectively. We observed that ambient air pollutants were significantly positively correlated with the incidence of laryngeal neoplasms, especially for NO2. The relative risks of overall incidence of laryngeal neoplasms in the current period were 1.20, 1.04, and 1.00 for NO2, SO2, and PM10, with 95% confidence intervals (CIs) of 1.01-1.43, 0.93-1.16, and 0.96-1.05, respectively. Moreover, this deleterious impact was stronger in the male than in the female, likely due to genetic predisposition caused by longer exposure to more serious air pollution for men. Our findings complement the epidemiological evidence of laryngeal neoplasms due to ambient air pollution and reinforce the necessity of policy efforts to control the noxious air pollution emissions.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

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.

Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts.

Age at Exposure to Arsenic in Water and Mortality 30-40 Years After Exposure Cessation.

Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30-40 years after a distinct period of very high water arsenic concentrations (1958-1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001-2010 by sex and age at potential first exposure. A remarkable relationship with age at first exposure was found for bronchiectasis, with increased risk in adults 30-40 years after exposure being confined to those who were in utero (SMR = 11.7, 95% confidence interval (CI): 4.3, 25.4) or aged 1-10 years (SMR = 5.4, 95% CI: 1.1, 15.8) during the high-exposure period. Increased SMRs for lung, bladder, and laryngeal cancer were evident for exposures starting at all ages, but the highest SMRs were for exposures beginning at birth (for bladder cancer, SMR = 16.0 (95% CI: 10.3, 23.8); for laryngeal cancer, SMR = 6.8 (95% CI: 2.2, 15.8); for lung cancer, SMR = 3.8 (95% CI: 2.9, 4.9)). These findings suggest that interventions targeting early-life arsenic exposure could have major impacts in reducing long-term mortality due to arsenic 30-40 years after exposure ends.

Modeling Variables With a Spike at Zero: Examples and Practical Recommendations.

In most epidemiologic studies and in clinical research generally, there are variables with a spike at zero, namely variables for which a proportion of individuals have zero exposure (e.g., never smokers) and among those exposed the variable has a continuous distribution. Different options exist for modeling such variables, such as categorization where the nonexposed form the reference group, or ignoring the spike by including the variable in the regression model with or without some transformation or modeling procedures. It has been shown that such situations can be analyzed by adding a binary indicator (exposed/nonexposed) to the regression model, and a method based on fractional polynomials with which to estimate a suitable functional form for the positive portion of the spike-at-zero variable distribution has been developed. In this paper, we compare different approaches using data from 3 case-control studies carried out in Germany: the Mammary Carcinoma Risk Factor Investigation (MARIE), a breast cancer study conducted in 2002-2005 (Flesch-Janys et al., Int J Cancer. 2008;123(4):933-941); the Rhein-Neckar Larynx Study, a study of laryngeal cancer conducted in 1998-2000 (Dietz et al., Int J Cancer. 2004;108(6):907-911); and a lung cancer study conducted in 1988-1993 (Jöckel et al., Int J Epidemiol. 1998;27(4):549-560). Strengths and limitations of different procedures are demonstrated, and some recommendations for practical use are given.

Asbestos exposure and laryngeal cancer mortality.

OBJECTIVES/HYPOTHESIS: Occupational exposure to asbestos occurs in many workplaces and is well known to cause asbestosis, lung cancer, and mesothelioma. However, the link between asbestos exposure and other malignancies was not confirmed. The aim of the current meta-analysis was to provide a summary measure of risk for laryngeal cancer associated with occupational asbestos exposure. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases were searched for studies characterizing the association between asbestos and laryngeal cancer. Standardized mortality rate (SMR) with its 95% confidence interval (CI) of each study was combined using a fixed or random effect model. RESULTS: Significantly increased SMR for laryngeal cancer was observed when subjects were exposed to asbestos (SMR = 1.69, 95% CI = 1.45-1.97, P < .001), with little evidence of heterogeneity among studies (Q = 15.39, P = .803, I(2) = 0.0%). Effect estimates were larger for cohorts controlling for male subjects, Europe and Oceania, mining and textile industries, exposure to crocidolite, long study follow-up (>25 years), and SMR for lung cancer > 2.0. Publication bias was not detect by Begg test (P = .910) and Egger test (P = .340). CONCLUSIONS: Our study supports the association of exposure to asbestos with an increased risk of laryngeal cancer mortality among male workers. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1169-1174, 2016.

Association between MDM2 rs769412 and rs937283 polymorphisms with alcohol drinking and laryngeal carcinoma risk.

TARGET: To investigate the association between the interactions of murine double minute 2 (MDM2) polymorphisms (rs769412 and rs937283) with alcohol drinking and laryngeal carcinoma. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes status of MDM2 rs769412 and rs937283 polymorphisms among 126 cases and 120 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the chi-squared test, which was adopted to analyze the association between MDM2 rs769412 and rs937283 polymorphisms and the susceptibility to larynx carcinoma in the drinking population. RESULTS: Genotypes distributions of MDM2 rs769412 and rs937283 polymorphisms in the control group were in accordance with Hardy-Weinberg equilibrium (HWE). MDM2 rs769412 GG genotype and G allele significantly increased laryngeal carcinoma risk (GG vs. AA: OR=3.17, 95% CI=1.25-8.04; G vs. A: OR=1.88, 95% CI=1.24-2.84). Furthermore, the mutant genotypes of MDM2 rs937283and rs769412 were remarkablely associated with the increased risk for laryngeal carcinoma in drinking population (rs937283: OR=2.67, 95% CI=1.40-5.07; rs769412: OR=3.76, 95% CI=1.62-8.75). CONCLUSION: MDM2 polymorphisms are correlated with the onset of laryngeal carcinoma. The relationship is strengthened by alcohol drinking.

Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants.

BACKGROUND: The effect of artificial sweetener consumption on cancer risk has been debated in animal models for over four decades. To further investigate this relationship, this study aims to synthesise results from several of the most recent studies in humans. METHODS: An online literature search was performed in MEDLINE from 2003 to 2014 using Ovid, PubMed, Web of Science, and Scopus using keywords 'artificial', 'sweetener' and 'cancer'. Ninety-two results were then manually assessed for eligibility. Studies were included if the relationship between artificial sweeteners and cancer was their central hypothesis, and if they adjusted for age, gender, smoking status and body mass index. Extracted data included study design, patient characteristics, outcome measure and results. RESULTS: In the five publications that satisfied the inclusion criteria, significant direct associations with artificial consumption were found for laryngeal (odds ratio, OR 2.34, 95% CI: 1.20-4.55), urinary tract tumours (OR 2.12, 95% CI: 1.22-3.89), non-Hodgkin lymphoma in men (RR 1.31, 95% CI: 1.01-1.72), multiple myeloma in men (RR 2.02, 95% CI: 1.20-3.40) and leukaemia (RR 1.42, 95% CI: 1.00-2.02). Inverse relationships were found in breast (OR 0.70, 95% CI: 0.54-0.91, p trend = 0.015) and ovarian (OR 0.56, 95% CI: 0.38-0.81, p trend < 0.001) cancers. CONCLUSION: The statistical value of this review is limited by the heterogeneity and observational designs of the included studies. Although there is limited evidence to suggest that heavy consumption may increase the risk of certain cancers, overall the data presented are inconclusive as to any relationship between artificial sweeteners and cancer.

Cannabis smoke can be a major risk factor for early-age laryngeal cancer--a molecular signaling-based approach.

Epidermal growth factor receptor (EGFR) and its downstream elements are overexpressed in most cases of the head and neck squamous cell carcinoma. This study investigated the expression pattern of key proteins linked to the EGFR pathway in laryngeal carcinoma patients with a history of cannabis smoking. We selected 83 male glottic cancer patients, aged between 45 to 75 years with three distinct populations-nonsmoker, cigarette smoker, and cannabis smoker. Immunohistochemical staining was performed for EGFR, protein kinase B (PKB or Akt), nuclear factor kappa B p50 (NF-КB), and cyclooxygenase-2 (COX-2) followed by boolean scoring for statistical analysis. Experimental data showed upregulation of the selected EGFR cascade in tumor cells, stromal expression of EGFR, and nuclear localization of COX-2 in metaplastic gland cells of laryngeal cancer tissue sample. Statistical analyses indicated that overexpression of the EGFR cascade is significantly correlated to cannabis smoking. Cannabis smokers had higher expression (p < 0.01) of these onco-proteins with respect to both nonsmokers as well as cigarette smokers. Risk factor analysis showed high risk of these proteins expression in age <60 years (odds ratio (OR) > 1.5) as the lower age group had relatively higher number of cannabis smokers. This study provides evidence for a direct association between cannabis smoking and increased risk of laryngeal cancer. Higher expression of the EGFR cascade in cannabis smokers revealed that cannabis smoking may be a major cause for the early onset of aggressive laryngeal cancer.

Occupational polycyclic aromatic hydrocarbon exposure and risk of larynx cancer: a systematic review and meta-analysis.

Polycyclic aromatic hydrocarbons (PAH) are genotoxic substances formed during combustion. Occupational PAH exposure has been shown to increase the risk of lung cancer and may be associated with other respiratory cancers. We conducted a systematic review and meta-analysis to clarify the relationship between occupational PAH exposures and larynx malignancies. We searched EMBASE and MEDLINE (until July 2014) using a series of search strings developed to seek case-control studies or longitudinal studies of workers (Population) exposed to PAHs (Exposure) and their risk for larynx cancer incidence and/or mortality (Outcome). Two independent reviewers screened the titles and abstracts for eligible articles and a third reviewer negotiated consensus. Further assessments of eligibility and sources of bias were conducted in a similar manner. The study results were pooled with random effects meta-analysis. The search resulted in 3377 records. The data of 92 full-text articles representing 63 studies were included and extracted. The majority of studies (n=47) was judged likely to be biased; only 16 studies were judged as methodologically adequate. The pooled effect size was 1.45 (95% CI 1.30 to 1.62; I(2)=30.7%; [Formula: see text]=0.03) for larynx cancer incidence and 1.34 (95% CI 1.18 to 1.53; I(2)=23.8%; [Formula: see text]=0.03) for larynx cancer mortality. While few studies allowed an investigation of dose-response, these indicate a positive dose-response effect. Although most studies may underestimate the true effect due to inexact approximations of PAH exposure, the meta-analysis suggests a robust positive association between PAH and larynx cancer.

Laryngeal dysplasia: a long-term follow-up study.

PURPOSE: To assess the progression of precancerous laryngeal lesions to squamous cell carcinoma (SCC), defined by specific histopathological criteria, in patients with longterm follow-up. METHODS: Patients with laryngeal dysplasia, followed/ treated between 1985 and 2008, were retrospectively evaluated and classified according to the World Health Organization classification system (WHO). The investigated outcome parameters were progression of dysplasia to SCC, time interval to malignant transformation and continuation of smoking as potential risk factors. RESULTS: Fifty-nine patients were studied. Progression of dysplasia to SCC between the first and the final histological examination was statistically significant (p<0.0001). Malignant transformation appeared in 29 patients (49.2%). Serious dysplasia was more likely to progress to SCC (64.8%) compared to mild (41.7%) or moderate (44.4%) (p<0.0001). However, the time interval needed in these 29 cases to progress to cancer was not statistically related to the initial histological diagnosis. Continuation of smoking did not affect the progression of disease. However, the mean time from dysplasia to laryngeal cancer was much longer in patients who quitted smoking (33.5 months) vs those who continued smoking (19.5 months), with a marginal statistical difference (p=0.057). CONCLUSION: All patients with laryngeal dysplasia should be followed up at regular intervals. The progression of dysplasia to SCC did not seem to be directly related to the continuation of smoking or not. However, large long-term follow- up studies taking into account the degree of exposure (e.g. time of exposure, number of cigarettes) are needed in order to clarify risk factors and proper management. Consensus guidelines in diagnosis, follow-up, and treatment would improve substantially the current clinical practice.

Inhaled corticosteroid use and risks of lung cancer and laryngeal cancer.

BACKGROUND: Chronic inflammation has been implicated in the pathogenesis of several cancers, including lung and laryngeal cancer. The objective of the study is to elucidate the association between ICS use and diagnosis of lung and laryngeal cancer. METHODS: A nested case-control study based on the Korean national claims database included new adult users of inhaled medications between January 1, 2007, and December 31, 2010. Patients diagnosed with lung cancer or laryngeal cancer after enrollment were identified as cases and up to five control individuals matched for age, sex, diagnosis of asthma or COPD, Charlson Comorbidity Index scores, number of health care visits, and initiation date were selected. RESULTS: From the 792,687 eligible cohort, 9177 individuals diagnosed with lung cancer were matched with 37,048 controls. Additionally, 408 laryngeal cancer patients and 1651 controls were matched. ICS use was associated with a decreased rate of lung cancer diagnosis [adjusted odds ratio (aOR), 0.79; 95% confidence interval (CI), 0.69-0.90]. The inverse association between ICS use and lung cancer risk was dose dependent (P < 0.0001 for the trend). However, no reduction in the risk of laryngeal cancer among ICS users was identified (aOR, 1.06; 95% CI, 0.62-1.18). CONCLUSION: The use of ICS is associated with a reduced risk of lung cancer but not of laryngeal cancer.

Mouthwash and oral cancer risk quantitative meta-analysis of epidemiologic studies.

BACKGROUND: Use of mouthwash and an increased risk of oral cancer has been a source of controversy for decades. A meta-analysis of epidemiological studies of mouthwash and oral cancer and, specifically, mouthwash containing >25% alcohol, was undertaken. METHODS: Summary estimates were obtained with maximum likelihood estimates from random effects models. Sensitivity analyses were conducted to evaluate the influence of various inclusion. RESULTS: Eighteen studies were included in the meta-analysis. There was no statistically significant associations found between regular use of mouthwash and risk of oral cancer (RR=1.13; 95% CI (0.95-1.35)). There was no significant trend in risk of oral cancer associated with increased daily usage of mouthwash (p=0.11). There was no association between reported use of mouthwash specifically containing alcohol and risk of oral cancer (RR=1.16; 95% CI (0.44, 3.08)). CONCLUSIONS: This quantitative analysis of mouthwash use and oral malignancy revealed no statistically significant associations between mouthwash use and risk of oral cancer, nor any significant trend in risk with increasing daily use; and no association between use of mouthwash containing alcohol and oral cancer risk.