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Background: Aspirin intake might be inversely associated with head and neck cancer (HNC). Thus, we investigated this relationship within the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Methods: Four case–control studies within the INHANCE consortium were included (2024 cases, 4196 controls). Study‐specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression and subsequently pooled with DerSimonian‐Laird random‐effects model. Nonlinearity of the relationship between duration of intake and HNC was modeled with fractional polynomials. Results: Aspirin was inversely associated with HNC overall (OR = 0.48; 95% CI: 0.26, 0.91). Results for laryngeal cancer were similar (OR = 0.54; 95% CI: 0.30, 0.96). Analysis on duration of intake confirmed findings for HNC overall, showing also inverse associations for oropharyngeal and laryngeal cancer. Conclusions: This study suggests that aspirin intake may reduce the risk of HNC, driven mainly by decreases in risk for laryngeal and oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Objective: We analyzed the pooled case‐control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. Subjects and Methods: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. Results: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. Conclusion: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer. [ABSTRACT FROM AUTHOR]

There are controversial results about the role of "ex novo" HLA‐DR expression by tumor cells and its correlation with the oncological outcomes. Unfortunately, little is known about HLA‐DR expression in laryngeal cancer tumor cells. The main purpose of this retrospective study is to strengthen the usefulness of studying "ex novo" HLA‐DR expression on tumor cells from primary laryngeal squamous cell carcinoma (LSCC) patients and investigate its correlation with clinical outcome. We analyzed HLA‐DR expression by immunohistochemical analysis in 56 patients with LSCC. The "ex novo" HLA‐DR expression on laryngeal cancer tumor cells, assessing non‐neoplastic LSCC – adjacent tissue, and the association of HLA‐DR expression (HLA‐DR+) with clinical outcomes were investigated. HLA‐DR+ tumor cells were detected in 18/56 LSCC patients (32.1%). All specimens of non‐neoplastic laryngeal carcinoma‐adjacent tissue resulted HLA‐DR negative (HLA‐DR‐). A statistically significant association was observed between HLA‐DR + and well differentiated tumors (G1) (p<0.001). The Kaplan‐Meier method showed how HLA‐DR+ is significantly associated with both a better disease specific survival (HLA‐DR+=100% vs. HLA‐DR‐=77.4%; p=0.047) and a better relapse free survival (HLA‐DR+=100% vs. HLA‐DR‐=72.3%; p=0.021). Cox regression univariate analysis for death of disease confirmed a higher HR for HLA‐DR absence on the surface of epithelial tumor cell [HR:37.489; 95% CI:0.750‐18730.776; p=0.253] and for high‐grade (G3) tumors [HR:18.601; 95% CI:3.613‐95.764; p<0.0001]. Our results confirm that MHC class II HLA‐DR expression is activated in a sub‐set of LSCC patients. Evaluation of HLA‐DR expression in LSCC could be useful for prognosis and future approaches towards personalized therapy. [ABSTRACT FROM AUTHOR]

Objective: To summarize the latest evidence on head and neck cancer epidemiology from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Subjects and Methods: INHANCE was established in 2004 to elucidate the etiology of head and neck cancer through pooled analyses of individual‐level data on a large scale. We summarize results from recent INHANCE‐based publications updating our 2015 overview. Results: Seventeen papers were published between 2015 and May 2020. These studies further define the nature of risks associated with tobacco and alcohol, and occupational exposures on head and neck cancer. The beneficial effects on incidence of head and neck cancer were identified for good oral health, endogenous and exogenous hormonal factors, and selected aspects of diet related to fruit and vegetables. INHANCE has begun to develop risk prediction models and to pool follow‐up data on their studies, finding that ~30% of cases had cancer recurrence and 9% second primary cancers, with overall‐ and disease‐specific 5‐year‐survival of 51% and 57%, respectively. Conclusions: The number and importance of INHANCE scientific findings provides further evidence of the advantages of large‐scale internationally collaborative projects and will support the development of prevention strategies. [ABSTRACT FROM AUTHOR]

Due to lower female incidence, estimates of exogenous and endogenous hormonal factors in head and neck cancers (HNCs, comprising cancers of the oral cavity, oropharynx, hypopharynx, and larynx) among women have been inconsistent and unable to account for key HNC risk factors. We pooled data from 11 studies from Europe, North America, and Japan. Analysis included 1572 HNC female cases and 4343 controls. Pooled odds ratios (ORs) estimates and their 95% confidence intervals (CIs) were calculated using multivariate logistic regression models adjusting for tobacco smoking and alcohol drinking. Lower risk was observed in women who used hormone replacement therapy (HRT) (OR = 0.58; 95% CI: 0.34-0.77). Pregnancy (OR = 0.61; 95% CI: 0.42-0.90) and giving birth (OR = 0.59; 95% CI: 0.38-0.90) at <35 years of age were inversely associated with HNCs. An inverse association with HNC was observed with age at start of HRT use (OR = 0.59; 95% CI: 0.39-0.90) for each additional 10 years and with duration of use (OR = 0.87; 95% CI: 0.76-0.99 for every 3 years). Exogenous female hormone use is associated with a nearly twofold risk reduction in female HNCs. The lower female HNC incidence may, in part, be explained by endogenous and exogenous estrogen exposures. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16INK4a expression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC. While majority of OPSCC in the US (60%) were HPV16-positive, this proportion was 31% in Europe and only 4% in Brazil ( p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16-positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64-0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54-0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Sudden sensorineural hearing loss (SSNHL) is strictly related to inner ear vascular injuries and recently to some atherosclerotic risk factors. The pathogenic role of inflammatory molecules in atherosclerosis is well established. However, there is little knowledge about the potential role of inflammatory cytokines and adhesion molecules on SSNHL etiology. Study Design The aim of this study was to evaluate the role of proinflammatory genetic polymorphisms of the MCP-1 (CCL2), E-selectin, and interleukin (IL)−6 gene in SSNHL patients. Methods We evaluated the frequency and distribution of selected single nucleotide polymorphisms of the MCP-1 (CCL2), E-selectin, and IL-6 gene in 87 SSNHL patients and 107 healthy controls. Results Our results did not show significant difference between the compared groups for MCP-1 and E-selectin genes, whereas a significant difference was reported for the IL-6 gene ( P < .0001). Conclusions The main finding of our study is that the 174G/G polymorphism (with a wider distribution of wt/wt genotype in SSNHL patients than in the healthy controls) of the IL-6 gene is significantly associated with the risk of SSNHL, which is consistent with a previous finding on serum levels of IL-6 in SSNHL. It is possible that the variant acts as a triggering agent of different lipidemia-related phenotypes. Both the −174G/G polymorphism and elevated IL-6 levels in SSNHL patients could suggest that IL-6 plays a role in the inner ear involvement by atherosclerotic inflammatory events. Level of Evidence 3b Laryngoscope, 125:E28-E32, 2015 [ABSTRACT FROM AUTHOR]

Background Treatment for laryngeal squamous cell carcinoma (SCC) has been predominantly surgical for decades, but in the last 20 years nonsurgical modalities (radiotherapy), with the aim of organ preservation, also became predominant among advanced stages. Retrospectively evaluating our series of stage III and stage IV laryngeal SCCs, we compared the 2 main therapeutic modalities. Methods Medical records of 65 consecutive patients with advanced laryngeal SCC, from November 2005 to January 2009, were reviewed. Results Among irradiated patients 2-year organ preservation was 86% for cT2, 43% for cT3, and 17% for cT4a ( p = .037, Wilcoxon test). With respect to survival, the only significant differences between surgery and radiotherapy were detected among cT4a SCCs ( p = .03, Wilcoxon test), in favor of surgery. Conclusions The present results confirm the surgical recommendation for cT4a laryngeal SCCs. On the other hand, for T < 4, our results confirm that radiochemotherapy warrants a survival similar to that of total laryngectomy, thus allowing us to preserve the larynx in a relevant number of cases. © 2011 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Sudden hearing loss (HL) can be caused by autoimmune disorders localized to the inner ear or secondary to systemic immune diseases. Studies in autoimmune animal strains showing HL have reported changes in the cochlear stria vascularis. The authors investigated the presence of antiendothelial cell antibodies (AECA) to see if immunemediated vasculitis may play a role in human sudden HL. Study Design: A prospective study in patients with sudden HL. Methods: Fifteen consecutive patients (mean age, 32 y) affected by sudden HL and 14 normal subjects were included. Patients with familial deafness and metabolic diseases were excluded. Extensive audiovestibular, imaging, microbiological, immunological, and routine examinations were performed. AECA were detected on rat kidney tissue sections on the sera collected at −20°C. Results: AECA were positive in 8 of 15 patients (53%) (2 of 5 men and 6 of 10 women), thus differing significantly from the normal control population, in which only 2 of 14 tested AECA positive ( P = .023). Conclusions: In patients with sudden HL, immune-mediated vascular damage can have a pathogenetic role and AECA might represent a serological marker of vasculitis. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: The role of antiendothelial cell antibodies in systemic vasculitis has been reported. The aim of the study was to define the clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss., Study Design: A prospective study in patients with sudden sensorineural hearing loss., Methods: Serum samples were taken from 59 consecutive patients with sudden sensorineural hearing loss at time of presentation and from 28 normal control subjects. Indirect immunofluorescence assay was used to detect antiendothelial cell antibodies., Results: The prevalence of antiendothelial cell antibody detection was 54% (32 of 59 patients), with a statistically significant difference between patients and control subjects (P =.0004). Antiendothelial cell antibody positivity was significantly associated with absent recovery of hearing loss (P =.0020)., Conclusions: The cytotoxicity to endothelial cells of the inner ear by antiendothelial cell antibody-positive sera might play a role in causing the stria vascularis damage in immune-mediated sudden sensorineural deafness. The appearance of antiendothelial cell antibody is related to the poor outcome of hearing loss, and its detection could be helpful in the selection of particular patients with sensorineural hearing loss for specific immunosuppressive treatments.