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Keywords: air pollution; chronic disease; particulate matter EN air pollution chronic disease particulate matter 1200 1203 4 09/01/22 20220901 NES 220901 Sinonasal inverted papilloma (IP) is a benign tumor with a propensity for malignant transformation in 5% to 7% of cases.1 Although its pathogenesis remains uncertain, recent epidemiologic studies have implicated environmental and occupational exposures, such as organic solvents and welding fumes as potential contributors to IP.2-4 A meta-analysis has showed that occupational exposure would increase the risk of developing sinonasal cancer.5 Sham et al performed a case-control study on patients with IP and reported a higher incidence with outdoor occupations, such as construction.4 They concluded this higher incidence is likely due to outdoor air pollution, but this effect has not been directly studied. Air pollution, chronic disease, particulate matter Further research into the effects of air pollution, including particulate matter, ozone, and NO SB 2 sb , is warranted, especially in locations with a wider range of air pollution. [Extracted from the article]

Summary The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer continues to increase in contrast to other head and neck cancer sites. There is a growing role for upfront surgery to treat these cancers in the era of organ preservation treatment strategies. This is becoming especially important in younger, healthier patients with HPV-associated squamous cell carcinoma. Surgery for oropharyngeal cancer has evolved from large, open transcervical and transmandibular approaches to minimally-invasive transoral endoscopic techniques. Advances in transoral endoscopic surgery (TES) have led to renewed interest in upfront surgical treatment for oropharyngeal carcinoma. Transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) are two techniques that allow for complete oncologic resection through the mouth in select patients, with minimal cosmetic deformity and optimal speech and swallow function after completion of therapy. In this article we will review transoral approaches to oropharyngeal carcinoma: its oncologic and functional outcomes, and its role in the multi-disciplinary treatment of oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Methylation profiling of tumor suppressor gene (TSGs) promoters is quickly becoming a powerful diagnostic tool for the early detection, prognosis, and even prediction of clinical response to treatment. Few studies address this in salivary gland tumors (SGTs); hence the promoter methylation profile of various TSGs was quantitatively assessed in primary SGT tissue to determine if tumor-specific alterations could be detected. Methodology: DNA isolated from 78 tumor and 17 normal parotid gland specimens was assayed for promoter methylation status of 19 TSGs by fluorescence-based, quantitative methylation-specific PCR (qMSP). The data were utilized in a binary fashion as well as quantitatively (using a methylation quotient) allowing for better profiling and interpretation of results. Principal Findings: The average number of methylation events across the studied genes was highest in salivary duct carcinoma (SDC), with a methylation value of 9.6, compared to the normal 4.5 (p<0.0003). There was a variable frequency and individual methylation quotient detected, depending on the TSG and the tumor type. When comparing normal, benign, and malignant SGTs, there was a statistically significant trend for increasing methylation in APC, Mint 1, PGP9.5, RAR-β, and Timp3. Conclusions/Significance: Screening promoter methylation profiles in SGTs showed considerable heterogeneity. The methylation status of certain markers was surprisingly high in even normal salivary tissue, confirming the need for such controls. Several TSGs were found to be associated with malignant SGTs, especially SDC. Further study is needed to evaluate the potential use of these associations in the detection, prognosis, and therapeutic outcome of these rare tumors. [ABSTRACT FROM AUTHOR]

Introduction: Radiation-associated soft tissue sarcomas of the neck (RASN) constitute a rare and aggressive tumor type. Methods: A retrospective chart review at the authors' institution revealed 3 patients with RASN. A systematic review of the literature was also conducted using MEDLINE, Ovid, the Cochrane Library, and Embase. Results: Patients within the authors' institutional chart review presented from 6 to 26 years after neck radiation with neck masses. All patients underwent surgical resection with clear margins, and adjuvant radiation was offered when feasible. Patients had no evidence of disease at most recent follow-up. A total of 867 articles were screened for systematic review, revealing 9 articles detailing outcomes of RASN. Studies were small and heterogeneous, precluding pooled data. The importance of complete surgical extirpation was noted. Conclusions: Complete surgical resection appears to be the mainstay of therapy, but there are limited data on management and outcomes of patients with RASN. [ABSTRACT FROM AUTHOR]

Introduction: Extirpation of multiple head and neck paragangliomas carries challenge due to close anatomic relationships with critical neurovascular bundles. Objectives: This study aims to assess whether the application of 3-D models can assist with surgical planning and treatment of these paragangliomas, decrease surgically related morbidity and mortality. Methods: Fourteen patients undergoing surgical resection of multiple head and neck paragangliomas were enrolled in this study. A preoperative 3-D model was created based on radiologic data, and relevant critical anatomic relationships were preoperatively assessed and intraoperatively validated. Results: All 14 patients presented with multiple head and neck paragangliomas, including bilateral carotid body tumors (CBT, n = 9), concurrent CBT with glomus jugulare tumors (GJT, n = 4), and multiple vagal paragangliomas (n = 1). Ten patients underwent genomic analysis and all harbored succinate dehydrogenase complex subunit D (SDHD) mutations. Under guidance of the 3-D model, the internal carotid artery (ICA) was circumferentially encased by tumor on 5 of the operated sides, in 4 (80%) of which the tumor was successfully dissected out from the ICA, whereas ICA reconstruction was required on one side (20%). Following removal of CBT, anterior rerouting of the facial nerve was avoided in 3 (75%) of 4 patients during the extirpation of GJT with assistance of a 3-D model. Two patients developed permanent postoperative vocal cord paralysis. There was no vessel rupture or mortality in this study cohort. Conclusion: The 3-D model is beneficial for establishment of a preoperative strategy, as well as planning and guiding the intraoperative procedure for resection of multiple head and neck paragangliomas. [ABSTRACT FROM AUTHOR]

To evaluate the incidence of a subsequent primary thyroid malignancy in patients with an index head and neck squamous cell carcinoma (HNSCC), we analyzed the National Cancer Institute’s Surveillance, Epidemiology, and End Results database to identify a cohort of patients who had been diagnosed with a primary HNSCC from 1973 through 2004. The study population was made up of 60,323 patients of all ages, roughly three-quarters of whom were male. A total of 60 patients (0.1%) developed a subsequent thyroid malignancy—not a statistically significant finding. The overall standard incidence ratio (SIR) for a subsequent thyroid malignancy was 1.58 (p < 0.05). The highest SIRs were seen during in the first 5 years after diagnosis of the original primary (SIR: 3.05; p < 0.05), more specifically in 2 to 11 months after diagnosis (SIR: 7.11; p < 0.05). Further analyses demonstrated that SIRs were significantly higher in males (SIR: 1.71), in patients aged 60 through 79 years (SIR: 1.71), in whites (SIR: 1.55), in patients who had undergone external-beam radiotherapy for their index primary (SIR: 1.84), in those whose tumor was initially staged as regional (SIR: 1.96), and in patients whose index primary was in the oral cavity (SIR: 1.71) or larynx (SIR: 1.88) (p < 0.05 for all). We conclude that the incidence of a subsequent primary thyroid malignancy in patients with an HNSCC is highest during the first 5 years after diagnosis of the index primary, reflecting the benefit of continued surveillance. [ABSTRACT FROM AUTHOR]

Introduction: Resection of carotid body tumor (CBT) in patients of advanced ages has not been appreciated. Objectives: This study aims to assess the clinical characteristics and perioperative comorbidities for CBT resection in patients of advanced age and to validate the application of an "isolated island" technique for extirpation of CBT. Methods: Eight patients of advanced age (≥60 years) who underwent CBT resection were enrolled as the study group (SG). Another 29 patients of younger age (<45 years old) underwent CBT extirpation were assigned as the control group (CG). The perioperative issues were compared between these 2 groups. Results: The "isolated island" technique was successfully applied for resection of CBT in all 37 patients. The prevalence of Shamblin classification I, II, and III tumors in the SG was 12.5%, 62.5%, and 25%; whereas in the CG was 10.3%, 55.2%, and 34.5%, respectively. Bilateral CBT was observed in 7 patients of the CG and none in the SG. Vascular reconstruction was required for 1 (12.5%) patient in the SG, while it was required for 8 (27.6%) patients in the CG. Postoperative vocal cord palsy occurred in 37.5% of patients in SG, whereas the vocal cord palsy (34.5%) and dysphagia (6.9%) were commonly encountered in CG. In addition to postoperative length of stay (P =.004), no significant difference for operative time, intraoperative blood loss, or mortality were observed between these 2 groups (P >.05). Conclusion: Extirpation of CBT in patients of advanced age is rationale in appropriately selected patients. The "isolated island" technique is safe for CBT resection with seemingly low complication rates. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human papillomavirus (HPV) is responsible for a growing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) among men and White individuals. Whether similar trends apply to women, non‐Whites, and non‐oropharyngeal squamous cell carcinomas (non‐OPSCCs) is unknown. METHODS: This is a cross‐sectional analysis combining 2 multi‐institutional case series of incident head and neck squamous cell carcinoma (HNSCC) cases. Incident HNSCCs from 1995 to 2012 were enrolled retrospectively using banked tumor samples and medical record abstraction. Incident HNSCCs from 2013 to 2019 were enrolled prospectively. The prevalence of tumor HPV biomarkers was tested over 3 time periods (1995‐2003, 2004‐2012, and 2013‐2019). Centralized testing was done for p16 immunohistochemistry (p16) and oncogenic HPV in situ hybridization (ISH). RESULTS: A total of 1209 incident cases of HNSCC were included. Prevalence of p16‐ and ISH‐positive tumors increased significantly for oropharynx cancers over time. The majority were positive after 2013 for White patients (p16, 92%; P <.001; ISH 94%; P <.001), Black patients (p16, 72%; P =.021; ISH 67%; P =.011), and Hispanic patients (p16, 100%; P =.04; ISH 100%; P =.013). For women with OPSCC, the prevalence of p16‐ and ISH‐positive tumors increased significantly to 82% (P <.001) and 78% (P =.004), respectively. For non‐OPSCCs, there was increased p16 and ISH positivity overall with 24% p16 and 16% ISH positivity in the most recent time period (P <.001 for both). CONCLUSIONS: The majority of OPSCCs in US tertiary care centers are now p16 and ISH positive for all sex and race groups. In some populations in the United States, 91% of OPSCCs are now caused by HPV. Few non‐OPSCCs are p16 and ISH positive. This study evaluates the prevalence of p16 and in situ hybridization positivity in head and neck cancers over time. This study shows an increase in prevalence over time among women and non‐Whites, 2 groups that are understudied in the epidemiology of human papillomavirus. [ABSTRACT FROM AUTHOR]

AbstractFanconi anemia (FA) and dyskeratosis congenita (DC) are rare inherited syndromes that cause head and neck squamous cell cancer (HNSCC). Prior studies of inherited forms of cancer have been extremely important in elucidating tumor suppressor genes inactivated in sporadic tumors. Here, we studied whether sporadic tumors have epigenetic silencing of the genes causing the inherited forms of HNSCC. Using bisulfite sequencing, we investigated the incidence of promoter hypermethylation of the 17 Fanconi- and DC-associated genes in sporadic HNSCC. Genes that only showed methylation in the tumor patients were chosen for quantitative methylation-specific PCR (qMSP) in a set of 45 tumor and 16 normal patients. Three gene promoters showed differences in methylation: FancB (FAAP95, FA core complex), FancJ (BRIP1, DNA Helicase/ATPase), and DKC1 (dyskeratin). Bisulfite sequencing revealed that only FancB and DKC1 showed no methylation in normal patients, yet the presence of promoter hypermethylation in tumor patients. On qMSP, 1/16 (6.25) of the normal mucosal samples from non-cancer patients and 14/45 (31.1) of the tumor patients demonstrated hypermethylation of the FancB locus (p < 0.05). These results suggest that inactivation of FancB may play a role in the pathogenesis of sporadic HNSCC.Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Recursive partitioning analysis (RPA) from the Radiation Therapy Oncology Group (RTOG)‐0129 has identified a low‐risk group of patients with oropharynx cancer (OPC) who might benefit from therapeutic de‐intensification. These risk groups have not yet been reproduced in an independent cohort treated heterogeneously. Therefore, the objective of this analysis was to validate the RPA risk groups and examine the prognostic impact of novel factors. Methods: Patients with OPC were enrolled in a prospective study at 3 academic medical centers from 2013 to 2018. Medical record abstraction was used to ascertain clinical variables including staging and survival according to the 7th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. Human papillomavirus–positive tumor status was determined by p16 immunohistochemistry and/or HPV RNA in situ hybridization. Kaplan‐Meier and log‐rank methods were used to compare survival. Cox proportional hazards were used to generate univariate and multivariable hazard ratios (HRs). Results: Median follow‐up time was 3.2 years. The low‐, intermediate‐, and high‐risk groups had significant differences in 2‐year overall survival (OS, 99.1%; 95% CI, 94.4%‐99.9% vs OS, 93.0%; 95% CI, 74.7%‐98.2% vs OS, 80.0%; 95% CI, 40.9%‐94.6%; Poverall =.0001) and 2‐year progression‐free survival (PFS, 97.5%; 95% CI, 92.4%‐99.2% vs PFS, 89.3%; 95% CI, 70.3%‐96.4% vs PFS, 80.0%; 95% CI, 40.9%‐94.6%; Poverall <.002). After adjustment for age, sex, and level of educational attainment, OS and PFS were significantly lower for the intermediate‐ (OS adjusted hazard ratio [aHR], 5.0; 95% CI, 1.0‐23.0; PFS aHR, 3.4; 95% CI, 1.0‐11.5), and high‐ (OS aHR, 7.3; 95% CI, 1.4‐39; PFS aHR, 5.0; 95% CI, 1.2‐21.6) risk groups compared with the low‐risk group. Lower education was also independently significantly associated with worse OS (aHR, 8.9; 95% CI, 1.8‐44.3) and PFS (aHR, 3.1; 95% CI, 1.0‐9.6). Conclusions: In patients with OPC, the RTOG‐0129 RPA model is associated with OS and PFS in a heterogeneously treated cohort. In patients with oropharyngeal squamous cell carcinoma (OPC), the Radiation Therapy Oncology Group (RTOG)‐0129 recursive partitioning analysis model is associated with overall survival and progression‐free survival in a heterogeneously treated cohort. It is the hope that this study will contribute to identifying favorable, low‐risk patients with therapeutic implications for treatment de‐intensification in future clinical trials for OPC. [ABSTRACT FROM AUTHOR]

Background: Case‐control studies from the early 2000s demonstrated that human papillomavirus–related oropharyngeal cancer (HPV‐OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV‐OPC. Methods: HPV‐OPC patients and frequency‐matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi‐square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. Results: A total of 163 HPV‐OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV‐OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8‐6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1‐3.2]) and oral sex intensity (>5 sex‐years: aOR, 2.8 [95% CI, 1.1‐7.5]) remained associated with significantly increased odds of HPV‐OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1‐2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1‐2.4]) was associated with HPV‐OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122‐670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70‐378]) was associated with increased odds of HPV‐OPC. Conclusion: Number of oral sex partners remains a strong risk factor for HPV‐OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV‐OPC. This comprehensive behavioral case‐control study of human papillomavirus (HPV)‐related oropharyngeal cancer reveals that oral sex and number of partners remain strong risk factors for HPV‐related oropharyngeal cancer. Measures of oral sexual behavior—including early age and intensity of exposure—are independent risk factors, suggesting that these behaviors may explain additional nuances of how and why some individuals develop HPV‐related oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV-related tumors remain associated with an improved prognosis among older patients.Methods: In a retrospective study of OPSCCs diagnosed from 1995 to 2013 at 2 National Comprehensive Cancer Network-designated cancer centers, p16 immunohistochemistry and in situ hybridization (ISH) for HPV-16, high-risk DNA, and/or E6/E7 RNA were performed. The median age at diagnosis was compared by p16 and ISH tumor status. Trends in age were analyzed with nonparametric trends. Survival was analyzed with the Kaplan-Meier method and Cox proportional hazards models.Results: Among 239 patients, 144 (60%) were p16-positive. During 1998-2013, the median age increased among p16-positive patients (Ptrend = .01) but not among p16-negative patients (Ptrend = .71). The median age of p16-positive patients increased from 53 years (interquartile range [IQR] in 1995-2000, 45-65 years) to 58 years (IQR for 2001-2013, 53-64 years). Among patients ≥ 65 years old, the proportion of OPSCCs that were p16-positive increased from 41% during 1995-2000 to 75% during 2007-2013 (Ptrend = .04). Among all age groups, including older patients, a p16-positive tumor status conferred improved overall survival in comparison with a p16-negative status.Conclusions: The median age at diagnosis for HPV-related OPSCC is increasing as the proportion of OPSCCs caused by HPV rises among older adults. The favorable survival conferred by an HPV-positive tumor status persists in older adults. Cancer 2018;124:2993-9. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]