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Purpose: This study aims to evaluate how various demographic factors impact the stage at diagnosis and, therefore, prognosis of laryngeal cancer., Materials and Methods: Using the National Cancer Database, 96,409 patients were diagnosed with laryngeal squamous cell carcinoma between 2004 and 2020. Early (stage 0 or I) vs. late-stage (stage IV) cancers were compared based on demographic variables utilizing Chi-square and multivariate analysis with a significance of p < 0.05., Results: Female, Black, and generally older patients were more likely to have late-stage cancer than their counterparts. When compared with a community cancer program, patients treated at other facility types were more likely to be diagnosed late. Patients with private insurance, Medicare, or other government insurance were all less likely to have late-stage cancer compared to patients without insurance. Compared to patients in the lowest median household income quartile, patients in the third quartile and fourth quartile were diagnosed earlier. Patients living in an area with the lowest level of high school degree attainment were most likely to be diagnosed late. Living in a more populous area was associated with a lower chance of being diagnosed late. Increasing Charlson-Deyo Score was associated with a stronger likelihood of being diagnosed at a later stage., Conclusion: Patients who are female, Black, uninsured, have a low household income, live in less populated and less educated areas, are treated at non-community cancer programs, and have more comorbid conditions have later stage diagnoses. This data contributes to understanding inequities in healthcare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: To summarize the recent literature on epidemiology, clinical findings, treatment, and survival of laryngeal verrucous cell carcinoma (LVC)., Recent Findings: Epidemiological studies report that LVC accounts for 1-3% of all laryngeal cancers. The incidence is decreasing, while most patients are male individuals and smokers. LVC are commonly detected in early stages because they are more frequently located in the glottic region. Tobacco, alcohol overuse, and, possibly, human papilloma virus are the main contributing factors. Recent studies confirm that surgery is the primary therapeutic approach with better prognosis when compared with other treatment modalities. Surgery alone is associated with 86.8% disease-free and 80.3% overall survival rates, while metastases are anecdotal., Summary: LVC presents different clinical, pathological, and survival outcomes when compared with the classic laryngeal squamous cell carcinoma. Biopsies need often to be repeated before getting the most appropriate diagnosis; this supports the need of large-sample biopsy during the tumor diagnosis and staging. The glottic location of most LVC leads to detection of this lesion in its early stages, with ensuing better survival and outcomes after surgery compared with the classic form of squamous cell carcinoma. Future studies are needed to understand the biology of LVC and its related better prognostic outcomes when compared to other laryngeal malignancies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Laryngeal cancer epidemiology has changed in recent years, with falling incidence observed internationally. Organ preservation therapies have revolutionised management, though some patients may be unsuitable and survival was noted to fall in the 2000s. This study examines trends in laryngeal cancer in Ireland., Methods: A retrospective cohort study of National Cancer Registry of Ireland data from 1994 to 2014., Results: From a cohort of 2651, glottic disease was most common (62%, n = 1646). Incidence rose to 3.43 cases/100,000/year for 2010-2014. 5-year disease-specific survival (DSS) was 60.6% and did not change significantly over time. Overall survival (OS) for T3 disease managed with primary radiotherapy was similar to primary surgery (HR 0.98, p = 0.9). DSS for T3 disease improved with primary radiotherapy (HR 0.72, p = 0.045)., Conclusion: Incidence of laryngeal cancer in Ireland rose despite international trends, while survival changed little. Radiotherapy improves DSS for T3 disease but does not improve OS, possibly secondary to poor organ function post-radiotherapy., (© 2023. The Author(s).)

Introduction: To determine the incidence, morbidity, and mortality rate of laryngeal cancer in two decades and its epidemiological, clinical, and histological characteristics by sex in Brazil., Methods: This ecological study used three reliable sources of secondary data: population- and hospital-based cancer registries and the national mortality database. All data available from 2000 to 2019 were considered., Results: The incidence of male laryngeal cancer decreased from 9.20 to 4.95 per 100,000 from 2000 to 2018, while mortality slightly decreased from 3.37 to 3.30 per 100,000 from 2000 to 2019. In the same period, the female incidence decreased from 1.26 to 0.48 per 100,000; however, mortality slightly increased from 0.34 to 0.36 per 100,000. Of 221,566 individuals with head and neck cancer, 27 % presented laryngeal cancer. The median age was 61 years (54-69), and most individuals were male (86.6 %), smokers (66.2 %), diagnosed with locally advanced cancer (66.7 %), and squamous cell carcinoma as the main histological type (93.2 %). Male tended to be older (p < 0.001), white (p < 0.001), smokers (p < 0.001), and present late treatment initiation (p < 0.001) and early death (p < 0.001) compared with female., Conclusion: The male laryngeal cancer affected mainly at productive age but with a decreased incidence, probably due to a reduction in smoking habit. However, mortality did not change, which may be explained by the late diagnosis and lack of access to radiotherapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding this subject., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated., Objective: To compare the prognosis of early-stage glottic cancer among SCC variants., Methods: We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants., Results: HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC ( p  < .001 and p  = .032, respectively)., Conclusions: The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC.

Objective: To investigate epidemiological, clinical and oncological outcomes of young patients with laryngeal cancer (LC)., Methods: PubMed, Scopus and Cochrane Library were searched by three researchers for studies investigating epidemiological, clinical and oncological outcomes of patients with age < 40 years old and LC. The following outcomes were investigated with PRISMA criteria: age; ethnicity; gender; tobacco/alcohol habits; anatomical, pathological, therapeutic and survival features. Authors performed a bias analysis of papers and provided recommendations for future studies., Results: Seventeen papers published between 1982 and 2021 met our inclusion criteria, accounting for 928 patients with age < 40 years (female/male ratio: 2:5). There were on average 54.2 and 45.8% of smokers and drinkers. The tumor location mainly consisted of glottis (70.1%), supraglottis (27.7%) and subglottis (2.2%). Radiation therapy was the main therapeutic strategy used in young adults with LC. The 2-year overall survival ranged from 50 to 100% and depended on tumor stage, treatment, and cohort features. Four studies reported better overall survival in young compared with old adults, while there were no significant differences in three studies. There was an important heterogeneity between studies regarding the inclusion/exclusion criteria, epidemiological, clinical, pathological and treatment., Conclusion: It was suggested that young patients with LC had lower proportion of smokers and drinkers and better overall survival compared with older but both data of the current literature and heterogeneity between studies limit us to draw definitive conclusions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A high prevalence and incidence of head and neck tumors make Brazil the country with the third-highest number of cases of these malignant neoplasms. The main risk factors are smoking and alcohol consumption; however, cases related to the human papillomavirus (HPV) have tripled in number, demonstrating a changing disease profile. Studies have reported the prevalence of HPV in laryngeal squamous cell carcinoma (LSCC) to vary between 8% and 83%. The role of HPV as an important causative factor in LSCC remains unclear., Methods: This retrospective study included 82 patients with LSCC diagnosed between 2014 and 2019 at two oncology hospitals in São Luís, Brazil. Sociodemographic and clinical data, and the histopathologic characteristics of the tumors, were collected directly from medical records. Genetic material was extracted from paraffin-embedded samples using nested polymerase chain reaction (PCR) and automated sequencing for HPV detection and genotyping. The results by social and clinicopathologic variables were then compared using the chi-squared test and multivariate analysis., Results: Sociodemographic analysesdemonstrated that most patients were men (87.8%), brown-skinned (75.6%), and resident in the state capital (53.7%). They generally had a poor education status (53.7%), having only an elementary school education (completed/incomplete), and 51.2% were self-employed in occupations such as farming or fishing. Smoking and alcohol consumption habits were observed in approximately half the patients. With respect to clinical characteristics, 39% of patients exhibited T1/T2 staging, 51.2% had no distant metastasis, and 30.5% had lymph node invasion. HPV DNA was detected in half the samples (50%), with the high oncogenic type 16 being the most prevalent. There was no significant relationship observed between the economic, educational, occupational with the HPV LSCC in the presented data, although multivariate analysis demonstrated that HPV DNA was more likely to be present in T3-T4 tumors ( p  = 0.002)., Competing Interests: The authors declare there are no competing interests., (©2022 Brito et al.)

Purpose: To explore the discrepancy in clinicopathological and prognostic features between smoking and alcohol drinking (SA) and non-smoking and non-alcohol drinking (NSNA) patients with laryngeal squamous cell carcinoma (LSCC). Methods: This retrospective study including 1735 patients with LSCC was conducted from January 2005 to December 2010, which were categorized into 4 groups, NSNA group, smoking only group, alcohol-drinking only group, and SA group. We compared overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method and indicated clinicopathological features by Cox proportional hazards regression models before and after propensity score matching (PSM). Results: A total of 415 patients (23.92%) were identified as NSNA. The SA group was predominantly patients ≤60 years old (46.63%) while the NSNA group was more older (58.07%). NSNA group was more likely to present at earlier disease stage and more female. No significant difference in OS ( P  = .685) and DFS ( P  = .976) was found between the 2 groups. In addition to age and recurrence and metastasis being common independent prognostic factors in terms of OS in both groups of patients, NSNA group also exhibited other factors, namely tumor area >3.7 cm 2 and positive resection margin. For DFS, N + stage, tumor size >3.7 cm 2 , and positive resection margin were prognostic features specific to NSNA group. Conclusion: The outcome is similar in LSCC patients with and without SA. NSNA group shows a distinct profile from that found in SA group. Clinicopathological features from NSNA group should be considered for LSCC management.

In the last decade, the incidence and mortality associated with laryngeal malignancies has experienced an unfavorable evolution in Romania, in terms of this pathology the country that has become the leader, among the European Union (EU)-27 countries. The aim of the present retrospective study was to analyze the epidemiological data regarding laryngeal cancer and histopathological (HP) particularities in patients diagnosed in Western Romania. Within three years and 10 months (during October 2016-July 2020) in Ear, Nose and Throat (ENT) Clinic of Timişoara Municipal Emergency Clinical Hospital, 194 patients with laryngeal neoplasms (LN) were diagnosed. Most of the patients were male (93.8%), from Timiş County, mainly and the neighboring Counties of Caraş-Severin, Hunedoara, Mehedinţi and Arad. Patient's average age (both sexes) was 62.6 years, with a range from 38 to 84 years and the highest percentages in the 60+ age group (48%). Regarding smoker status, the main cause of the development of the LN, 93.9% of patients were active ones. Regarding localization [International Classification of Diseases 11th Revision (ICD-11)], about 69% were malignant neoplasm of glottis (C32.0), followed by supraglottis (C32.1), larynx-unspecified (C32.9), and subglottis (C32.2). From the HP point of view, several types of tumors were identified, most of which were non-keratinized and keratinized squamous cell carcinomas (about 90%). In addition, there were identified types of verrucous carcinoma, acantholytic carcinoma, squamous papilloma, a possible pleomorphic sarcoma, and pyogenic granuloma. The data presented in this study highlight the growing incidence of LN, which mainly affect men, at an increasingly young age. It is imperative to involve specialists from nutrition, general medicine, ENT, dentistry to start awareness programs and to develop prevention protocols.

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.

Objectives: The primary objective was to determine the prevalence of synchronous esophageal squamous cell carcinoma in head and neck squamous cell carcinoma (HNSCC) patients. The secondary objective was to determine risk factors for the development of synchronous esophageal squamous cell carcinoma (ESCN)., Study Design: Cross sectional observation study., Methods: A prospective cross sectional, observational study on consecutive 300 newly diagnosed oral cavity, oropharynx, hypopharynx, and laryngeal squamous cell carcinoma patients who underwent trans-nasal esophageal endoscopy with white light imaging and narrow band imaging., Results: Among 300 patients, index HNSCCs were located in the oral cavity (n = 154, 51.3%), oropharynx (n = 63, 21%), larynx (n = 53, 17.7%), and hypopharynx (n = 30, 10%). The prevalence of synchronous ESCN was 2.7% (n = 8), including four low-grade, two high-grade dysplasia, and two squamous cell carcinomas. On logistic regression analysis, moderate to heavy alcohol consumption (OR 8.7, P = .01) and primary HNSCC involving supraglottis [(OR 12.5, P = .02) were risk factors for synchronous ESCN. The association of pyriform sinus carcinoma and synchronous ESCN was of borderline significance (P = .054, OR 10.92)., Conclusion: The prevalence of synchronous ESCN in HNSCC was 2.7%. Routine trans-nasal esophagoscopy should be performed in all newly diagnosed patients with carcinoma of the supraglottis and pyriform sinus, and those with consumption of moderate to heavy alcohol for the screening of synchronous ESCN., Level of Evidence: 2b Laryngoscope, 131:E807-E814, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Laryngeal dysplasia represents a series of precancerous lesions, observed as laryngeal leukoplakia. General agreement has been lacking for their management and treatment ranging from simple biopsy to complete excision with cold blade/laser. In this work, we aim at providing the oncological outcomes of patients affected by laryngeal dysplasia, treated with a single modality, and at identifying clinical parameters predictive of malignant transformation., Materials and Methods: We performed a retrospective analysis of patients treated with transoral laser microsurgery between January 2005 and December 2015 in a tertiary comprehensive cancer centre. Data were collected about smoke and alcohol habits, site of the laryngeal lesion, surgical outcomes and progression to invasive squamous cell carcinoma., Results: The grade of dysplasia, margins' status and smoke habit were not associated with a significantly worse DFS and a higher risk of invasive SCC. We identified three parameters (supraglottic involvement, multifocality and history of more than one recurrence of dysplasia) that have a significant prognostic value., Conclusions: On the base of these clinical parameters, a more intensive follow-up might be warranted for high-risk patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Laryngeal cancer is a common malignancy of the head and neck, especially in northern China, including Shanxi province. This study intends to describe the epidemiological characteristics of laryngeal cancer in Shanxi Province, China, in order to support prevention and treatment efforts., Methods: Retrospective analysis of the medical records of patients diagnosed with laryngeal cancer in hospitals in Shanxi Province from 2008 to 2012., Results: The average annual incidence rate of laryngeal cancer in Shanxi province from 2008 to 2012 was 0.70/10 5 , the Chinese population standardized incidence rate was 0.57/10 5 and the world population standardized incidence rate was 0.60/10 5 . The city with the highest incidence of laryngeal cancer in Shanxi Province is Taiyuan, followed by Yangquan, and the lowest incidence are Yuncheng and Jincheng. The cases included 723 farmers (58.6%), 338 workers (27.4%), 95 government cadres (7.7%), 35 unemployed individuals (2.8%), 30 teachers (2.4%) and 13 individuals with other occupations (1.1%). The incidence of laryngeal cancer in rural areas was 0.78/10 5 , while urban areas was 0.60/10 5 . Of 1006 patients with smoking and drinking status reported, there were 238 both smoking and drinking (23.7%), 491 only smoking but not drinking (48.8%), 4 only drinking but not smoking (0.4%), 273 both not smoking and not drinking (27.1%) (P<0.001), and there were 695 males smoking (95.3%), 34 females smoking (4.7%) (P<0.001). Of 879 patients for whom the primary cancer location was known, 406 cases (46.2%) were supraglottic and 428 cases (48.7%) were glottic. Among 1009 patients with known pathological classification, the vast majority had squamous cell carcinoma (992 cases, 98.3%)., Conclusions: To sum up, the incidence of laryngeal cancer in Shanxi Province exhibited a relatively stable trend from 2008 to 2012, and the incidence is higher in men than in women in all years. The high percentage of smokers in this study underscores the importance of smoking as a risk factor for laryngeal cancer, whereas rates of drinking did not appear to be linked. Incidence of laryngeal cancer was higher in rural areas than in urban areas, a pattern that differs from other regions of China and internationally.

Introduction: Poor oral hygiene, regular use of mouthwash and absence of visits to the dentist could correspond to potential risk factors for the development of head and neck cancer., Objective: The objective of this study was to determine whether oral hygiene is associated with the occurrence of oral cavity and head and neck cancer in a Brazilian sample., Method: The variables of oral hygiene condition, such as toothbrushing frequency, dental loss, need and use of prosthesis, and regular visit to the dentist in a case-control study were analyzed in patients from five hospitals in the state of São Paulo, Brazil, paired by gender and age, from the multicenter project Genoma do Câncer de Cabeça e Pescoço (GENCAPO)., Results: The most frequent malignancies in the 899 patients included were those of the tongue border (11.41%) and tongue base (10.92%). The multivariable statistical analysis found odds ratio values: Brushing once 0.33 (95%CI 0.25 - 0.44); Brushing twice 0.42 (95%CI 0.35 - 0.52); Flossing always 0.19 (95%CI 0.13 - 0.27); Flossing sometimes 0.19 (95%CI 0.15 - 0.24); Bleeding 2.40 (95%CI 1.40 - 4.09); Prosthesis 1.99 (95%CI 1.54 - 2.56); Visiting the dentist 0.29 (95%CI 0.22 - 0.37); Good hygiene 0.21 (95%CI 0.17 - 0.27); Regular hygiene 0.20 (95%CI 0.15 - 0.25); number of missing teeth (6 or more) 3.30 (95%CI 2.67 - 4.08)., Conclusion: These data showed that, in the population studied, indicators of good hygiene such as brushing teeth and flossing were protective factors for mouth and head and neck cancer, while bleeding and many missing teeth were risk factors.

Objectives: Multiple population studies have shown racial discrepancies in head and neck cancer treatment and outcomes. We sought to characterize the impact of race on clinical outcomes for patients with early glottic squamous cell carcinoma (SCC) in a tertiary institution which provides equivalent access to care., Methods: We retrospectively reviewed all early glottic (T1-T2) squamous cell carcinoma at a single institution, the Michael E. DeBakey Veterans' Administration Medical Center (MEDVAMC). Data collected included demographic information, primary and adjuvant treatment modalities, time to diagnosis, time to treatment, recurrences, recurrence treatment modality, secondary malignancies, recurrence-free survival (RFS), and overall survival (OS)., Results: One hundred seventeen patients with a primary diagnosis of T1-T2 glottic squamous cell carcinoma were included. Black and white patients demonstrated equivalent rates of recurrence, RFS, and OS. There was no significant difference in treatment delivery by race for all recorded parameters. T1b tumors were associated with an increased risk of recurrence which did not translate into a statistically significant decrease in RFS or OS. Surgical treatment was associated with increased recurrence but similar RFS and OS compared to radiation-based treatment. Secondary malignancies were common; 12% of patients were diagnosed with a second primary lung cancer during the study period., Conclusion: At our institution, race did not impact survival when access to care, treatment selection, and delivery are equivalent for early glottic SCC. Secondary lung cancer is a critical risk factor for mortality in this patient group and requires long-term surveillance and monitoring., Level of Evidence: 4 Laryngoscope, 130:1733-1739, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Advanced laryngeal squamous cell carcinoma remains associated with approximately 50% mortality at 5 years. Delivery of multimodality treatment remains critical to maximizing survival for this disease, but achieving this at a national level remains a difficult undertaking, particularly in under- and uninsured patients as well as minority patients. We sought to evaluate laryngeal cancer treatment delivery and clinical outcomes in a predominantly minority and underserved cohort of largely under- and uninsured patients in a county hospital., Study Design: Retrospective cohort study., Setting: Tertiary care county hospital in Houston, Texas., Subjects and Methods: Patients (N = 210) with a new diagnosis of laryngeal squamous cell carcinoma treated between 2005 and 2015 were included in a retrospective analysis of patient demographics, tumor and treatment characteristics, and oncologic outcomes., Results: The majority of patients presented with advanced disease (T4 = 43%, N>0 = 45%). Treatment selection was compliant with National Comprehensive Cancer Network guidelines in 81% of cases, but 76% of patients who required adjuvant radiotherapy were unable to start it within 6 weeks postsurgery. Overall survival and disease-free survival were 52% and 63% for the entire cohort, respectively. Supraglottic subsite and nodal metastases were significantly associated with decreased overall survival and disease-free survival. Race/ethnicity and insurance status were not associated with worse oncologic outcomes., Conclusion: Under- and uninsured patients often present with advanced laryngeal cancer. Oncologic outcomes in this cohort of patients is similar to that of other published series. Moreover, tumor characteristics rather than demographic variables drive oncologic outcomes for the predominantly minority and underserved patients seeking care in our tertiary care county hospital.

Objective: Firefighters are exposed to a wide variety of carcinogens during the line of duty, including several associated with head and neck cancer. Existing studies assessing head and neck cancer risk with firefighting have predominately included occupational cohorts or registry data, which are limited by inability to adjust for smoking and alcohol consumption-major risk factors for head and neck cancer. Our objective was to assess the risk of head and neck cancer among men with an occupational history as a firefighter., Methods: This work was conducted using male subjects from a large population-based case-control study of head and neck cancer from the greater Boston area using self-reported occupational history (718 cases and 905 controls)., Results: An occupational history as a firefighter was reported for 11 cases and 14 controls. Although no significant association was observed overall, we observed substantial increased risk for hypopharyngeal and laryngeal squamous cell carcinoma among professional municipal firefighters who had a light or no smoking history (OR=8.06, 95% CI 1.74 to 37.41), with significantly increasing risk per decade as a firefighter (OR=2.10, 95% CI 1.06 to 4.14)., Conclusion: Professional municipal firefighters may be at increased risk for hypopharyngeal and laryngeal squamous cell carcinoma due to carcinogenic exposures encountered during the line of duty., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives/hypothesis: Laryngeal squamous cell carcinoma (SCC) is strongly associated with tobacco smoking. With the rising awareness of tobacco's adverse health effects, we have witnessed a global decrease in tobacco use. Nevertheless, laryngeal SCC remains prevalent and includes a subset of patients lacking the traditional risk factors., Study Design: A two-center retrospective cohort., Methods: Medical records of patients diagnosed with laryngeal SCC between 2009 and 2016 were reviewed. Data collected included demographics, smoking status, and tumor site. Patients who have never smoked were designated as nonsmokers., Results: The study included 330 patients with laryngeal SCC, of whom 75 (22.7%) were nonsmokers; this rate was relatively similar for each of the two institutions independently (21.9% and 25%). There were 285 patients with glottic SCC and 45 with supraglottic SCC. All nonsmoking patients in this cohort had glottic SCC, representing 26.3% (75/285) of the glottic SCC cases. The rate of female patients was significantly higher among nonsmokers. Of the patients with glottic SCC, females represented 25.3% (19/75) of the nonsmokers compared with 12.4% (26/210) of the smokers (P = .008). Mean age at diagnosis was 60.2 ± 17.5 years for nonsmoking glottic SCC patients and 63.6 ± 12.4 years for smokers (P = .280). However, nonsmokers demonstrated a distinct age distribution pattern. Nonsmoking females with glottic SCC demonstrated a bimodal age distribution pattern; 73.7% (14/19) were age <40 years or >75 years at diagnosis., Conclusions: The rate of laryngeal SCC in nonsmokers is higher than what has previously been reported, representing a growing proportion, and may suggest a shift in etiology. Knowing that laryngeal SCC in nonsmokers predominantly affects the glottis, and that females and age extremities are more vulnerable, the traditional screening paradigm should be revised., Level of Evidence: 4 Laryngoscope, 130:E108-E115, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background/purpose: To examine whether the prevalence rate of human papillomavirus (HPV) infection in Taiwanese patients with primary laryngeal squamous cell carcinoma (LSCC) is different from that in those with a vocal polyp (VP) or vocal fold leukoplakia (VFL)., Methods: This prospective cohort study recruited 41 consecutive patients with primary LSCC and 27 and 20 patients with VP and VFL, respectively. The HPV L1 gene in surgical specimens was detected using polymerase chain reaction. High-risk HPV DNA in tissue microarray specimens was detected using in situ hybridization. Expression of p16 INK4a in tissue microarray specimens was determined through immunohistochemistry., Results: The prevalence of HPV L1 DNA in the LSCC group was equivalent to that in the VP and VFL groups (7.3% vs. 7.4% vs. 10.0%; P = 0.929; effect size = 0.20). High-risk HPV DNA detected using in situ hybridization was relatively rare in all groups (2.6% vs. 5.3% vs. 0.0%; P = 0.636; effect size = 0.81). The prevalence of p16 INK4a positivity was significantly lower in the LSCC group than in the VP and VFL groups (5.1% vs. 58.8% vs. 14.3%; P < 0.001). Multivariate analysis results revealed that age ≥65 years (adjusted odds ratio, 4.09; 95% confidence interval, 1.21-13.91; P = 0.024) and p16 INK4a positivity (adjusted odds ratio, 0.10; 95% confidence interval, 0.02-0.53; P = 0.006) were LSCC risk factors., Conclusion: HPV infection is uncommon in Taiwanese patients with LSCC and seems not to be associated with an increased LSCC risk. Larger sample size is warranted for further study., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Laryngeal cancer is the most common head-and-neck malignancies with more than 20% of all cases. The vast majority of tumors are squamous cell carcinoma (SCC). Several genes encoding different cytokines may play crucial roles in host susceptibility to cancer because cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms., Materials and Methods: The association between cytokine gene polymorphisms with primary laryngeal SCC was investigated. DNA samples were obtained from a Turkish population of eighty patients with primary cancer and fifty healthy controls., Results: All genotyping (interferon-gamma, transforming growth factor-β1 [TGF-β1], tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, and IL-10) experiments were performed using polymerase chain reaction sequence-specific primers. When compared to the healthy controls, the frequencies of TGF-β1 codon 25 (rs1800471) GC genotype and 25 C allele were significantly more common in the patient group., Conclusions: These results suggest that TGF-β1 gene polymorphisms may affect host susceptibility to laryngeal cancer., Competing Interests: None

Objectives: Human papillomavirus (HPV) can be detected in approximately 25% of squamous cell carcinomas (SCC) of the larynx and hypopharynx. Though HPV is associated with improved survival and disease control in patients with oropharyngeal SCC, the role of HPV as a marker of favorable treatment outcomes in laryngeal and hypopharyngeal cancer is unclear., Materials and Methods: Patients treated for laryngeal or hypopharyngeal SCC were reviewed. HPV status detected by p16 and/or HPV DNA PCR were abstracted from the medical record. A subset of samples (stage III-IV treated with primary radiotherapy) was retrospectively tested for p16 and HPV DNA. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were determined and compared between HPV-positive (p16+, PCR+ or both) and HPV-negative (p16- or PCR-) patients., Results: In total, 279 patients were identified, 94 of which were tested for HPV. Eighty-two (87%) were negative and 12 (13%) were positive for HPV. At 3 years, there were no significant differences in OS (72% v. 83%), DFS (60% v. 71%) and LRC (80% v. 89%). Performance status, smoking history and stage predicted for OS, while performance status and stage predicted for DFS. Analysis of patients treated with primary radiotherapy revealed non-significantly higher rates of laryngeal preservation at 3 years (75% v. 100%)., Conclusion: HPV was detected in 13% of tested laryngeal/hypopharyngeal cancers. HPV does not appear to significantly impact survival or disease control in patients with SCC of the larynx or hypopharynx. Non-significant improvements in laryngeal preservation were observed in HPV-positive patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The upper aerodigestive tract (UAT) includes the nose and paranasal sinuses, oral cavity, pharynx, larynx, and salivary glands. Cancers of the UAT constitute approximately 4% of all malignancies. In this study, the varied nature of the UAT cancers was studied to find out their incidence, etiology, and clinicopathological correlations., Materials and Methods: This prospective, observational, and clinicopathological study was conducted on 100 patients who were presented at outdoor in the Department of ENT, Government Medical College/Rajindra Hospital, Patiala, Punjab, India, from October 2016 to October 2018. Proven cases of UAT cancers were taken up and reviewed to gather data on multiple clinicopathological variables, such as age, sex, predisposing factors, and site of pathology. Histopathological differentiation was noted after conducting a biopsy., Results: Most patients of UAT cancers were in the age group of 40-70 years. Maximum incidence was among males (82%) compared to females (28%). The most common predisposing factor was alcohol + smoking (28%), followed by alcohol + chewing tobacco (25%). The most common symptom in the oral cavity was ulcer and odynophagia (38%) each. In oropharyngeal cancers, dysphagia (92%) was the most common symptom. In laryngeal cancers, dyspnea (68%) and hoarseness of voice (32%) were the most common. The most common site involved in UAT cancers was the oral cavity (31%), followed by oropharynx (28%), larynx (22%), hypopharynx (7%), and salivary gland (5%). The most common histopathological type was squamous cell carcinoma (SCC) (90%). Most of the ulceroproliferative and exophytic growth was moderately differentiated SCC on histopathology., Conclusion: Studies are essential for education and awareness aimed at reducing exposure to habit-forming substances., Competing Interests: None

Objective: To investigate the role of human papillomavirus (HPV) in laryngeal squamous cell carcinoma (LSCC) and analyse the relationship between HPV and the expression of cell cycle-related proteins., Design: The study consisted of LSCC between 2005 and 2011 in Tongren Hospital. Clinical data such as age, sex, smoking/alcohol consumption, and TNM stage were collected. HPV DNA and cell cycle-related proteins were assessed in terms of clinical features., Setting: Single-centre study., Participants: A total of 332 LSCC patients were included in the study., Main Outcome Measures: The presence of genotype-specific HPV DNA was evaluated using PCR-RDB in formalin-fixed paraffin-embedded tissues. All samples were also evaluated for p16 INK4A , p21 WAF1/CIP1 , P53, Cyclin D1, and Ki67 immunohistochemical staining by tissue microarray., Results: HPV DNA was detected in 45 of 332 (13.55%) patients with LSCC, with HPV-16 being the predominant genotype. The presence of HPV-16 DNA was significantly associated with basaloid squamous cell carcinoma and cystic lymph node metastasis (P < 0.05). Of the 332 patients, 36 (10.84%) were scored as p16 INK4A positivity and they were more likely to be female (P < 0.05). Cyclin D1-positivity and p21 WAF1/CIP1 -positivity were observed in 60.24% (200/332) and 40.66% (135/332), respectively. In 114 cases (34.33%), LSCCs had moderate- to -strong p53 accumulation, which was correlated with TNM stage (P < 0.05). HPV-16 DNA was correlated with p16 INK4A and manifested a higher Ki-67 labelling index and p21 WAF1/CIP1 expression than HPV-16-negative tumours (P < 0.05). No relationship was observed between Cyclin D1or P53 expression and HPV-16 infection (P > 0.05)., Conclusion: HPV DNA was detected in 13.55% patients with LSCC, with HPV-16 being the predominant genotype and it was correlated with p16 INK4A and manifested a higher Ki-67 labelling index and p21 WAF1/CIP1 expression than HPV-16-negative tumours., (© 2019 John Wiley & Sons Ltd.)

Purpose: The study analysed the presence of HPV in samples tissue from laryngeal chronic hyperplastic inflammation, with and without pre-neoplastic potential, and from squamous cell carcinoma of the larynx. The aim of this analysis was to evaluate the presence/absence of different types of HPV and their relationship to the clinical profile of the patients studied (habit of smoking and drinking)., Methods: Sixty cases were randomly selected from patients undergoing surgical treatment of the larynx for inflammatory/ neoplastic lesions and of neck nodes. Patients underwent standard clinical workup, comprising medical history and physical examination, panendoscopy, whole-body CT scan (in cancer patients), diagnostic or therapeutic microlaryngoscopy with laryngeal biopsy, and HPV evaluation., Results: The HPV analysis showed an increased risk for heavy smokers of HPV positivity, as well as precancer lesions and cancer. Type 6 and 16 seem to be prevalent in all types of laryngeal mucosa disease, but pre-neoplastic conditions versus cancer seem to show a wider variety of HPV infections while cancer patients are invariably affected by types 6 and 66. Heavy smoking is related to HPV infection likewise alcohol in association with smoking. Advanced T is more associated with HPV positivity., Conclusions: These data impose a closer follow-up of smokers and pre-neoplastic cases and the utility of the broadspectrum polymerase chain reaction assay in laryngeal dysplastic and cancer lesions. This study may allow to develop biomarkers for early detection or recurrence surveillance, to identify therapeutic targets, and to begin individualization of treatment based on the biology of these tumours., Key Words: HPV infection, Larynx, Laryngeal chronic hyperplastic inflammation, Squamous cell carcinoma.

Objective: Subglottic squamous cell carcinoma is a rare subsite of laryngeal cancer that behaves more aggressively and portends a worse prognosis. Using a population-based cancer registry, our objective was to report overall survival (os) and laryngectomy-free survival (lfs) in patients diagnosed with subglottic squamous cell carcinoma, and to determine whether primary laryngectomy results in improved survival., Methods: This retrospective population-based study considered patients with a new diagnosis of squamous cell carcinoma in the province of Ontario over a 15-year period (1995-2009). The Ontario Cancer Registry was examined for patients with the diagnosis of interest during the period of interest. Linked population-based databases were used to obtain patient demographics, comorbidity measures, staging, survival, and primary treatment with laryngectomy., Results: Of 4927 patients identified to have laryngeal carcinoma, 89 were defined as having primary subglottic carcinoma (1.8%). In the subglottic cohort, 68 patients were men (76.4%), and mean age at diagnosis was 68 years (interquartile range: 60-77 years). The 5-year os was 47.2%, and the 5-year lfs was 31.5%. In 13 patients (15%), the primary treatment was laryngectomy, which, compared with primary radiation, did not predict for improved os. No differences in os or lfs were observed during the 15-year study period (os p = 0.42, lfs p = 0.83)., Conclusions: The survival of patients with subglottic carcinoma is poor and has remained stable over time (1995-2009). Compared with primary radiation, primary treatment with laryngectomy does not appear to improve os., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

Background: Leukoplakia of the vocal cords may represent a pre-cancerous lesion of the larynx. The management of cases of recurrent leukoplakia with pathologically proven dysplasia is still controversial., Objectives: To present a series of patients with recurrent vocal cord leukoplakia and to examine their malignant transformation rate in relation to the clinical characteristics, risk factors, and histological findings., Methods: A retrospective cohort study was conducted between 1999 and 2017. The study comprised 52 patients with recurrent leukoplakia of the vocal cords who required ≥ 2 direct laryngeal procedures within a minimum of 3 months between each procedure. Malignant transformation rate over follow-up period, risk factors for malignant transformation, and interval to develop laryngeal squamous cell carcinoma were investigated., Results: All patients presented with hoarseness. An average of three procedures per patient was performed (range 2-13). Ten male patients (19.2%) developed squamous cell carcinoma. Of these, four with severe dysplasia developed SCC within 19 months of the first direct laryngoscopy. In the six other patients, SCC developed within an average of 3.7 years. The follow-up period ranged from 9-253 months (mean 109 months). Heavy smoking and severe dysplasia in the first biopsy were found to be significant risk factors for developing squamous cell carcinoma, as was male gender., Conclusions: We showed an increased malignant transformation rate in recurrent leukoplakia cases among heavy smokers and male patients. In addition, severe dysplasia at initial diagnosis was a risk factor for SCC development. Close follow-up of patients with recurrent leukoplakia is warranted.

To delineate the role of human papillomavirus (HPV) in laryngeal cancer in Southern Chinese, a retrospective cross-sectional study was conducted in a major otorhinolaryngology referral center in Hong Kong. Eighty-five Chinese patients with histology-confirmed laryngeal squamous cell carcinoma (LSCC) diagnosed between 2005 and 2010 were examined for the status of HPV by PCR, and the expression of p16 and p53 by immunohistochemistry. The HPV, p16 and p53 findings were correlated with clinicopathological features, recurrence and 5-year survival. HPV DNA was detected in one patient (1.2%, 95%CI: 0.2-6.4%) who had glottic cancer and harbored HPV-6. Overexpression of p16 and p53 were detected in 11 (12.9%) and 47 (55.3%) cases, respectively. Recurrence occurred in 22.4% of patients at a median of 13 months. The 5-year overall survival and disease-specific survival were 55.7% and 72.4%, respectively. Overexpression of p16 or p53 was not associated with clinicopathological features, recurrence or overall survival. HPV plays a limited role in laryngeal cancer in Hong Kong Southern Chinese. In contrast to oropharyngeal cancer, p16 cannot be used as a surrogate marker for oncogenic involvement of HPV and cannot predict survival in laryngeal cancer., (© 2018 Wiley Periodicals, Inc.)

Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer., Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015., Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p=0.004). In multivariate analysis, age <70years (p=0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p=0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer., Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Intravenous opioid drug abuse (IVDA) was previously correlated with laryngeal cancer. However, discrimination of this correlation by anatomical subsites has not yet been described. In this study, we aim to further establish the association between IVDA and laryngeal squamous cell carcinoma (SCC) and to indicate the laryngeal subsites that are predisposed for this correlation., Design: A retrospective matched case-control study., Setting and Participants: Patients diagnosed with supraglottic SCC (SG-SCC) between 1996 and 2016 treated in a tertiary academic referral centre were enrolled to the case group. The control group comprised of matched patients diagnosed with glottis SCC (G-SCC). Matching was based on gender, age and socio-economic rank., Main Outcome Measures: Variables studies as risk factors included the following: smoking, alcohol consumption, history of IVDA and infectious diseases. The variables were tested for association with the 2 groups and with each other., Results: Forty-eight patients with SG-SCC were matched with 48 patients with G-SCC. IVDA rates significantly increased among patients with SG-SCC. Of the SG-SCC group, 18.8% had a positive history for IVDA compared with 2.1% of the G-SCC (P = .008). A history of IVDA was found to be a risk factor for SG-SCC, independent of smoking, excessive alcohol and socio-economic status. The odds ratio for patients with an IVDA history to have SG-SCC relatively to G-SCC was 10.846 (95% CI: 1.3-89.4)., Conclusions: Intravenous opioid drug abuse represents an independent risk factor for SG-SCC. The pathogenesis should be investigated not just as a risk factor, as opioids are commonly used for pain management in oncologic patients., (© 2017 John Wiley & Sons Ltd.)

Objective: To assess the prevalence of human papillomavirus (HPV) in benign and malignant laryngeal lesions among Egyptian patients., Design: Observational analytical cross-sectional study., Setting: Ain Shams University hospital, Otorhinolaryngology department PARTICIPANTS: Formalin-fixed paraffin-embedded specimens of 126 patients (70 benign laryngeal lesions and 56 squamous cell carcinoma lesions) were assessed for the presence of HPV DNA using MY09/11 PCR-based DNA detection., Main Outcome Measures: Percentage of positive samples was calculated., Results: All 70 benign laryngeal lesion specimens were negative for the HPV DNA, while 2 of the 56 squamous cell carcinoma lesions (3.6%) were positive., Conclusions: The presence of HPV DNA in only two specimens in our study suggests that the proportion of laryngeal squamous cell carcinomas attributable to infection by HPV seems to be very low in Egypt., (© 2017 John Wiley & Sons Ltd.)

Background/aims: Human papillomavirus (HPV) is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. Here, we sought to evaluate the prevalence and genotype distribution of HPV in patients with laryngeal squamous cell carcinoma (LSCC) in northeast China., Methods: HPV DNA in specimens from 211 patients diagnosed with LSCC was analyzed by the polymerase chain reaction and in situ hybridization, and p16 overexpression was evaluated by immunohistochemistry. p16 expression was scored positive if strong and diffuse nuclear and cytoplasmic staining was present in > 75% of tumor cells., Results: In this study, infection with HPV and p16 expression were not absolutely consistent. Among all patients, 132 (62.6%) were positive for HPV DNA (HPV+), while 23 (10.9%) were inconsistent for HPV and p16. Multivariate analysis indicated that HPV, but not p16, is an independent prognostic factor for overall survival in LSCC. Overall survival was significantly improved in HPV+ LSCC patients compared with the HPV-negative group (hazard ratio, 0.395; 95% confidence interval, 0.185-0.843; p = 0.016). Among the 132 HPV+ patients, 28 (21.2%) were HPV-16 single infection., Conclusion: This study indicates that HPV DNA is a more reliable surrogate marker than p16 for the prediction of survival in patients with LSCC., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Introduction: It is estimated that around 10% of all head and neck cancer patients in India are aged over 70 years. Elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy. In this study we evaluated our use of radical radiotherapy in carcinoma larynx for patients over seventy years of age to determine morbidity, likelihood of completing therapy, functional and oncological outcomes., Materials and Methods: 132 patients of squamous cell carcinoma of the larynx treated between 2005-2015 at Amrita Institute of Medical Sciences, Kochi who were seventy years of age or older were included. The endpoint for analysis was overall survival. Survival curves were generated using Kaplan Meier method and univariable analysis was performed using log rank test., Results: The median age of patients was 77 years (range 70-102). All patients (100%) completed radiotherapy with 6 (5%) requiring treatment breaks. All patients had at least minor (grade I/II) toxicities. Grade III toxicities were seen in 10 (8%) of patients. No grade IV reactions or treatment related deaths occurred. When a univariate analysis was performed for determinants of major toxicities with age range, performance status, smoking, number of co-morbidities or TNM stage, no determinants were statistically significant. 2-year disease free survival for stage I, II, III and IV was 100%, 98%, 80% and 64% respectively, and the 2-year overall survival for all four stages was 100%., Conclusion: Patients over seventy years tolerate radical radiotherapy for treatment of laryngeal cancer. In spite of minor toxicities, all patients completed treatment and had good oncological outcomes. Patients with stage III/IV unfit for concomitant chemotherapy administration treated with radiotherapy alone had a good disease free survival. Curative intent therapy should not be withheld from elderly patients on the basis of age., Competing Interests: There are no conflicts of interest

The aim of the present study was to evaluate the role of HPV in laryngeal squamous cell carcinoma and correlate it with patients' clinicopathological data. In total, 78 laryngeal squamous cell carcinoma patients enrolled in this study. The presence of genotype-specific HPV DNA was evaluated using Genotyping Assay in formalin-fixed paraffin-embedded tissue which was diagnosed between 2005 and 2015. All samples were also evaluated for p16 immunohistochemical staining. HPV DNA and p16 status were assessed in terms of location, smoking, alcohol consumption, lymph node status, tumor stage, overall survival, disease-free survival, perineural invasion, and vascular invasion retrospectively. Five test samples were excluded from the study due to inadequate deoxyribonucleic acid purity. HPV DNA was detected in 19 of 73 (26.02%) in patients with laryngeal squamous cell carcinoma. Human papilloma virus genotyping revealed double human papilloma virus in one case (types 16 and 59) and HPV 16 in the remaining cases. Although HPV-positive cases showed slightly better 3 years survival than HPV-negative ones, this finding was not statistically significant (overall survival p = 0.417, HPV positive: 92.3%, HPV negative: 81.4%, and disease-free survival p = 0.526, HPV positive: 93.8%, HPV negative: 80.9%). The presence of HPV DNA was not significantly associated with any clinicopathological features (p > 0.05). Among 73 patients, only 4 had an immunohistochemical staining of p16 and these patients were also HPV DNA 16 positive. Although our study results revealed a slightly better survival in patients with HPV DNA positivity for HPV 16 compared to the negative ones, the difference was not statistically significant. However, an increasing rate in especially high-risk-type HPV-16 prevalence in laryngeal squamous cell carcinoma by RT-PCR method was observed compared to our previous study. Although the presence of HPV in laryngeal SCCs seems to be associated with slightly better prognosis, additional studies may be needed, since our results were not statistically significant. We believed that HPV is not an adequate biomarker for diagnostic and prognostic purposes in laryngeal squamous cell carcinoma.

Objective: Thrombocytosis is commonly observed in patients with solid tumors. This study aimed to evaluate the prognostic role of circulating pretreatment platelet count in a large series of patients with head and neck squamous cell carcinoma (HNSCC)., Methods: We retrospectively studied 824 patients with HNSCC treated at a single institution from 2000 to 2012. Disease-specific survival and local, regional, and distant recurrence-free survival were analyzed according to the distribution of the platelet count., Results: By defining the platelet count 250.05×10 9 /L as a cut-off point with the best predictive capacity, we classified the patients into two groups: those with a high platelet count (n=378, 45.9%), and those with a low platelet count (n=446, 54.1%). On univariate analysis, there were significant differences in disease-specific survival depending on pretreatment platelet count (P=0.001). The 5-year specific survival rates were 74.1% (CI 95%: 69.8-78.4%) and 61.6% (CI 95%: 56.4-66.8%) for patients with a low and high platelet count, respectively. According to the results of a multivariate analysis, patients with a high count of platelets had a tendency to a lower disease-specific survival, but the hazard ratio did not reach statistically significant differences (HR 1.24, CI 95%: 0.97-1.61, P=0.085)., Conclusion: Platelet count was significantly associated with survival in univariate analysis. However, in a multivariate analysis it lost its prognostic capacity, limiting its utility as a prognostic marker in patients with HNSCC. Considering separately each primary tumor location, patients with hypopharyngeal cancer and a high platelet count had a significant decrease of disease-specific survival., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Neck dissection for laryngeal squamous cell carcinoma (LSCC) patients could provide complementary prognostic information for AJCC N staging, like lymph node ratio (LNR). The aim of this study was to develop effective nomograms to better predict survival for LSCC patients treated with neck dissection., Results: 2752 patients were identified and randomly divided into training (n = 2477) and validation (n = 275) cohorts. The 3- and 5-year probabilities of cancer-specific mortality (CSM) were 30.1% and 37.2% while 3- and 5-year death resulting from other causes (DROC) rate were 6.2% and 11.3%, respectively. 13 significant prognostic factors including LNR for overall (OS) and 12 (except race) for CSS were enrolled in the nomograms. Concordance index as a commonly used indicator of predictive performance, showed the nomograms had superiority over the no-LNR models and TNM classification (Training-cohort: OS: 0.713 vs 0.703 vs 0.667, CSS: 0.725 vs 0.713 vs 0.688; Validation-cohort: OS: 0.704 vs 0.690 vs 0.658, cancer-specific survival (CSS): 0.709 vs 0.693 vs 0.672). All calibration plots revealed good agreement between nomogram prediction and actual survival., Materials and Methods: We identified LSCC patients undergoing neck dissection diagnosed between 1988 and 2008 from Surveillance, Epidemiology, and End Results (SEER) database. Optimal cutoff points were determined by X-tile program. Cumulative incidence function was used to analyze cancer-specific mortality (CSM) and death resulting from other causes (DROC). Significant predictive factors were used to establish nomograms estimating overall (OS) and cancer-specific survival (CSS). The nomograms were bootstrapped validated both internally and externally., Conclusions: Comprehensive nomograms were constructed to predict OS and CSS for LSCC patients treated with neck dissection more accurately.

Background: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival., Methods: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated., Results: Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase β (POLB) gene (false discovery rate [FDR] < 0.01). The homozygous/heterozygous genotypes containing the African allele showed higher POLB expression than the homozygous white allele genotype (P < .001). A replication study using a GEO data set validated all 5 eQTLs and also showed a statistically significant difference in POLB expression based on genetic ancestry (P = .002). An association was observed between these eQTLs and OS (P < .037; FDR < 0.0363) as well as DFS (P = .018 to .0629; FDR < 0.079) for oral cavity and laryngeal cancer patients treated with platinum-based chemotherapy and/or radiotherapy. Genotypes containing the African allele were associated with poor OS/DFS in comparison with homozygous genotypes harboring the white allele., Conclusions: Analyses show that ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. Cancer 2017;123:849-60. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Introduction: Pediatric head and neck Squamous cell carcinoma (PHNSCC) is a rare disease. The optimum treatment and outcome remains poorly understood because of rarity., Methods: We conducted an individual patient data analysis of PHNSCC. Two authors independently searched PubMed, google search, and Cochrane library for eligible studies using following search words: Pediatric Head and neck squamous cell carcinoma, Head and neck squamous cell carcinoma under age of 20, Head and neck squamous cell carcinoma in young, PHNSCC till June 1, 2016 published in English language., Results: Total of 217 patients of PHNSCC were found in the literature. Median age among the cohort was 15 years (Range: 0-20 years) with a clear male preponderance. Oral cavity tumors were commonest 75 (70%) followed by laryngeal neoplasms 16(15%). Median disease free survival was 9 months (Range: 0-216 months). Median overall survival was 48 months (Range: 1-216 months). In univariate analysis treatment modality had significant impact on disease free survival (DFS). Whereas, patients treated with Surgery, Laryngeal primary had significantly better OS. Patients with associated fanconis anemia had significantly worse overall survival (OS)., Conclusion: PHNSCC is a rare disease with poorer outcome. Associated DNA defects leads to poorer OS. Patients treated with surgery alone or surgery followed by adjuvant radiation had better DFS and OS. Molecular profiling and personalized therapy may improve survival with limited toxicity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

A strong and consistent association has been reported between human papillomavirus (HPV) infection and oropharyngeal cancer, whereas a similar link has not yet been clarified in oral and laryngeal cancer. The purpose of this study was to investigate the association between HPV infection and head and neck squamous cell carcinoma (HNSCC) in Greek patients. Cytological or tissue specimens from 172 cases patients with HNSCC and cytological specimens from 91 control subjects were analyzed for HPV DNA detection and genotyping using a microarray-based assay. Multivariate logistic regression was used to estimate odds ratios (ORs) for the association between the presence of HPV infection and HNSCC for each of the tumor site, after adjustment for potential confounders. The adjusted ORs for positivity to high-risk HPV infection for oropharyngeal and laryngeal cancer were 20.3 (95% CI: 1.7-250.1) and 22.8 (95% CI: 2.5-206.2), respectively. High-risk HPV infection was not significantly associated with oral cancer. HPV infection was independently associated with poorly differentiated tumors (OR = 2.8; 95% CI: 1.1-7.5). Our results suggest a strong association of high-risk HPV infection with oropharyngeal and laryngeal cancer. J. Med. Virol. 89:170-176, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

For decades, the standard of care for radiation treatment of early larynx cancers has been conventional treatment using opposed lateral fields encompassing the larynx and overlying neck structures, including the adjacent carotid arteries. While intensity-modulated radiotherapy (IMRT) has replaced conventional radiotherapy for all other head/neck cancer situations, the use of IMRT to treat early glottic cancers remains controversial. The article reviews the published experience with IMRT for this clinical situation and provides a detailed review of the literature on radiation-induced carotid toxicity and how it might apply to the controversy. Finally, we discuss whether the radiation oncology community should transition to IMRT as a new standard of care for the treatment of early glottic cancers.

Background: Cancer of the head and neck comprises a group of neoplasms that share a similar anatomical origin. Most originate from the epithelium of the aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by human papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11 in laryngeal cancer. There are reports in the literature that show HPV as the leading cause of oropharyngeal squamous cell carcinoma., Objective: Determine the prevalence of infection with high-risk HPV in patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx and larynx., Material and Methods: An observational, cross-sectional, descriptive, unblinded study was performed. Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in DNA samples from tumour tissue of patients with squamous cell carcinoma of the oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV positive samples in order to detect types 18, 16, 11 and 6, using custom primers., Results: A total of 45 patients were included. The association between laryngeal squamous cell carcinoma and HPV was established in two patients, which represented an overall prevalence of 4.4% in our population, and 10% for laringeal tumours., Conclusions: There is a low prevalence of HPV infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our population. Prospective studies on younger patients could provide more information., (Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.)

The cartilaginous invasion determines the T and is one of the most common sources of mistake in tumor staging. Also it is of great importance when planning any therapeutic alternative. In the latest revision of the TNM classification a clear distinction is made between infiltration of cartilage without going through it, considered a T3 recently and that would be a T4 according to the previous classification, and those going through the cartilage, classified as T4a. While this classification makes the difference in depth of infiltration, it does not emphasize the extent of invasion. This paper provides a detailed description of the laryngeal cartilage tumor infiltration by whole organ serial section in which the invasion is considered both horizontal (transcartilaginous) and vertical (extent of invasion) and establishing patterns of three-dimensional infiltration of the cartilage. This is a cross-sectional study of prevalence. 275 records of patients treated for laryngeal squamous cell carcinoma between 1995 and 2000 were reviewed. The pathological processing of laryngectomy surgical specimens was performed following the method of whole organ serial section described by G. F. Tucker. The following patterns of cartilaginous infiltration were defined: (1) transcartilaginous infiltration; (2a) partial focal infiltration of the cartilage: infiltration not going through the cartilage but occupying one third or less of its extent; (2b) partial extensive infiltration of the cartilage: infiltration occupying two thirds or more of its length and (3) no cartilage infiltration: tumor in contact with the cartilage (paraglottic space) but without affecting it. 161 patients met the inclusion criteria. The most frequent tumor location was supraglottic (58 cases) followed by glottic (47). 109 patients (67.7 %) were treated with total laryngectomy. Partial surgical techniques were performed in the remaining cases. TNM tumor staging was performed according to the results of pathological study (pTNM). 72.06 % (116) were classified as advanced laryngeal tumors (pT3 and pT4). 46 % of patients showed some extent of laryngeal cartilage infiltration (thyroid, cricoid, arytenoids, epiglottis). The cartilage most frequently infiltrated was the thyroid in 48 patients (29.8 %) and when it is affected, in most cases (66.7 %), the infiltration is transcartilaginous. The next most common pattern is partial focal infiltration (27 %). In the cricoid cartilage, the most common pattern of infiltration is focal partial infiltration (52.6 %). Of the 19 cases with infiltration of the cricoid, there are 12 cases with extra laryngeal invasion through a cricothyroid membrane perforation. The study of laryngeal cancer by laryngeal whole serial section has been proved to be very useful in offering a high precision pTNM staging and a detailed description of the infiltration of cartilage. We have seen that when the thyroid cartilage is infiltrated the tumor often passes through the cartilage. However, there are cases where the tumor is extremely aggressive, being very widespread in cartilage thickness without actually crossing it. The isolated infiltration of the cricoid cartilage is exceptional.

Objective: Conventional wisdom is that the overwhelming majority of glottic cancer patients have a smoking history. However, in recent years observations suggested that an increasing number of glottic cancer patients had never been smokers. Therefore, an investigation was done examining the incidence of having a smoking history in a recent cohort of glottic cancer patients., Method: Retrospective review of 100 patients with glottic cancer to determine those reporting never having smoked., Results: Thirty-one of 100 did not have a smoking history. Clinical observations of those cases revealed that the disease morphology tended to be exophytic, papillary, and very vascular, often resembling recurrent respiratory papillomatosis (RRP). Remarkably, 2 of 31 were initially treated elsewhere assuming they had RRP and underwent 5 cidofovir injections. Both presented with advanced cancer, and the disease growth markedly accelerated coincident with the injections., Conclusions: Observations herein provide new insights that glottic cancer may be an evolving disease in which smoking is less exclusive, not unlike HPV-induced pharynx cancer. Similar to RRP, the angiogenic papillary disease morphology is well suited for voice-preserving angiolytic KTP laser treatment. Given the resemblance of some glottic cancers to RRP, great care should be taken when using cidofovir for papillary glottic neoplasms., (© The Author(s) 2015.)

We conducted a case-control study to investigate the effect of diet on laryngeal carcinogenesis. Our study population was made up of 140 participants-70 patients with laryngeal cancer (LC) and 70 controls with a non-neoplastic condition that was unrelated to diet, smoking, or alcohol. A food-frequency questionnaire determined the mean consumption of 113 different items during the 3 years prior to symptom onset. Total energy intake and cooking mode were also noted. The relative risk, odds ratio (OR), and 95% confidence interval (CI) were estimated by multiple logistic regression analysis. We found that the total energy intake was significantly higher in the LC group (p < 0.001), and that the difference remained statistically significant after logistic regression analysis (p < 0.001; OR: 118.70). Notably, meat consumption was higher in the LC group (p < 0.001), and the difference remained significant after logistic regression analysis (p = 0.029; OR: 1.16). LC patients also consumed significantly more fried food (p = 0.036); this difference also remained significant in the logistic regression model (p = 0.026; OR: 5.45). The LC group also consumed significantly more seafood (p = 0.012); the difference persisted after logistic regression analysis (p = 0.009; OR: 2.48), with the consumption of shrimp proving detrimental (p = 0.049; OR: 2.18). Finally, the intake of zinc was significantly higher in the LC group before and after logistic regression analysis (p = 0.034 and p = 0.011; OR: 30.15, respectively). Cereal consumption (including pastas) was also higher among the LC patients (p = 0.043), with logistic regression analysis showing that their negative effect was possibly associated with the sauces and dressings that traditionally accompany pasta dishes (p = 0.006; OR: 4.78). Conversely, a higher consumption of dairy products was found in controls (p < 0.05); logistic regression analysis showed that calcium appeared to be protective at the micronutrient level (p < 0.001; OR: 0.27). We found no difference in the overall consumption of fruits and vegetables between the LC patients and controls; however, the LC patients did have a greater consumption of cooked tomatoes and cooked root vegetables (p = 0.039 for both), and the controls had more consumption of leeks (p = 0.042) and, among controls younger than 65 years, cooked beans (p = 0.037). Lemon (p = 0.037), squeezed fruit juice (p = 0.032), and watermelon (p = 0.018) were also more frequently consumed by the controls. Other differences at the micronutrient level included greater consumption by the LC patients of retinol (p = 0.044), polyunsaturated fats (p = 0.041), and linoleic acid (p = 0.008); LC patients younger than 65 years also had greater intake of riboflavin (p = 0.045). We conclude that the differences in dietary consumption patterns between LC patients and controls indicate a possible role for lifestyle modifications involving nutritional factors as a means of decreasing the risk of laryngeal cancer.

Background: Head and neck cancer emergency presentations are uncommon but persistent. However, there is little published literature on this aspect of cancer and patient demographics. This study aimed to assess the incidence, patient profile, tumour site and stage of emergency cancer presentations in our region., Method: Retrospective review of regional cancer database over a five-year period., Results: Emergency presentations accounted for 7 per cent of all cases. There was no difference in patient age and risk factors between the emergency and non-emergency presentations. The emergency presentation group showed a greater proportion of female patients compared to the non-emergency presentation group (30 vs 15 per cent). In all emergency presentations, the cancer was at advanced stages. Oropharyngeal cancer was the commonest emergency presentation of cancer, but the third commonest in the non-emergency group., Conclusion: Emergency presentations are increasing annually. Female patients and oropharyngeal cancer showed greater representation compared to male patients and laryngeal cancer.

Background: Recent studies have reported a human papillomavirus (HPV) prevalence of 20% to 30% in laryngeal squamous cell carcinoma (LSCC), although clinical data on HPV involvement remain largely inconsistent, ascribed by some to differences in HPV detection methods or in geographic origin of the studies., Objective: To perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in LSCC., Methods: Literature was searched from January 1964 until March 2015. The effect size was calculated as event rates (95% confidence interval [CI]), with homogeneity testing using Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size. Potential publication bias was estimated using funnel plot symmetry., Results: One hundred seventy nine studies were eligible, comprising a sample size of 7,347 LSCCs from different geographic regions. Altogether, 1,830 (25%) cases tested HPV-positive considering all methods, with effect size of 0.269 (95% CI: 0.242 to 0.297; random-effects model). In meta-analysis stratified by the 1) HPV detection technique and 2) geographic study origin, the between-study heterogeneity was significant only for geographic origin (P = .0001). In meta-regression, the HPV detection method (P = .876) or geographic origin (P = .234) were not significant study-level covariates. Some evidence for publication bias was found only for studies from North America and those using non-polymerase chain reaction methods, with a marginal effect on adjusted point estimates for both., Conclusions: Variability in HPV detection rates in LSCC is explained by geographic origin of study but not by HPV detection method. However, they were not significant study-level covariates in formal meta-regression., Level of Evidence: NA., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

To assess the prognostic factors for local control in patients with early glottic cancer, we retrospectively analyzed the data of 130 consecutive patients who were treated by definitive radiation therapy (RT) or concurrent chemoradiotherapy (CRT) for early glottic squamous cell carcinoma (UICC sixth edition T1N0M0 and T2N0M0) at Kanagawa cancer center between 1999 and 2011. There were 63 patients with T1 cancer and 67 patients with T2 cancer. Twenty-one patients with T2 tumors were treated by chemoradiotherapy (CRT). The median follow-up period was 73 months (range, 22-165 months). The 5-year local control (LC) rate in all patients was 81 %. The 5-year LC rates in the patients with T1 and T2 cancer were 89 and 74 %, respectively. Univariate analysis showed that a higher T stage (T2) (p = 0.0301), anterior commissure involvement (p < 0.000001), and habitual drinking (p = 0.054) were correlated with decreased local control rate. Multivariate analysis identified only anterior commissure involvement as a significant prognostic factor for local control (LC rate 91 vs. 51 %, risk ratio 5.3, 95 % CI 2.3-12, p < 0.001). In the patients with T2 cancer, there was no statistically significant difference in the LC rate between patients who received RT alone and those who received CRT (RT alone 76 % vs. CRT 67 %; p = 0.832). The findings of this study suggest that anterior commissure involvement is a significant factor influencing the prospect of local control. CRT was not found to be effective for T2 patients in this study.

Objectives: The indications for neck dissection concurrent with salvage laryngectomy in the clinically N0 setting remain unclear. Our goals were to determine the prevalence of occult nodal disease, analyze nodal disease distribution patterns, and identify predictors of occult nodal disease in a salvage laryngectomy cohort., Study Design: Case series with planned data collection., Setting: Tertiary academic center., Subjects: Patients with persistent or recurrent laryngeal squamous cell carcinoma (LSCC) after radiation/chemoradiation failure undergoing salvage laryngectomy with neck dissection., Methods: We analyzed a single-institution retrospective case series of patients between 1997 and 2014 and identified those who had clinically N0 (cN0) necks (n = 203). Clinical and pathologic data, including nodal prevalence and distribution, were collected and statistical analyses performed., Results: Overall, cN0 necks had histologically positive occult nodes in 17% (n = 35) of cases. Univariate predictors of occult nodal positivity included recurrent T4 stage (34% T4 vs 12% non-T4; P = .0003) and supraglottic subsite (28% supraglottic vs 10% nonsupraglottic; P = .0006). Histologically positive nodes associated with supraglottic primaries were most frequently positive in ipsilateral levels II and III (17% and 16%). Positive nodes for glottic LSCC were most frequently positive in the ipsilateral and contralateral paratracheal nodes (11% and 9%)., Conclusion: Histologically positive occult nodes are identified in 17% of cN0 patients undergoing salvage laryngectomy with neck dissection. Occult nodal disease varies in frequency and distribution based on tumor subsite. Predictors of high (>20%) occult nodal positivity include T4 tumors and supraglottic subsite. In glottic LSCC, the most frequent sites of occult nodal disease are the paratracheal nodal basins., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Purpose: To describe the pattern of failure in a national consecutive cohort of patients with glottic squamous cell carcinomas (SCC) treated with primary radiotherapy (RT) with curative intent over a 41-year period., Materials and Methods: All patients undergoing curative treatment for a glottic SCC diagnosed in Denmark between 1971 and 2011 were included and followed from the first contact with the oncology center to death or February 15, 2015., Results: 5001 patients were identified of whom 98% had primary RT. The median follow-up was 9.1 years/5.7 years (patients alive/patients who died). Ten patients were lost to follow-up. In total 1511 failures were observed; of these 93%, 11% and 5% included T site, N site, and M site, respectively. For patients diagnosed in the 70s and the 00s, respectively, the five-year incidences were: local failure (32% vs 19%), loco-regional failure (34% vs 21%), laryngectomy (26% vs 10%), laryngectomy-free survival (48% vs 62%), disease-free survival (62% vs 68%), and overall survival (62% vs 68%). The five-year incidence of ultimate failure (13-16%) remained statistically unchanged., Conclusion: From the 70s to the 00s a continually improving primary disease-control was observed with a concurrent decrease in the incidence of laryngectomy. The survival rate was significantly higher in the 00s compared to the previous three decades., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Subglottic squamous cell carcinoma (SCCa) is a rare malignancy representing <5% of all laryngeal cancers. Patients often present with late-stage disease, and survival outcomes are reportedly worse than those for SCCa in other regions of the larynx., Study Design: Analysis of a population-based tumor registry., Setting: Academic medical center., Subjects and Methods: The US National Cancer Institute's Surveillance, Epidemiology, and End Results database was queried for cases of subglottic SCCa from 1973 to 2011 (889 cases). Resulting data were analyzed, including patient demographics, therapeutic measures, and survival outcomes., Results: Subglottic SCCa most frequently occurred in the fifth to seventh decade of life, with a mean age at diagnosis of 65.7 ± 11.3 years. There was a strong male predilection, with a male:female ratio of 3.83:1. Most patients were stage III and IV (64.4%) per the American Joint Committee on Cancer. The most common treatment modality was a combination of radiotherapy and surgery (38.8%), followed by radiotherapy alone (33.9%), and surgery alone (17.0%). Overall 5-year disease-specific survival rate was 53.7%. When stratified by treatment modality, 5-year disease-specific survival was 62.4% for surgery alone, 56.7% for radiotherapy alone, and 55.1% for surgery with adjuvant radiotherapy (P = .3892)., Conclusion: This study represents the largest cohort of subglottic SCCa. It shows a strong predilection for men in the US population. Surgery with adjuvant radiotherapy was the most commonly employed treatment modality. No statistically significant differences were observed in 5-year DSS by treatment modality., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Total laryngectomy (TL) is often still recommended as a salvage approach for recurrent laryngeal squamous cell carcinoma (LSCC). Considering LSCC recurrences after the failure of primary transoral laser microsurgery (TLM), open partial horizontal laryngectomy (OPHL) could be a valid alternative to TL in selected patients. The aim of the present study was to analyze retrospectively the oncological outcome of a consecutive series of 17 patients treated at the Otolaryngology Unit of Vittorio Veneto Hospital (Italy) with OPHL after primary TLM had failed. Nine patients (53 %) had no further recurrences after salvage OPHL. Eight patients had a second recurrence of LSCC after OPHL, and five of them were cured by further salvage treatment, while the other three died of their disease. We found an overall and disease-specific survival both of 82 % and a loco-regional control rate and an ultimate organ preservation rate of 82 and 70 %, respectively. Patients who underwent two-stage bilateral cordectomy for primary glottic carcinoma showed a trend towards a higher rate of second recurrences, a lower ultimate organ preservation rate and a shorter disease-free survival after salvage OPHL. Further studies on larger cohorts of patients are needed to identify potential clinical and/or pathological prognostic parameters capable of pinpointing patients at higher risk of second recurrences after salvage OPHL in cases where TLM has failed. A salvage TL might be reasonably proposed as a first salvage choice in such cases.