bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of race and gender disparities in mortality trends from patients diagnosed with nasopharyngeal, oropharyngeal and hypopharyngeal cancer from 2000 to 2014.
Authors: Badin Kristine , Nayak Kapoor Asha , Guddati Achuta Kumar 
Published: May 2019

e17533 Background: Squamous cell carcinoma of the nasopharynx, oropharynx and hypopharynx constitutes a majority of head neck malignancies. The incidence-based mortality across different races has been noted to be divergent. This study analyzes the trend in incidence-based mortality from the years 2000 to 2014 amongst both the genders in Caucasian/White and African American/Black patients. Methods: The Surveillance, Epidemiology, and End Results (SEER) Database was queried to conduct a nation-wide analysis for the years 2000 to 2014. Incidence-based mortality for all stages of nasopharyngeal, oropharyngeal and hypopharyngeal cancer was queried and the results were grouped by race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander) and gender. All stages and ages were included in the analysis. T-test was used to determine statistically significance difference between various subgroups. Linearized trend lines were used to visualize the mortality trends of all sub groups. Results: Incidence-based mortality rates (per 1000) for nasopharyngeal, oropharyngeal and hypopharyngeal cancer all races and both the genders is shown in the table below. The male to female gender disparity in mortality is~ 1:3 in patients with nasopharynx across all races and becomes worse to ~1:4 and ~1:5 for patients with oropharyngeal and hypopharyngeal cancers respectively. Notably the highest incidence based mortality for nasopharyngeal cancers is seen in Asian/pacific Islander males and a similar peak is noted for hypopharyngeal cancers in African American/Black males. Conclusions: A significant gender disparity exists in all there pharyngeal cancers across all races. It is unclear if female gender is protective but further study is warranted in a stage- specific and age-specific manner to better understand this disparity.[Table: see text]
Genome-wide study of salivary microRNAs as potential noninvasive biomarkers for detection of nasopharyngeal carcinoma.
Authors: Wu Lirong , He Xia 
Published: May 2019

e17535 Background: Since recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis, a new field has been opened for circulating miRNAs as potential biomarkers in cancers. In this pilot study, we evaluated to our knowledge for the first time whether salivary miRNAs might be applicable as innovative biomarkers for Nasopharyngeal carcinoma (NPC) detection. Methods: By high throughput label-free microarray contained 2025 human miRNA probes, 12 down-regulated miRNAs from saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls were selected. Then, their target genes enriched by gene ontology and pathway were used to construct a regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. Results: Advanced bioinformatics analysis was conducted to understand the most significant hub gene is TP53 that probably regulated by the 12 dysregulated miRNAs. The ROC including the 12 miRNAs as well as the 6 significant deregulated miRNAs separated NPC patients from healthy controls with a very high (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%) and high accuracy (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%), respectively. Conclusions: Differentially expressed miRNAs might play critical roles in NPC by regulating their target genes, and may have the potential to become diagnostic biomarkers.
Comparison of the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging for oropharyngeal squamous cell carcinomas (OPSCC): A Surveillance, Epidemiology and End Results Program (SEER) database analysis.
Authors: Trivedi Sumita , Song Haocan , Liu Yuan , Steuer Conor Ernst , Stokes William , Kaka Azeem , Patel Mihir , Chen Zhuo Georgia , Shin Dong Moon , Aiken Ashley , Beitler Jonathan Jay , Saba Nabil F. 
Published: May 2019

e17538 Background: The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, incorporates significant changes to the prior seventh edition. The changes reflect the improved understanding of tumor biology, prognostic factors and molecular markers that effect outcomes in Head and Neck cancers. A key update restages OPSCC by human papilloma virus (HPV) positive and negative cancers as data demonstrated that these tumors have significantly different biology and outcomes. Methods: Using SEER data from 2004 – 2014, we identified male patients with squamous cell carcinomas of the tonsil, base of tongue and soft palate aged between 21 and 64 years old (those clinical characterizes were considered as surrogate markers for HPV positive status). We classified them by the AJCC 8th edition staging for HPV positive OPSCC and by AJCC 7th edition staging. The prediction performance by two staging editions were compared regarding overall survival (OS) and Disease free survival (DFS). Kaplan-Meier method and Cox proportional hazard model were applied, and the discrimination performance was measured by the concordance statistics (C-statistics). Results: A total of 8202 eligible patients were included in the analysis with a median follow up period of 51 months. 7415 (90.4%) patients had previously received radiation and 7038 (85.8%) patients had previously received chemotherapy. The median age of patients was 56 years. Distribution of stage I disease increased from 2% to 19.6% in AJCC 8th edition. 10-year overall survival (OS) for AJCC 8th stages I (74%), II (78%), III (55%) and IV (32%). Using Stage I as reference, the hazard ratio for stage II, III, and IV is 0.98 (95%CI: 0.87-1.09), 2.29 (95%CI: 2.04-2.57), and 5.88 (95%CI: 4.96-6.98). Similar results were noted for ten year disease free survival. The C-statistics measured overall discrimination for 8th edition is 0.68 and 0.63 for the 7th edition (P < 0.001). Conclusions: Based on this SEER analysis, the overall performance of discrimination improved from AJCC 7th to 8th edition; but in this study population, AJCC 8th edition does not distinguish stage I and II sufficiently as expected as it does for stages III and IV disease. Limitations of the SEER database include the surrogate for P16 status and under reported and incomplete data.
Translating transcriptome to immunophenotype in head and neck squamous cell carcinoma (HNSCC) to identify pathways promoting T-cell infiltration.
Authors: Rampias Theodoros , Kontos Christos K. , Polyzos Alexandros , Giotakis Aris , Giotakis Evangelos , Scorilas Andreas , Kirodimos Euthymios , Foukas Periklis , Psyrri Amanda 
Published: May 2019

e17542 Background: We sought to analyze the transcriptional landscape of HNSCC in an attempt to identify tumor-intrinsic oncogenic pathways that appear to mediate T-cell infiltration of tumor tissue. In this direction, we employ a methodology that integrates histopathology data of the tumor microenvironment with its corresponding transcriptome. Methods: 32 frozen HNSCCs were subjected to RNA-seq and corresponding FFPE were scored for plasma cells, tertiary lymphoid structures and CD8a+ TILs (center, invasive margin). RNA-seq data were analyzed to identify differentially expressed genes (DEGs) between tumors scored by immunohistochemistry (IHC) as CD8a high and CD8a low. Gene ontology analysis (GO) was performed based on DEGs > 1.5 fold expression change between CD8a high and CD8a low groups. Candidate genes were investigated by hierarchical clustering in TCGA RNA-seq data and further validated by IHC and quantitative RT-PCR in our cohort. Results: 32 HNSCCs were either scored as CD8a high or CD8a low based on IHC detection of CD8a+ cells in invasive margin of tumors. Comparative analysis of mRNA expression data between CD8a high and CD8a low groups in our cohort revealed that Muc1/16 overexpression and glycosylation was highly enriched in T cell infiltrated group of tumors. This finding was further validated using antibodies that detect glycosylated epitopes for both mucins. Analysis of TCGA RNA-seq data indicated that Muc1/16 overexpressing tumors share signatures of early keratinocyte differentiation and stem cell identity and co-express high levels of enzymes that promote Muc1/16 glycosylation. Interestingly, loss of CDH1 and acquisition of epithelial mesenchymal transition (EMT) markers in the cluster of Muc1/16 overexpressing tumors is strongly correlated with elevated CD8a, IDO1, CD274 and CXCL10 mRNA levels (P < 0.0001). Conclusions: Muc1/16 overexpressing tumors represent a very immunogenic HNSCC cluster. Previous studies have shown that mucins 1 and 16 in cancer cells expose glycosylated-specific epitopes that are recognized by T cells as cancer antigens. To this end, MUC1/16 expression may serve as predictive biomarkers for response to immunotherapy and MUC-targeted immunotherapy may function as an attractive partner to checkpoint inhibitors in HNSCC.
TREM-1 expression in HPV-related oropharyngeal squamous cell carcinoma.
Authors: Airoldi Mario , Raimondo Luca , Azzimonti Barbara , Chiusa Luigi , Pecorari Giancarlo , Cappello Paola , Cena Tiziana , Valente Guido 
Published: May 2019

e17545 Background: Immunotherapy in head and neck squamous cell carcinoma (SCC) is a hot topic and PD1/PDL-1 checkpoint blockade is a promising approach even if there is a lack of robust progno-stic/predictive biomarkers and treatment benefits in overall survival are variable. Triggering Receptor Expressed on Myeloid cell 1 (TREM-1) reverses the M2-polarizing effect of hypoxia imparting a M1-skewed pro-inflammatory phenotype to macrophages that controls tumour growth. Aim of this study is to evaluate the prognostic role of TREM-1 in oropharyngeal (OP) SCC. Methods: In 25 patients with stage III-IV HPV+ OPSCC we evaluated, with immunohistochemistry, in surgical specimens the following immunologic parameters in intratumoral (IT) and peritumoral (PT) environment: PD1-PDL-1 (1+ = < 20% positive cells (pc); 2+ = 21-50% pc; 3+ = > 50% pc) CD4, CD8, FOXP3 (1+ = < 10% pc; 2+ = 10-20% pc ; 3+ = > 20% pc) IL22 (1+ = 1-33% pc, 2+ = 34-67% pc, 3+ = > 67% pc) and TREM ( 1+ = 1-50% pc, 2+ = > 50% pc). The McNemar test was used to assess differences between IT and PT environment. Results: CD4 IT 0/1+ = 12% 2+/3+ = 88% PT 0/1+ = 6% 2+/3+ = 94% FOXP3 IT 0/1+ = 88% 2+/3+ = 12% PT 0/1+ = 65% 2+/3+ = 35% CD8 IT 0/1+ = 12% 2+/3+ = 88% PT 0/1+ = 48% 2+/3+ = 52% PD1 IT 0/1+ = 100% 2+/3+ = 0% PT 0/1+ = 100% 2+/3+ = 0% PDL1 IT 0/1+ = 53% 2+/3+ = 47% PT 0/1+ = 6% 2+/3+ = 94% IL22 IT 0/1+ = 59% 2+/3+ = 41% PT 0/1+ = 29% 2+/3+ = 71% TREM-1 IT 0/1+ = 94% 2 + = 6% PT 0/1+ = 82%* 2+ = 18% * 1+ = 64% Statistical analysis showed a concordant expression of CD4, CD8 and PDL-1 both in IT and PT while TREM-1 was more expressed in PT (p = .001) and PD-1 in IT (p = 0.12).There was no correlation between TREM-1 pc and CD68 and CD35 pc. Tumours with low PT TREM-1 positivity have a lowest risk of relapse (p = .01). Conclusions: HPV+ OPSCC is promoted by inflammatory infiltrate anergy. TREM-1 PT positivity has unfavourable impact on relapse.
Associations between pretreatment body mass index and presence of post-treatment nutrition impact symptoms in head and neck cancer survivors.
Authors: Douglas Katherine G. , Crowder Sylvia L. , Rozek Laura S. , Wolf Gregory T. , Arthur Anna 
Published: May 2019

e17547 Background: The objective of this study was to determine if pre-treatment body mass index (BMI) is associated with the presence of self-reported, nutrition impact symptoms (NIS) 1-year post-treatment in head and neck cancer (HNC) survivors. We hypothesize that higher pre-treatment BMI may be associated with fewer reported NIS post treatment. Methods: This was a longitudinal study of 430 HNC survivors recruited from the University of Michigan Head and Neck Specialized Program of Research Excellence (HN-SPORE) study. Participants completed a pre-treatment health questionnaire which included self-reported height and weight. NIS were assessed at 1-year post-treatment using a Likert scale ranging from 1 (not at all) vs 5 (extremely) bothered by symptoms. Eight individual NIS were assessed (trismus, xerostomia, bothered chewing, dysphagia liquids, dysphagia solids, taste changes, mucositis, and shoulder or neck pain). Individual symptoms were summed to create a symptom summary score. Self-reported pre-treatment height and weight were used to calculate BMI in kg/m2. BMI was categorized as 1) underweight, 2) normal weight, 3) overweight and 4) obese. Pearson partial correlations between pre-treatment BMI status and individual post-treatment NIS and post-treatment NIS summary score were examined. Covariates included age, sex, tumor site, disease stage, smoking, alcohol consumption, and HPV status. Results: BMI was significantly inversely associated with bothered chewing, dysphagia liquids, dysphagia solids, taste alterations, and shoulder pain (p < 0.05). BMI was also significantly inversely correlated with the overall symptom summary score. Conclusions: Higher pre-treatment BMI may be associated with reduced risk of post-diagnosis symptom burden in HNC survivors. Funding: NIH/NCI P50CA097248; Hatch project 1011487; Carle-Illinois Cancer Scholars for Translational and Applied Research Fellowship.
Prognostic neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in locally advanced oropharyngeal cancer: a retrospective experience of two institutions.
Authors: Espeli Vittoria G. , Martucci Francesco , Richetti Antonella , Pastore Alessia 
Published: May 2019

e17548 Background: the Neutrophil-to-Lymphocytes ratio (NLR) and the Platelet-to-Lymphocytes ratio (PLR) represent potential prognostic markers in different tumor types. The purpose of our study was to investigate the prognostic role of the pretreatment inflammatory markers NLR and PLR in patients with locally advanced squamous cell oropharyngeal cancer (OPSCC) treated with curative concomitant chemoradiotherapy (CRT). Methods: between 2004 and 2016, all patients with OPSCC diagnosed at the University Hospital of Varese and the Oncology Institute of Southern Switzerland were reviewed retrospectively. CRT consisted of Intensity-Modulated Radiation Therapy (IMRT) to a dose of 66-70 Gy concomitant to 3 doses of 3-weekly cisplatin. Pre-treatment NLR and PLR were registered from blood samples obtained within 14 days before treatment. 3-year disease free survival (DFS) was analyzed. Results: ninety-two patients were identified. Median follow-up was 39 months. Median NLR was 3 and median PLR was 153. The 3 year DFS was 82.9%. Univariate analysis showed that HPV status and PLR were statistically significant factors in determining 3-year DFS (p 0.01 and 0.04 respectively). Multivariate analysis showed that only HPV status was a statistically significant factor for 3-year DFS (p 0.009). High NLR and high PLR were correlated with lower DFS: patients with NLR > 4 had a 3-years DFS of 50% versus 75%in the group with NLR ≤ 4(p = 0.04) and patients with PLR > 150 had a 3-years DFS of 65% versus 82% in the group with PLR ≤ 150 (p = 0.04). Conclusions: in our case series, NLR and PLR were significantly associated with clinical outcome. Additional data are necessary to investigate the prognostic value of inflammatory markers and to identify the ideal cut-off of both markers.
Upstaging of head and neck cancers due to extranodal extension: An Indian study.
Authors: Joseph Deepa M. , Raut Sagar , Pasricha Rajesh , Gupta Sweety 
Published: May 2019

e17553 Background: Latest AJCC staging has included extranodal extension (ENE) in nodal staging of head and neck cancers (HNC) in view of its prognostic significance. Presence of clinical ENE makes the disease N3b and the stage grouping will be stage IVB. This retrospective analysis was done with an objective to find out the percentage of patients with HNC getting upstaged because of ENE and their treatment outcome. Methods: A retrospective analysis of all HNC patients registered in our department from January 2018 to January 2019 were done to identify the presence of ENE and their staging. AJCC criteria was used for defining clinical and radiological ENE. The site, subsite, stage and presence of ENE were documented. Results: A total of 562 patients were registered with HNC. Among them 40 patients were identified to have ENE (7.1%). There were 35 males and 5 females. There were 17 cases with ca oropharynx, 13 oral cavity, four hypopharynx, three supraglottis, two glottis, and one maxillary carcinoma. Tumour size varied from 1.5 cm to 8 cm with an average of 4.9cm. Majority of the patient had a T4a disease, with 18 patients in the category. T stage varied from T1 – 1, T2 – 7, T3 – 7, T4b – 6, missing data – 1. 33 patients had clinically documented ENE and six were radiological and one patient had pathological ENE. Nine had skin involvement and the rest (24) had either muscle invasion or soft tissue involvement. Various treatment approaches were tried. Two patients received neoadjuvant chemotherapy (NACT) followed by chemoradiation (CTRT). On treatment at present. One NACT followed by surgery and later CTRT. Developed recurrence. Four patients received palliative chemotherapy, but developed progressive disease (PD), on best supportive care (BSC). Nine patients received palliative radiotherapy, six patients are on treatment and one had PD. Five patients received radical CTRT, 5 on treatment and one had PD. One received palliative RT followed by palliative chemo, but developed PD. 13 patients are on treatment and rest of the patients are either dead, lost to follow up or on BSC. Conclusions: Majority of the patients with ENE had a T4a disease. No special site predilection was identified. Various treatment modalities tried but none of them produced any significant difference in outcome. In conclusion, patients with ENE had a poor prognosis irrespective of the treatment modality selected.
Changes in the proportion of squamous cell carcinoma in head and neck cancer in the United States and Canada, 1995-2015.
Authors: Gaubatz Matthew , Bukatko Aleksandr R , Polednik Katherine M. , Simpson Matthew C , Adjei Boakye Eric , Mohammed Kahee A , Osazuwa-Peters Nosayaba 
Published: May 2019

e17554 Background: There has been a shift in the epidemiologic landscape of head and neck cancer (HNC) with decreasing incidence of tobacco-related and increasing incidence of human papillomavirus (HPV)-related HNC. While it is often reported that ≥ 90% of HNC is considered squamous cell carcinoma (SCC), there is an apparent lack of recent population-based data to support this claim. This study aimed to estimate the current proportion and evaluate change in the proportion of SCC in HNC diagnoses in North America (United States and Canada) from 1995 to 2015. Methods: We queried the North American Association of Central Cancer Registries (NAACCR) database for HNC cases that were of either squamous (SQ) (ICD-0-3: 8050-8089) or squamous plus unspecified epithelial (SQE) (ICD-0-3:8010-8089) origin in the United States and Canada ( n = 1,054,409). All HNC included in the analysis were microscopically confirmed, malignant head and neck primary tumor sites of the oral cavity, nasopharynx, hypopharynx, oropharynx, nasal cavity, and larynx. Sub-analyses were conducted across more extensive cohort restriction combinations (country specific, registry specific, and primary sequence of cancer). Results: The overall proportion of SCC in HNC in North America from 1995-2015 was 81.7% (95% CI: 81.7 – 81.8) for SQ and 84.9% (95% CI: 84.8 – 85.0) for SQE. The proportion of SCC in HNC peaked in 2015 with 83.3% (95% CI: 83.0 – 83.6) for SQ and 85.9% (95% CI: 85.6 – 86.2) for SQE; and was lowest in 2005 with 80.7% (95% CI: 80.4 – 81.1) for SQ and 84.3% (95% CI: 83.9 – 84.6) for SQE. In the time period of this study (1995 – 2015), there were no years for which SQ or SQE made up 90% or more of HNC for any of the HNC cohorts. Conclusions: The changing landscape of HNC risk factors in the United States and Canada warrants re-evaluation and update of HNC epidemiological literature with regards to the proportion of SCC in HNC.
Cumulative odds of increased comorbid score in head and neck cancer.
Authors: Polednik Katherine M. , Bukatko Aleksandr R , Gaubatz Matthew , Simpson Matthew C , Adjei Boakye Eric , Mohammed Kahee A , Osazuwa-Peters Nosayaba 
Published: May 2019

e17555 Background: Survival of head and neck cancer is impacted by known clinical factors, including anatomic subsite, stage of presentation, and treatment modality. An important clinical factor less explored is comorbidity burden. While it is known that a greater comorbidity burden is prognostic for poorer outcomes, it is unclear how the odds of presenting with increased comorbidity score is associated with head and neck cancer anatomic subsite. This study aimed at estimating the cumulative odds of increased comorbidity in head and neck cancer based on anatomic subsites. Methods: Data queried from National Cancer Database (2004-2015). Study sample (N = 328,504) consisted of Stage I-IV, Head and neck Squamous Cell Carcinoma (HNSCC) patients, with no missing demographic variables (age, sex, race, insurance status, local income, local population density). Multivariable cumulative logit model was used to estimate outcome of interest: odds of higher Charlson-Deyo comorbid condition score(CDCC) at HNSCC diagnosis. Results: Compared to patients diagnosed with oropharyngeal cancer (mostly HPV-related HNSCC), patients diagnosed with more tobacco-related HNSCC, such as laryngeal cancer (aOR: 1.69, 95% CI: 1.65-1.73), hypopharyngeal cancer (aOR: 1.33, 95% CI: 1.28-1.38), oral cavity (aOR: 1.26, 95% CI: 1.23-1.29), and sinonasal cancer (aOR: 1.12, 95% CI: 1.06-1.19) had greater odds of presenting with a higher CDCC. Patients with nasopharyngeal cancer did not statistically differ from oropharyngeal patients in odds of higher CDCC presentation. Conclusions: Patients diagnosed with cancers of larynx, hypopharynx and oral cavity (typically associated with tobacco and alcohol use) present with greater comorbid burden compared to patients diagnosed with oropharyngeal cancer (typically associated with HPV). It is important that the role of comorbidity burden be recognized in head and neck cancer prognostication.