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Comorbidities have shown to highly influence the outcome and risk of death of head and neck cancer patients. The purpose of this study was to examine the comorbidities among oral cavity squamous cell carcinoma (OSCC) patients, and to investigate the impact of comorbidities on overall survival (OS) and recurrence free survival (RFS). Patients diagnosed with OSCC in Eastern Denmark in the period 2000–2014 and treated with curative intend were included. Patients data were linked to the Danish National Patients Register to identify comorbidities based on the Charlson Comorbidity Index (CCI) at the time of diagnosis and five years after diagnosis. Each patient was age-and sex-matched in a 1:10 ratio with an age and sex matched reference group. A total of 1,183 patients and 11,830 controls were included. Overall this study found comorbidities to be more common among OSCC compared to the reference group both at the time of diagnosis and five years after. The 5-year OS among patients with a CCI score of zero, one, two, and three or above was 60%, 44%, 41%, and 40%, respectively. Similarly, the multivariate cox-regression analysis showed that patients with increasing CCI score also had an increasing risk of death compared to patients with no comorbidities. OSCC patients had significantly higher comorbidity burden at diagnosis and risk of developing additional comorbidities after diagnosis compared to the reference population. Survival outcomes decreased significantly with higher CCI. [ABSTRACT FROM AUTHOR]

Objectives: Comorbid conditions impact outcome for patients treated for oropharyngeal squamous cell carcinoma (OPSCC) and serve as competing risk factors for death. The purpose of this study was to examine differences in comorbidities in patients with OPSCC and known HPV-DNA.Material and Methods: We included patients diagnosed with OPSCC in Eastern Denmark in 2000-2014. Patients were linked to the Danish National Patient Register to identify comorbidities based on the Charlson Comorbidity Index (CCI) at time of diagnosis and following cancer treatment. Patients were age-and sex-matched in a 1:10 ratio with a reference group and stratified according to HPV-status.Results: In total 1,499 patients (55.0% HPV+) and 14,990 controls were included. Significantly more HPV+ patients had no comorbidities compared to HPV- patients at time of diagnosis (RR: 1.5 (1.3;1.6), n = HPV+: 522, HPV-: 302) and following treatment (RR 1.5 (1.4;1.6), n = HPV+: 342, HPV-: 142). Most prevalent comorbidity was malignancy not including OPSCCs. HPV+ patients had an increased risk of having AIDS before their OPSCC diagnosis compared to the reference population (OR: 4.8 (1.8;12.9)). HPV- patients had increased risk of multiple comorbidities including cerebrovascular disease (OR: 1.9 (1.4;2.5)), peripheral vascular disease (OR: 1.7 (1.9;3.7)), dementia (OR: 2.9 (1.4;5.8)), ulcer disease (OR: 2.6 (1.9;3.5)), liver disease, mild (OR: 9.5 (7.0;13.0)) and severe (OR: 13.9 (5.8;22.8)).Conclusion: This study showed that HPV- patients had more comorbidities than HPV+ patients at the diagnosis time and following treatment. Irrespective of HPV-status, OPSCC patients had a significant increased risk of (secondary) malignancy compared to the reference population. [ABSTRACT FROM AUTHOR]

aim was to establish a large comprehensive database of patients with oral cavity squamous cell carcinoma (OSCC) to enable surveillance and research of the disease. Methods: All patients diagnosed and/or treated for OSCC at Rigshospitalet, University of Copenhagen, Denmark in the period 2000–2014 were included. Rigshospitalet is a tertiary treatment center and covers the Eastern Denmark region, comprising nearly half of the approximately 5.8 million inhabitants of Denmark. Data on numerous variables regarding general information of the patients at diagnosis, their primary cancer, recurrence, treatment, prior cancers, and secondary cancers were collected from the Danish Pathology Register and by evaluation of medical charts. Results: One thousand three hundred and ninety-nine OSCC patients were included in the database (62% males). The median age at diagnosis was 63 years (range: 23–99 years). The most common anatomical location was the floor of mouth (38%). Among patients with known stage, 70.0% were diagnosed in T-stage 1 or 2 and 64.9% were diagnosed in N-stage 0. Most patients were treated with primary surgery (81.7% among patients with known treatment), of these 44% received adjuvant radiotherapy after surgery. The overall age-standardized incidence of OSCC per 100,000 increased from 2.15 in 2000 to 3.04 in 2014, with a significant annual percent change of 3.2%. Conclusion: We have established a consecutive, population-based database of 1,399 OSCC patients. This creates a basis for multiple studies that will elaborate our understanding of OSCC, and hopefully improve diagnosis, treatment, and rehabilitation of OSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Currently, data is sparse on the pattern and timing of recurrence. This long-term study concerning both HPV- and p16-status aimed to report predictive factors, pattern, timing of loco-regional recurrence (LRR) and distant recurrence (DR), and survival following recurrence in patients diagnosed with OPSCC.Material and Methods: We included patients diagnosed with OPSCC from 2000 to 2014 in Eastern Denmark, who were treated with curative intent. Tumors were defined as HPV-positive when they were both HPV-DNA and p16-positive. Time-to-failure and -death were estimated by the Kaplan-Meier method. Cox proportional hazards models were used to evaluate predictors of failure.Results: The cohort consisted of 1244 consecutive patients with OPSCC of which 288 patients (23%) experienced recurrence. Of these patients, the majority (n = 197/1244; 16%) experienced LRR and the remaining (n = 91/1244; 7%) DR. Significantly more HPV-negative patients experienced recurrence (n = 170/486; 35%) compared to HPV-positive patient (n = 112/726; 15%). DR occurred for both groups predominantly to the lung (n = 63/91; 69.2%) followed by the liver and bone. Factors influencing risk of LRR included gender, T-classification, and HPV-status. The same variables influenced risk of DR in addition to the UICC-8 classification, N-classification, pack years of smoking, and performance status. HPV-status was the strongest risk factor for LRR and DR.Conclusion: LRR and DR occur significantly less often in HPV-positive patients compared with HPV-negative patients. HPV-status is an independent and strong predictor of recurrence. DR most commonly occurs to the lungs, irrespective of HPV-status. [ABSTRACT FROM AUTHOR]

Background: Salivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. This trial assessed the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia.Patient and Methods: This randomized, placebo-controlled phase 1/2 trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and after the intervention. All assessments were performed one month prior (baseline) and one and four months following ASC or placebo administration.Results: No adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; P = .048) and four months (50%; P = .003), but not in the placebo-arm (P = .6 and P = .8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, P = .035) and difficulties in eating solid foods (-2%, P = .008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (P = .04 and P = .02, respectively). MRIs showed no significant differences between groups in gland size or intensity (P < .05).Conclusions: ASC therapy for radiation-induced hypofunction and xerostomia was safe and significantly improved salivary gland functions and patient-reported outcomes. These results should encourage further exploratory and confirmatory trials. [ABSTRACT FROM AUTHOR]

Background: The genetic profile for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) remains largely unknown. The purpose of this study was to sequence tissue material from a large cohort of locoregionally-advanced HPV+ OPSCCs.Methods: We performed targeted deep sequencing of 395 cancer-associated genes in 114 matched tumor/normal loco-regionally advanced HPV+ OPSCCs. Mutations and copy number aberrations were determined.Results: We identified a total of 3459 mutations with an average of 10 mutations per megabase and a median of 28 variants per sample. The most frequently mutated genes were KALRN (28%), SPTBN1 (32%), KMT2A (31%), ZNRF3 (9%), BNC2 (12%), NOTCH2 (25%), FGFR2 (12%), SMAD2 (6%), and AR (13%). Our findings were dominated by COSMIC signature 5 and 12, represented in other head and neck cancers and in hepatocellular carcinomas, respectively.Conclusions: We have identified multiple genetic aberrations in HPV+ OPSCCs, and the COSMIC signature 12 as most prevalent. The mutations harbour both therapeutic and prognostic potential. [ABSTRACT FROM AUTHOR]

Background: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries.Methods: Consecutive OPSCC patients treated in Denmark, 2000-2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance.Results: In the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration.Conclusions: Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org . [ABSTRACT FROM AUTHOR]

Background: Information on the incidence, indications and morbidity of pediatric tracheotomy from a nationwide setting is sparse.Methods: From the nationwide Danish National Patient Registry, we identified all cases: 0–15-year-old children registered with a first-time tracheotomy from 1979 to 2014. We extracted the date of surgery, admission, discharge, age, gender, hospital, department, hospitalization length, hospital contacts, and diagnosis-code related to the surgery. We estimated age-adjusted incidence rates (AAIR) and annual (APC) and average annual percentage change (AAPC) of tracheotomy incidence.Results: A total of 510 children (328 boys, 63%) underwent tracheotomy. The median age at surgery was 8 years. The AAIR was 1.4/100,000 person-years (range 1.0–1.8) from 1980 to 2014. During 1979–2014, the AAPC decreased − 0.9% (95% confidential interval – 2.4; 0.8, p < 0.3). From 1979 to 2003 the APC decreased − 4.1% (95% CI − 5.4; − 2.8, p < 0.001) and from 2003 to 2014 the APC increased 6.6% (95% CI 2.0; 11.5, p < 0.001). Infants had the highest incidence (4.0/100,000 years) compared with the 12–15-year-olds (AAIR: 0.4/100,000 years). From 1979 to 2014 the most common indication for tracheotomy among children aged 0–2 years was congenital malformations (n = 48, 30%) and among children aged 3–11 and 12–15 years the most common indication was trauma (respectively n = 67, 36% and n = 85, 52%). During 2006–2014 the most common indications for all ages was neurological impairment (n = 25, 21%) and neoplasms (n = 20, 17%).Conclusions: Pediatric tracheotomy was a rare surgical procedure with decreasing incidence rates from 1980–89 to 1990–99 and increasing incidence rates from 2000–2009 to 2010–2014. Indications and postoperative morbidity have changed adjunct to the treatment of chronic disorders. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal carcinomas (OPCs) constitute a significant and increasing proportion of head and neck carcinomas and are an important global cause of morbidity and mortality. The purpose of this study was to determine trends in incidence and survival in OPC in the Danish population from 1980 to 2014. Methods: This study included all patients registered in the nationwide Danish Cancer Registry over the period 1980-2014. The age-adjusted incidence rates (AAIR) per 100,000, annual percentage change (APC) and average annual percent change (AAPC) were evaluated. Five-year relative survival (RS) was calculated with Cox regression analyses in relation to gender, anatomical location and histology. Results: A total of 6555 patients (69% male) were included, with a median age at diagnosis of 60 years. The AAIR of patients with OPC increased from 0.815 per 100,000 in 1980 to 4.51 per 100,000 in 2014 with an AAPC of 5.3. The 5-year RS increased significantly from 33.1% over the period 1980-1984 to 58.5% (25.4% points) over the period 2010-2014. With no significant difference stratified for gender. Tumors located at the palatine tonsils (n=3333) and salivary gland OPC (n=90) had significantly better survival compared with other sub-locations and histology subtypes. In the APC model the birth cohort effect rate ratio increased until 1925 and then decreased until 1935 from which point it increased in the last cohorts. Conclusions: In this population-based study, we observed a significant increase in the incidence of OPCs and in the RS for OPC. We also identified a profound birth cohort effect on the incidence. [ABSTRACT FROM AUTHOR]

Identifying the causes of death in head and neck cancer patients can optimize follow- up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause- specific mortality in a population- based cohort of patients with OPSCC. Patients who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern Denmark were included in the study. Causes of death were collected through medical files and the Danish National Cause of Death registry. Deaths were grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3) cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative incidence of death and specific causes of death were determined using risk analysis. At follow-up, 723 (47.5%) patients had died. The median time to and cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing secondary screening and prevention strategies for late toxicity and mortality are major goals in managing the treatment of these patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of thyroid cancer (TC) is increasing although explanatory causes are lacking. A link between cancer and inflammation is well documented but unclear for autoimmune thyroid diseases and TC. We aimed to systematically review the association between Hashimoto's thyroiditis (HT) and papillary, follicular, medullary, anaplastic thyroid carcinoma, and thyroid lymphoma (TL). Methods: PubMed, OVID Medline, Google Scholar, and the Cochrane Library were searched from 1955 to 2016. The inclusion criteria were age >18 years, ≥20 cases of HT or TC. We collectively examined the incidence of HT in TC and of TC in HT. Results: We identified 36 studies (64,628 subjects) published between 1955 and 2016 from 13 countries. We found a relative risk (RR) of HT among papillary thyroid cancer (PTC) of 2.36 [95% confidence intervals (CIs) 1.55-3.29, p < 0.001], an RR of PTC among HT of 1.40 (95% CI 1.07-1.85, p = 0.016), and an RR of TL among HT of 9.74 (95% CI 3.93-24.13, p < 0.001). Conclusion: We report an association between HT and PTC and between HT and TL. No association was found between HT and follicular, medullary, or anaplastic thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: A predominant side effect of radiotherapy for head and neck cancer is salivary gland hypofunction and xerostomia leading to debilitating oral disorders and impaired quality of life (QoL). Intraglandular mesenchymal stem cell therapy has shown promising results as a treatment for xerostomia. Methods: This is a randomised, double-blinded, placebo-controlled, parallel-group, prospective, single-centre trial investigating the safety, tolerability, and effectiveness of allogeneic stem cells as a treatment for radiation-induced hyposalivation and xerostomia for previous head and neck cancer patients. We will include a total of 120 patients who previously have been treated with radiotherapy for a head and neck cancer in Denmark. Participants will be randomly assigned using block randomisation to one of two parallel groups in a 1:1 ratio to receive ultrasound-guided injection of allogeneic adipose-derived mesenchymal stem cell (ASC) (n = 60) or placebo (n = 60) into the submandibular glands. Placebo will consist of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% dimethyl sulfoxide (DMSO). The primary endpoint is change in unstimulated whole saliva flow rate. The secondary endpoints are change in stimulated whole saliva flow rate, QoL, and composition of saliva. Further secondary endpoints are safety and immune response (human leukocyte antigen (HLA) response) to the stem cells will be assessed. Patients are evaluated at baseline (before treatment), after 4 months, and after 12 months. All study personnel, except study personnel thawing and preparing the treatment for injection, and participants will be blinded to group assignment. Unblinded study personnel will not participate in the outcome assessment. Discussion: The trials will investigate the efficacy and safety of ASC injection to the submandibular gland as a potential new treatment for post-radiation xerostomia. We hope the results will pave the way for a clinically relevant treatment to ameliorate patients with xerostomia, a severely hampering condition. Trial registration: The study is approved by the Danish Data Protection Agency (protocol number P-2020-1164), the National Ethics Committee protocol number: (Protocol number: 1802872), and the Danish Medical Agency (2018-000348-24). The protocol was registered at the ClinicalTrials.gov database (NCT04776538). [ABSTRACT FROM AUTHOR]

A high number of patients seek health information online, and large language models (LLMs) may produce a rising amount of it. This study evaluates the performance regarding health information provided by ChatGPT, a LLM developed by OpenAI, focusing on its utility as a source for otolaryngology-related patient information. A variety of doctors from a tertiary otorhinolaryngology department used a Likert scale to assess the chatbot's responses in terms of accuracy, relevance, and depth. The responses were also evaluated by ChatGPT. The composite mean of the three categories was 3.41, with the highest performance noted in the relevance category (mean = 3.71) when evaluated by the respondents. The accuracy and depth categories yielded mean scores of 3.51 and 3.00, respectively. All the categories were rated as 5 when evaluated by ChatGPT. Despite its potential in providing relevant and accurate medical information, the chatbot's responses lacked depth and were found to potentially perpetuate biases due to its training on publicly available text. In conclusion, while LLMs show promise in healthcare, further refinement is necessary to enhance response depth and mitigate potential biases. [ABSTRACT FROM AUTHOR]

Salivary gland cancer is a rare disease, and approximately 20% of tumors in the salivary glands are malignant. Reliable biomarkers may have a role in monitoring salivary gland cancer. To review the current literature on the role of biomarkers in liquid biopsies and saliva samples in the monitoring of salivary gland cancer. This study systematically reviewed the literature on studies detecting salivary gland cancer by biomarkers in liquid biopsies and saliva samples by systematically searching PubMed and Embase between 1 January 2013 and 7 March 2023. Five studies covering 64 malignant cases of salivary gland cancer were included, which considered inflammatory biomarkers or markers of genetic material in either blood or saliva. In saliva, there were demonstrated elevations of CA-19-9 in malignant cases, and elevations of miRNA in malignant and benign cases. In blood, there were demonstrated elevations of IL-33 in malignant and benign cases, elevations of ctDNA in malignant cases, and elevations of CTC in malignant cases. The studies indicate that there is potential in the detection method. The studies detecting genetic material by liquid biopsies showed the most promising results. At present, there is still progression to be made before the method can be implemented for diagnostic use. [ABSTRACT FROM AUTHOR]

Background: Salivary hypofunction leads to debilitating oral symptoms and has major complications for overall quality of life. Two of the most frequent causes of xerostomia are radiotherapy in the head and neck and Sjögren's syndrome. Only symptomatic treatment is available today. An increasing number of both preclinical and clinical studies have suggested that mesenchymal stem cell (MSC) transplantation treatment can increase the salivary flow rate and ameliorate symptoms of xerostomia. However, both adipose-derived and bone marrow–derived MSCs are used, although they differ in important ways. The primary objective of this study is an indirect comparison of the change in the unstimulated salivary flow rate after intervention between patients treated with adipose-derived or bone marrow–derived MSCs. Methods: This systematic review and network meta-analysis will search for eligible studies in the MEDLINE, EMBASE, and Cochrane CENTRAL register of Controlled Trials. Eligible studies are as follows: clinical studies including human patients with salivary hypofunction due to either radiotherapy or Sjogren's syndrome who were subsequently treated with either adipose-derived MSCs or bone marrow–derived MSCs. Studies with no control group will be excluded. The search phrase has been peer-reviewed following the PRESS guidelines. The primary outcome is the change in the unstimulated salivary flow rate after treatment with either adipose-derived or bone marrow–derived MSCs. Secondary outcomes are as follows: change in patient reported outcomes, methods of intervention administration, number of injected MSCs, and safety. Data from included studies will be pooled and compared with a fixed-effects or random effects model dependent on signs of heterogeneity, presented with a forest plot, and indirectly compared with a meta-regression in a network meta-analysis. Risk of bias will be assessed with the tools ROBINS-I or RoB-2 depending on type of study. Discussion: Both adipose-derived and bone marrow–derived MSCs are used today for experimental treatment of salivary hypofunction in humans as no direct or indirect comparisons have been made. Therefore, an evaluation of the effect of adipose-derived vs bone marrow–derived MSC treatment is needed to support future decision-making on the type of MSC used in a clinical trial. Systematic review registration: PROSPERO ID CRD42024527183. [ABSTRACT FROM AUTHOR]