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Introduction: The aim of this study was to investigate the genomic changes that occur in the development from dysplasia, cancer and to regional metastases in patients with oral cavity squamous cell carcinoma (OSCC). Material and methods: We included OSCC patients with lymph node metastases at diagnosis, treated with primary surgery at Rigshospitalet, University of Copenhagen in the period 2007-2014. The resected tumor specimens were evaluated by a pathologist, who marked areas of morphologically normal tissue and dysplasia surrounding the cancer, two areas from the cancer tissue, and one area within the lymph node metastases. From these areas a punch biopsy was taken, and DNA from each sample was extracted and sequenced using Illumina's TSO500HTcancer panel. Results: From 51 OSCC patients, 255 samples were included, comprising a wide variety of genomic alterations. Substantial intratumor heterogeneity was found. The most commonly mutated gene was TP53, mutated in 65% of all samples. Only two patients had no TP53 mutation in any samples. We found that morphologically normal appearingmucosa aswell as surrounding dysplasia also containedmalignant mutations, supporting the theory of field cancerization. There was a significant lower average tumor mutational burden (TMB) in the lymph node metastases compared to the primary tumors, supporting the theory of clonal selection. Conclusion: Substantial inter- and intratumor genomic heterogeneity was found. Mutation of TP53 was the most common and was present in all but two patients. Our data strongly supports the theory of clonal selection and the theory of field cancerization. [ABSTRACT FROM AUTHOR]

Denmark, alongside other Scandinavian countries, the United States, Canada, and the United Kingdom, has high prevalence of human papillomavirus (HPV). Our oropharyngeal squamous cell carcinoma (OPSCC) database includes all diagnosed cases in Eastern Denmark during a period of more than two decades. We investigated the incidence, survival, and recurrence of patients with OPSCC with combined p16‐ and HPV testing covering a consecutive 21‐year period. Age‐adjusted incidence rate (AAIR) per 100,000, survival models, and Cox proportional‐hazards model were employed. Two thousand eight hundred thirty‐four patients were included (57.5% HPV positive (HPV+)/p16 positive (p16+), 33.7% HPV negative (HPV‐)/p16 negative (p16−), 4% HPV+/p16−, and 4.8% HPV−/p16+). The AAIR for all patients increased from 1.8 to 5.1 per 100,000 from 2000 to 2020 linked to an increasing AAIR of HPV+/p16+ OPSCCs from 0.9 to 3.5 per 100,000 from 2000 to 2020. The AAIR for the HPV−/p16− OPSCCs decreased from 1.6 to 1.4 from 2017 to 2020. HPV+/p16+ OPSCCs had a higher 5‐year overall survival (OS) of 79.2% compared to the other subgroups (HPV+/p16− OS: 50.4%; HPV−/p16+ OS: 49.4%; HPV−/p16− OS: 35.1%). The AAIR of the total OPSCC group increased from year 2000 to 2020, driven by a rise in the HPV+/p16+ group. A decreasing incidence rate was observed for the HPV−/p16− OPSCCs from 2017 to 2020. The OS for HPV+/p16+ OPSCCs was significantly higher compared to all other HPV/p16 subgroups. Therefore, we recommend testing for combined HPV and p16 status in patients with OPSCC when selecting patients for clinical trials, especially in case of de‐escalating/escalating. [ABSTRACT FROM AUTHOR]

Thyroid cancer (TC) represents a significant health burden globally, with follicular thyroid cancer (FTC) posing diagnostic challenges despite advancements. This pilot study aimed to evaluate the utility of a liquid biopsy with cell-free DNA (cfDNA) in patients with FTC. Blood samples were collected from 13 patients diagnosed with FTC, DNA extraction was performed, and cfDNA was analyzed using the Illumina's TruSight Oncology 500 High-Throughput panel. The results revealed low tumor mutational burden and minimal pathogenic variants in cfDNA, indicating challenges such as low DNA yield and poor material quality despite adequate coverage. Our findings indicate that cfDNA as an add-on diagnostic tool in patients with FTC might not be a useful supplement. [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]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To investigate thresholds for lymph node yield (LNY), lymph node density (LND), and pN in patients with oral squamous cell carcinoma in relation to previous findings in the literature. Study Design: Retrospective register‐based study. Setting: Copenhagen Oral Cavity Squamous Cell Carcinoma database. Methods: Appropriate thresholds for LNY, LND, and pN were determined by areas under the curve and subsequently subjected to multivariate analysis. Five‐year overall survival and 3‐year recurrence‐free survival were determined by Kaplan‐Meier survival curves. Results: In total, 413 patients diagnosed with oral squamous cell carcinoma were included. In the pN0 cohort, no superior/prognostic LNY cutoff values were detected. In the pN+ cohort, areas under the curve determined thresholds of LNY, LND, and pN to be 21 nodes, 5%, and 3 metastases, respectively. The 5‐year overall survival was 52% for patients with LNY ≥21 vs 38% for patients with LNY <21 (hazard ratio [HR], 1.49; 95% CI, 1.05‐2.11; P <.05), 60% for patients with LND ≤5% vs 38% for patients with LND >6% (HR, 1.63; 95% CI, 1.03‐2.57; P <.05), and 43% for patients with pN <3 vs 26% for patients with pN ≥3 (HR, 1.40; 95% CI, 1.04‐2.15; P <.05). Conclusions: Increased nodal yield, decreased LND, and decreasing number of pN were associated with significantly improved survival outcomes. LNY might serve as a prognosticator of survival as well as a surgical quality indicator. LND may have implications as a tool in cancer staging and treatment planning. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is an important risk factor in a subset of head and neck squamous cell carcinomas (HNSCC), but the association with oral cavity squamous cell carcinomas (OCSCC) remains controversial. This study aimed to identify the prevalence of HPV infection in OCSCC. A systematic search on PubMed and EMBASE was performed, including articles assessing the prevalence of HPV-positive (HPV+) OCSCC published from January 2017 to December 2022. OCSCC was considered HPV+ by the detection of HPV DNA, HPV RNA, and/or p16 overexpression in the tumor mass. A meta-analysis was made determining the overall HPV+ OCSCC prevalence. We included 31 studies comprising 5007 patients from 24 countries. The study size ranged from 17 to 940 patients. The HPV+ OCSCC proportion variated widely and ranged from 0% to 37%. Tumors in the tongue were the predominant sublocation for HPV in the oral cavity. The meta-analysis revealed that the overall HPV+ OCSCC prevalence is 6% (95% CI; 3–10%), and only one study found HPV and OCSCC significantly associated. Thus, HPV may not be a necessary or a strong risk factor in OCSCC oncogenesis, and the possibility of a site misclassification of a mobile tongue with the root of the tongue cannot be excluded. [ABSTRACT FROM AUTHOR]

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in the past decades due to carcinogenic HPV infection. As this patient group suffers from considerable mortality and treatment morbidity it is important to improve prognostic strategies in OPSCC. Inflammation plays a key role in cancer and the neutrophil-to-lymphocyte ratio (NLR) in blood has been suggested as a prognostic factor for OPSCC. This study aimed to investigate the prognostic impact of NLR on overall survival (OS) and recurrence-free survival (RFS) in a retrospective cohort of 1370 patients. Included patients had pretreatment neutrophil and lymphocyte counts available, as well as a known HPV status. Patients were treated with curative intent according to Danish national guidelines. We stratified patients in groups by NLR < 2, NLR 2–4, or NLR > 4 and analyzed the influence of the NLR tertile on OS and RFS. Kaplan–Meier curves illustrated survival probability in OS and RFS in the general cohort and were stratified by HPV status. We found that an increasing NLR was associated with inferior OS (HR = 1.5 for NLR > 4) and RFS (HR = 1.6 for NLR 2–4; HR = 1.8 for NLR > 4) in multivariable analysis. The Kaplan–Meier curves displayed inferior OS and RFS with an increasing NLR for both HPV+ and HPV− patients. In conclusion, we showed that an increasing NLR is prognostic for a worse outcome of OPSCC independently of HPV status. There are possible uses of NLR in prognostication and treatment de-escalation although further studies are warranted to determine the clinical utility. [ABSTRACT FROM AUTHOR]

Second primary cancer (SPC) is the second most common cause of death among patients diagnosed with head and neck cancer. This study examined the risk of SPC following oropharyngeal squamous cell carcinoma (OPSCC) and the impact of human papillomavirus (HPV) on survival following SPC. The study was a population-based, retrospective study including all patients diagnosed with OPSCC in eastern Denmark from 2000–2020 who received curative intended treatment. The incidence rate ratio (IRR), age-adjusted incidence rates (AAIR), and hazard ratios (HR) were calculated. A total of 2584 patients with primary OPSCC were included (median follow-up time: 3.1 years), with 317 patients (12.3%) diagnosed with SPC. The risk of SPC was approximately five times the occurrence of cancer in the general population (IRR: 4.96). The median time to SPC after a primary OPSCC was 2.0 years (interquartile range (IQR) = 0.6–4.2 years). HPV-positive (HPV+) patients had a significantly longer median time to SPC, and a significant better survival compared to HPV-negative (HPV-) patients. SPC was most frequently found in lungs, head, and neck (LHN) for HPV- OPSCC patients and lungs followed by gender-specific (prostate, ovaries, or endometrium) for HPV+ OPSCC. There was a significant difference between the two groups when distributed between "within" or "outside" LHN. Patients with SPC outside LHN had a significant better overall survival. This knowledge should be considered during post-treatment surveillance and might guide targeted imaging. [ABSTRACT FROM AUTHOR]

Days Alive and Out of Hospital (DAOH) is a recently introduced, readily obtainable postoperative outcome measure method that expresses procedure and disease-associated morbidity and mortality. In this study, we evaluated DAOH with 30- and 365-days follow-up periods after primary surgery (DAOH30 and DAOH365, respectively) for patients with oral cavity squamous cell carcinoma (OSCC). The aim of this study is to identify patient-, procedure- and disease-associated risk factors for patients treated with primary surgery for primary OSCC. This retrospective cohort study from a prospective collected database represents patients from Eastern Denmark surgically treated for primary OSCC in the period 2000–2014. DAOH30 and DAOH365 were calculated and associations with patient characteristics including comorbidity, tumor characteristics, clinical outcomes such as length of stay, readmission, and mortality were evaluated. Tests for difference and significance between groups were assessed with Mann–Whitney U test and quantile linear regression. We included 867 patients (63% males, median age: 63 years (IQR 56–70 years)). Median DAOH30 and DAOH365 after OSCC surgery were 25 days (IQR 21–27 days) and 356 days (IQR 336–360 days), respectively. Alcohol consumption had a significant association with a lower DAOH365, p < 0.01, but not with DAOH30. Advanced T-stage, adjuvant radiotherapy (RT) and increased Charlson Comorbidity Index (CCI) score was significantly associated with a lower DAOH30 and DAOH365. In this population-based study in OSCC patients treated with primary surgery, we found that DAOH after 30 days was 25 days (83%), while DAOH after 365 days was 356 days (98%). Advanced T-stage acts as a predictor for significant DAOH30 and DAOH365 reduction while excessive alcohol consumption predicts a significant DAOH365 reduction. Readmission within 30 days following surgery was associated with further readmission within one year. [ABSTRACT FROM AUTHOR]

Second primary cancer (SPC), defined as a metachronous solid cancer resulting from neither a recurrence of the primary cancer nor a metastasis, is a leading long-term cause of death for survivors of primary oral squamous cell carcinoma (OSCC). This study examined the risk of SPC following treatment of primary OSCC. This semi-national, population-based, retrospective study included all patients with primary OSCC treated with curative intent in Eastern Denmark in 2000–2014. The presence of SPC was confirmed from medical records and the Danish Pathology Data Bank. The rate of SPC was compared to the occurrence of any cancer in the Eastern Danish population using data from the Danish Cancer Registry. A total of 936 patients with primary OSSC were enrolled. Of these, 219 patients (23%) were diagnosed with SPC during the follow-up (median 8.9 years, IQR: 5.4–12.6 years). The rate of SPC was four times higher than the occurrence of any cancer among the Eastern Danish population i.e., with a standardized incidence ratio (SIR) of 4.13 (95%CI: 3.55–4.80). SPCs were most frequently found in head and neck region (n = 97, SIR = 43.6), lower respiratory organs (n = 38, SIR = 5.6) and gastrointestinal organs (n = 33, SIR = 3.2) with increased SPC rates in all locations. Among patients who developed SPC within the study period the median time from OSCC to the first SPC was 4.4 years (IQR: 2.5–6.2). Significant associations were found between both smoking and excessive alcohol consumption after treatment of OSCC and the risk of SPC. A noteworthy increased rate of SPC following treatment of primary OSCC was found, especially in the head and neck region and in the lungs. Healthcare professionals should be aware of this increased risk. [ABSTRACT FROM AUTHOR]

The article responds to comments on a study about oropharyngeal cancer in a high HPV-prevalent area in Denmark from 2000 to 2020. The authors acknowledge the potential impact of HPV vaccination on changing epidemiological trends and emphasize the importance of further research on its long-term effects. They also highlight the significance of continuous education and communication to raise awareness about HPV-driven oropharyngeal cancer and the benefits of vaccination. Additionally, the authors discuss the potential of a minimally invasive liquid biopsy method for the follow-up of patients with HPV-positive oropharyngeal cancer, aiming to improve survival outcomes and enhance future diagnostic testing. [Extracted from the article]

This article aims to evaluate the impact of smoking status, accumulated tobacco exposure (ATE), and smoking cessation on overall- and disease-free survival (OS and DFS) of patients with oral squamous cell carcinoma (OSCC). Patients with primary OSCC treated with curative intent between 2000 and 2019 in Copenhagen were included (n = 1808). Kaplan–Meier curves and multivariable Cox regression analyses were performed to compare the survival of patients with different smoking history. Interactions between ATE and (A) tumor subsite and (B) excessive alcohol consumption (EAC) on the survival were evaluated using multivariable Cox regression analyses with interaction terms. We included 1717 patients with known smoking status (62.8% males, median age: 64 years (IQR: 57–71 years)), who had a 5-year OS of 53.7% (95%CI: 49.8%–57.9%). Based on fully adjusted multivariable Cox regression analyses, significantly elevated hazard ratios (HRs) for OS and DFS were identified for current, but not former smokers, compared to never-smokers. An approximately linear relationship between continuous ATE and survival estimates was identified. ATE analyzed as a categorical variable showed significantly elevated HRs for OS of patients with all categories (0 < x ≤ 30, 30 < x ≤ 60, and > 60 PYs), however only for DFS of patients with >60 PYs, compared to 0 PYs. Furthermore, an unfavorable long-term prognosis was evident after >3.5 (OS) and >2.5 (DFS) years from diagnosis for patients who continued smoking compared to patients with smoking cessation at diagnosis. The survival estimates of patients with different tumor subsite and alcohol consumption differed with increasing ATE. Tobacco smoking (assessed as smoking status and ATE) was associated with inferior survival (OS and DFS) among patients with OSCC. Unfavorable long-term prognosis was significant for patients who continued smoking compared to patients with smoking cessation at diagnosis. The impact of ATE on survival of patients with OSCC may depend on the tumor subsite and/or alcohol consumption. [ABSTRACT FROM AUTHOR]

The increases observed in incidence and survival of oropharyngeal squamous cell carcinoma (OPSCC) have been attributed to human papillomavirus (HPV) infection, but the survival‐impact of specific genotypes is poorly understood. We investigated the potential influence of HPV genotypes on survival in HPV‐positive (HPV+) OPSCC. All patients with HPV+/p16+ OPSCC and available genotype data within the period 2011 to 2017 in Eastern Denmark were included. Descriptive statistics on clinical and tumor data, as well as overall survival (OS) and recurrence‐free survival (RFS) with Cox hazard models and Kaplan‐Meier plots were performed. Overall, 769 HPV+/p16+ OPSCC patients were included of which genotype HPV16 accounted for 86% (n = 662). Compared to high‐risk non‐HPV16 genotypes (HR non‐HPV16), HPV16 patients were younger at diagnosis (median years, 60 vs 64), had a higher male to female ratio (3.7:1 vs 2.1:1), and lower performance scores of ≤1 (90%, n = 559, vs 81%, n = 74). Regarding 5‐year OS and RFS, no difference was observed between HPV16 and HR non‐HPV16 patients. Subgrouping the HR non‐HPV16 group into HPV33 (n = 57), HPV35 (n = 26) and "other genotypes" (n = 24) a significantly worse OS in the "other genotypes" group (hazard rate: 2.33, P =.027) was shown. With similar survival results between HPV16 and non‐HPV16 genotypes, genotyping in OPSCC is interesting from an epidemiological point of view as well as in vaccination programs, but not a necessary addition in prognostication of HPV+/p16+ OPSCC. [ABSTRACT FROM AUTHOR]

Several recent observational studies have linked low‐dose aspirin use to improved survival in patients with head and neck cancer. However, studies of patterns of aspirin use and risk of cancer‐specific mortality are lacking. This nationwide cohort study included all patients in the Danish Cancer Registry with a primary diagnosis of head and neck squamous cell cancer (HNSCC) during 2000 to 2016, aged 30 to 84 years, without prior cancer (except nonmelanoma skin cancer) and alive 1 year after diagnosis. Nationwide registries provided information on filled prescriptions, mortality and potential confounding factors. For a subpopulation, a clinical database provided additional information, including human papillomavirus (HPV) tumor status. We used Cox proportional hazards regression models to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between postdiagnostic low‐dose aspirin use (≥1 prescription within first year after diagnosis) and risk of cancer‐specific mortality. We identified 10 770 patients with HNSCC during a median follow‐up of 3.9 years. Of these, 1799 (16.7%) were low‐dose aspirin users. Postdiagnostic use of low‐dose aspirin was associated with a HR of 0.97 (95% CI 0.82‐1.15) for cancer‐specific mortality. Similar neutral associations were found according to patterns of aspirin use. No apparent trends emerged according to age, sex, topography or stage. A tendency towards a decreased cancer‐specific mortality risk with low‐dose aspirin use was observed among HPV‐positive patients; however, the statistical precision was low. In conclusion, we did not observe an association between postdiagnostic low‐dose aspirin use and cancer‐specific mortality in a nationwide cohort of patients with HNSCC. What's new? Long‐term use of low‐dose aspirin is associated with improved all‐cause survival in patients with head and neck squamous cell carcinoma (HNSCC). The relationship between low‐dose aspirin and cancer‐specific mortality, however, remains unclear. In this nationwide cohort study, associations between low‐dose aspirin use and cancer‐specific mortality were evaluated in patients with HNSCC. No associations were observed between post‐diagnostic low‐dose aspirin use and cancer‐specific mortality. Nor were modifying effects observed for patient age and sex, tumor topography and stage, or patterns of aspirin use. Additional studies are needed to elucidate possible associations with HPV‐positive OPSCC. [ABSTRACT FROM AUTHOR]

Single‐cell RNA sequencing (scRNA‐seq) is a novel method enabling genetic characterization of tumor tissue at a single‐cell level. This study systematically reviewed the literature on studies using scRNA‐seq to characterize head and neck squamous cell carcinomas (HNSCCs). Seven studies were included, of which two studies performed scRNA‐seq on 20 patients in total, and five studies used scRNA‐seq data in a subsequent clinical study. The former mentioned two studies found intra‐tumoral genetic heterogeneity among malignant cells but genetic uniformity among non‐malignant cells. The five latter studies used scRNA‐seq data in various ways. Three studies identified biomarkers related to predicting whether a patient would benefit from immunotherapeutic treatment. One study characterized genes related to the perineural invasion. One study identified genes to be used in diagnostics. Further studies performing scRNA‐seq on HNSCC are required to continue the ongoing development and use of scRNA‐seq. [ABSTRACT FROM AUTHOR]

Background: In risk assessment of recurrence, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are often grouped together as differentiated thyroid cancer (DTC). However, while risk factors affecting recurrence of PTC are well established, risk factors for recurrence of FTC are not. This systematic review examines risk factors for recurrence of FTC and evaluates their significance. Methods: A systematic search on PubMed and Embase was performed in September 2020, including studies evaluating risk factors for recurrence of FTC. A quality assessment of the enrolled studies was performed. Results: Nine studies (n = 1544 patients) from eight countries were included. The average recurrence rate was 13.6%, and distant metastasis (DM) constituted 64.8% of the recurrent cases. The risk factors examined were sex, age at diagnosis, primary tumor size, degree of invasiveness, focality, positive resection margin, lymph node (LN) metastasis, and DM at diagnosis. Risk factors correlated with recurrence of FTC were age older than 45 years, primary tumor size above 40 mm, widespread invasion, multifocality, positive resection margin, LN metastasis, and DM at diagnosis. Sex was not a statistically significant risk factor. Conclusions: We identified seven risk factors associated with recurrence of FTC. Age and multifocality were found to be of greater impact regarding recurrence risk of FTC compared with PTC. Future research needs to address the impact of different risk factors for recurrence of FTC particularly including age, primary tumor size, angioinvasion, and mutational status. [ABSTRACT FROM AUTHOR]

This study aimed to systematically review the literature on the impact of delay in diagnosis and treatment of oral cavity cancer. PubMed and Embase were systematically searched for articles reporting impact of delay in diagnosis and treatment on cancer-stage and survival of oral cavity cancer. Studies comprising at least ten patients, and published since the year 2000, were included. Sixteen studies (n = 45,001, range: 62–18,677 per study, 83% men), from Australia, Asia, Europe, North America and South America, met the inclusion criteria. Eleven studies (n = 1,460) examined delay in diagnosis, while five studies (n = 43,541) reported delay in treatment. Eight of the eleven studies, examining delay in diagnosis (n = 1,220), analyzed the correlation between delay in diagnosis and tumor stage at diagnosis. Three studies found a significant correlation between patient delay and advanced stage at diagnosis (p < 0.05), whereas three other studies did not. The studies reporting a significant correlation were from Asian countries, whereas the three studies that did not find a correlation were from other continents. Studies reporting on professional delay and total diagnostic delay, generally, did not find a significant correlation with advanced cancer at diagnosis. Time to treatment (TTI), defined as time from diagnosis to treatment, was found significantly correlated with survival in three studies (p < 0.01, p < 0.001, p < 0.05), and nonsignificant in two studies. A significant correlation between patient delay and advanced stage cancer was reported in Asian studies only, while professional delay and total diagnostic delay were generally found to be non-correlated with advanced stage cancer at diagnosis. TTI was in some studies reported to be correlated with poorer outcome, while other studies did not report a correlation. One study presented that there was no clear advantage in overall survival (OS) for patients treated within 30 days, compared to patients treated between 30 and 44 days. [ABSTRACT FROM AUTHOR]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)