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Anne Gedebjerg,1 Karina Frahm Kirk,2 Pernille Overgaard Lassen,3 Dóra K Farkas,4 Kirstine K Søgaard1,4,5 1Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 3Department of Clinical Medicine, North Denmark Regional Hospital, Hjørring, Denmark; 4Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Kirstine K Søgaard, Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark, Email kirstine.soegaard@rn.dkBackground: Real-world data in form of routinely collected clinical data are a valuable resource for epidemiological research in infectious disease. We examined the validity of a discharge diagnosis of fever of unknown origin from hospital discharge registries.Methods: We identified patients with a first in- or outpatient diagnosis (primary or secondary) of fever of unknown origin (ICD-10 code R50.0; R50.8, R50.9) recorded in the Danish National Patient Registry (DNPR) between 2010 and 2017 in the North Denmark Region. We based the validation cohort on a mix of patients diagnosed at a highly specialized university department of infectious diseases (n=100), other internal medicine departments (n=50), and patients diagnosed at a regional non-university hospital (n=50). We estimate positive predictive value (PPV) of diagnosis for fever of unknown origin using medical records as reference.Results: The PPV of a diagnosis of fever of unknown origin for patients diagnosed at the infectious disease department was 61% (95% CI: 51– 71%). For other internal medicine departments, it was 14% (95% CI: 6– 27%), and for the non-university hospital it was 16% (95% CI: 7– 29%). To achieve higher PPVs, we excluded immunocompromised patients, patients who were diagnosed with infection, cancer or rheumatic disease within 7 days after admission, and/or patients with a short hospital stay (maximum 3 days) and no subsequent hospital contact within 1 month. The PPV for diagnoses from the Department of Infectious Diseases improved to 82% (95% CI: 68– 91%) for other internal medicine departments it improved to 31% (95% CI: 11– 59%), and for the non-university hospital it improved to 36% (95% CI: 13– 65%).Conclusion: We found that only diagnoses made in the Department of Infectious Diseases accurately identified fever of unknown origin, whereas diagnoses made in other units mainly covered infection-related fever, cancer-related fever, or short unspecific fever without further diagnostic work-up.Keywords: fever of unknown origin, positive predictive value, validation studies

ImportanceThe socioeconomic gap in survival after cancer is pronounced among patients with head and neck cancer. Understanding the mechanisms of this gap is crucial to target intervention strategies.ObjectiveTo investigate socioeconomic differences in survival after oropharyngeal squamous cell carcinoma (OPSCC) according to human papillomavirus (HPV) status and the extent to which smoking, comorbidity, clinical stage, and treatment intent explain the survival gap.Design, Setting, and ParticipantsThis nationwide, population-based cohort study was based on prospectively collected information on all patients with a diagnosis of OPSCC from the Danish Head and Neck Cancer Group database and administrative registries. The study included 4600 patients born in 1921 or later, aged 30 years or older, and residing in Denmark 1 year prior to OPSCC diagnosis. Patients with missing information (547 [12%]) were excluded. Patients were diagnosed between January 1, 2008, and December 31, 2019, and followed up until December 31, 2021. Data were analyzed from June 6 to October 4, 2022.ExposureSocioeconomic position (educational level, disposable income, or cohabiting status).Main Outcomes and MeasuresSocioeconomic differences in 5-year overall survival were estimated in Cox proportional hazards regression models by HPV status. The indirect effect and proportion mediated by smoking, comorbidity, clinical stage, and treatment intent were estimated based on a counterfactual approach.ResultsThe analyzed cohort comprised 4053 patients (1045 women [26%] and 3008 men [74%]). The median age was 61 years (IQR, 55-68 years), and 2563 patients (63%) had HPV-positive OPSCC while 1490 patients (37%) had HPV-negative OPSCC. The 5-year standardized overall survival was 10% to 15% lower among patients with a lower educational level, with low disposable income, or who were living alone (patients with HPV-positive OPSCC, 68%-71%; patients with HPV-negative OPSCC, 31%-34%) than patients with a higher educational level, high disposable income, or a cohabiting partner (patients with HPV-positive OPSCC, 81%-86%; patients with HPV-negative OPSCC, 43%-46%). Among patients with HPV-positive OPSCC, a considerable part of this survival gap was estimated to be associated with differences in smoking (27%-48%), comorbidity (10%-19%), clinical stage (8%-19%), and treatment intent (16%-28%). Among those with HPV-negative OPSCC, comorbidity (12%-22%) and treatment intent (16%-42%) were the primary potential mediators.Conclusions and RelevanceThis cohort study suggests that, regardless of HPV status, patients with low socioeconomic position had 10% to 15% lower 5-year overall survival than patients with high socioeconomic position. A substantial part of this survival gap was associated with differences in smoking, comorbidity, clinical stage, or treatment intent at diagnosis.

Additional file 1: Table S1. Medications used at the time of admission

Background: Expression of p16 is highly correlated to infection with Human Papillomavirus in squamous cell carcinoma of the head and neck (HNSCC). Previous reports have demonstrated an inverse correlation between expression of epidermal growth factor receptor (EGFR) and p16 in HNSCC. The aim of this study was to examine the correlation between EGFR and p16 and to asses their influence on response to radiotherapy (RT) and survival in a large cohort of HNSCC patients treated with RT alone in the randomised DAHANCA 5, 6& 7 trials.Material and Methods: Between January 1986 and December 1999 The Danish Head and Neck Cancer group (DAHANCA) conducted the nationwide DAHANCA 5, 6& 7 randomised trials, focusing on overcoming the disadvantages of tumour cell hypoxia and accelerated tumour cell proliferation in relation to RT. In the present study 1088 pre-treatment tumour tissues from patients in these trials were examined by immunohistochemistry for EGFR-expression (high/low) and p16 status (pos/neg).Results: In total 258 of 1088 (24%) tumours were p16pos and 885 (81%) had high EGFR-expression. The correlation between EGFR and p16 was found to be inverse with p16pos tumours tending to have lower EGFR-expression (27%) compared to p16neg tumours (16%, pppp