Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer

AbstractBackground and purposeHPV is found in head and neck cancer from all sites with a higher prevalence in oropharynx cancer (OPC) compared to non-OPC. HPV/p16-status has a significant impact on radiotherapy (RT) outcome in advanced OPC, but less is known about the influence in non-OPC. We analyzed HPV-associated p16-expression in a cohort of patients with stage III–IV pharynx and larynx cancer treated with primary, curatively intended (chemo-)RT, aiming to test the hypothesis that the impact of HPV/p16 also extends to tumors of non-oropharyngeal origin.Material and methods1294 patients enrolled in previously conducted DAHANCA-trials between 1992 and 2012 were identified. Tumors were evaluated by p16-immunohistochemistry and classified as positive in case of staining in >70% of tumors cells.ResultsThirty-eight percent (490/1294) of the tumors were p16-positive with a significantly higher frequency in OPC (425/815) than in non-OPC (65/479), p<.0001. In OPC p16-positivity significantly improved loco-regional control (LRC) (adjusted HR [95% CI]: 0.43 [0.32–0.57]), event-free survival (EFS) (HR 0.44 [0.35–0.56]), and overall survival (OS) (HR: 0.38 [0.29–0.49]), respectively, compared with p16-negativity. In non-OPC no prognostic impact of p16-status was found for either endpoint: LRC (HR: 1.13 [0.75–1.70]), EFS (HR: 1.06 [0.76–1.47]), and OS (HR: 0.82 [0.59–1.16]).ConclusionsThe independent influence of HPV-associated p16-expression in advanced OPC treated with primary RT was confirmed. However, RT-outcome in the group of non-OPC did not differ by tumor p16-status, indicating that the prognostic impact may be restricted to OPC only

Fever of Unknown Origin:A Validation Study of Danish ICD-10 Diagnosis Codes

BACKGROUND: 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.</p