Claus Andrup Kristensen

Background and purpose: This study investigated prognostic biomarkers in oropharyngeal squamous cell carcinoma (OPSCC), with a focus on tumors related to human papillomavirus (HPV) infection and potential molecular effects of tobacco smoking, as smokers with HPV+ OPSCC often have poorer outcomes. Patients/material and methods: We first analyzed 56 previously untreated OPSCC patients (exploration cohort), assessing HPV status, gene expression related to hypoxia, tumor subtype, and radiosensitivity, together with next-generation sequencing (NGS) of cancer-related genes. A custom NGS panel was subsequently designed and validated in 162 patients from the DAHANCA 19 randomized controlled trial (RCT), all treated with curative (chemo-)radiotherapy. Results:In the exploration cohort (40 HPV+, 79%), the most common molecular events in HPV+ tumors were PIK3CA and ATR mutations and chromosome 3q amplification. ATR and CREBBP mutations occurred more often in heavy smokers (>10 pack-years), but these associations were not confirmed in the DAHANCA 19 cohort. No specific smoking-related mutational signature or link to TP53 mutations was observed. In the DAHANCA 19 cohort, 17 locoregional failures (LRF) occurred among 128 HPV+ patients. No unifying molecular features were identified. However, mutations in NFE2L2 and CASP8, as well as amplifications of 3q genes (BCL6, SOX2), were associated with LRF. Interpretation: In HPV+ OPSCC, only few molecular alterations appear to act as drivers or prognostic biomarkers. Importantly, no molecular features of tobacco smoking exposure were identified, and the mechanism behind the worse prognosis in smokers remains unclear.

Background and purpose: The randomised clinical trial KEYNOTE-048 has demonstrated a significant increase in survival for patients with head and neck cancer treated with pembrolizumab with or without chemotherapy. The purpose of the present retrospective study was to investigate whether survival in a group of consecutive patients treated at our department was comparable to the results from KEYNOTE-048. Patients/material and methods: Seventy-six patients initiated treatment with pembrolizumab ± platinum/5-FU between July 2020 and May 2022. Baseline characteristics were collected, response rates and survival times were calculated and compared to those published from KEYNOTE-048. Results and Interpretation: Fifty-one percent of patients had locoregional recurrence and 47% had distant metastases. Median progression-free survival was 5.5 months, and median overall survival (OS) was 12.3 months in the total cohort. OS was significantly higher for patients with combined positive score (CPS) ≥20 (14.6 months) than for patients with CPS 1–19 (7.3 months) (p = 0.04). There was no significant difference in survival times between patients ± 65 years of age or between patients with locoregional disease versus distant metastases. In conclusion, the results from KEYNOTE-048 were corroborated in a consecutive cohort of patients treated at Rigshospitalet, Copenhagen, Denmark.

The prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19. We included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel. HPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected.Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status (p < 0.0001 for all) and did not depend on HPV genotype (p = 0.9 and p = 0.7). In the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator.

The socioeconomic differences in survival are pronounced for patients diagnosed with head and neck cancer; disease stage at diagnosis is suggested to be a main driver of this association. This nationwide, population-based study investigates socioeconomic differences in the pre-diagnostic interval and disease stage at diagnosis. Information on patient-reported symptoms, symptom onset and disease-specific factors was obtained from the nationwide population-based Danish Head and Neck Cancer Group (DAHANCA) database for patients diagnosed with head and neck squamous cell carcinoma between 2008 and 2019 in Denmark. Socioeconomic position (SEP) was measured by individual-level education, income and cohabitation status obtained from administrative registers. Socioeconomic differences in the interval from symptom onset to diagnosis were investigated in general linear models with 95% confidence intervals (CIs); overall and by subsite, symptom and comorbidity score. Consultation patterns prior to diagnosis were examined using methods for change-point detection. Associations with advanced-stage disease were estimated in logistic regression models. Patients with low, medium and high SEP had a similar interval from patient-reported symptom onset to diagnosis of 10 weeks. Although this interval varied according to primary symptom and anatomical subsite, no apparent socioeconomic differences were observed within these subgroups. Aligned with the patient-reported symptom onset, a distinct increase in consultation rates was observed at 9 weeks (95% CI [7.3; 10.7]) for patients with low SEP and 7 weeks (95% CI [4.8; 9.2]) for patients with high SEP, with overlapping CIs. Patients with low compared to high SEP had increased odds for advanced-stage glottic and oral cavity squamous cell carcinoma. For the remaining subsites the association varied according to SEP-indicator and TNM-edition. The interval from symptom onset to diagnosis and consultation patterns were similar across SEP groups. Still, socioeconomic differences in stage at diagnosis were observed for some - but not all - subsites.

"Introducing canine lifestyle medicine and access to care in context of an interprofessional framework" published on 14 May 2023 by American Veterinary Medical Association.