Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma.

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration. Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed. Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006). Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.

Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. METHODS: This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. RESULTS: With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) - vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). CONCLUSION: Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies.

[Otolaryngology-knowledge among ORL-physicians: An analysis of the quiz questions in the ORL-App]. / HNO-Wissen bei HNO-Ärzten: Eine Analyse der Quizfragen in der HNO-App.

BACKGROUND: The ORL-App, a smartphone app for further education and training for ORL doctors and those interested in ORL, complements existing offers in medical education and training. The principle of game-based e-learning can open up new perspectives in times of digitalisation and pandemic. The heart of the app is a large ORL quiz, in which app users compete against each other. This paper analyses the performance of app users in the quiz module, taking into account the questions' categories and the users' level of education. MATERIAL AND METHODS: Retrospectively, an evaluation of the quiz questions was carried out for the first 24 months after the introduction of the app. There were 3593 different questions to choose from in 16 different categories. Based on the level of training, a distinction was made between doctors in further training, specialists, senior physicians, chief physicians and professors in the field of ORL. In addition, data on students and non-medical staff were available. RESULTS: There was a significant difference in the level of knowledge of the users considering the level of training. The group of doctors in further training (n = 1013) represented the largest group, with an average of 244 questions per user and 65.1% of the questions answered correctly. They thus achieved a significantly better answer rate than the group of specialists (n = 566), who were able to answer 61.0 % of the questions correctly. CONCLUSION: The game-based form of training through the quiz-part of the ORL-App seems to be particularly attractive for doctors in further training. In addition, this user group achieved better answer rates than the specialists.