Detection of antibody subclasses IgA, IgM and IgG against HPV L1 in HPV-positive oropharyngeal squamous cell carcinoma patients: a pilot study.

PURPOSE: Despite prognostic superiority of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), up to 25% of patients will suffer from recurrence within the first 5 years. Therefore, it is of great scientific interest to find relevant biomarkers to identify patients at risk. In this prospective observational study, we aimed to investigate the dynamics of HPV-L1 capsid protein specific antibody (AB) subclasses IgA, IgM, and IgG in HPV-positive OPSCC patients under therapy. METHODS: Serum samples from HPV-positive OPSCC patients, identified by positive p16-immunohistochemistry, were collected before and during tumor-specific therapy and 3-6 months during follow-up. They were analyzed for the presence of HPV-L1 AB subclasses IgA, IgM, and IgG using an HPV-L1-specific immuno-assay. Additionally, a PCR-based HPV-DNA detection from the tumor tissue was performed. RESULTS: Altogether, 33 patients with a mean follow-up of 55 months were included. Analysis of a total of 226 serum samples revealed that the most common L1-AB-subclass pattern was characterized by IgG > > IgA > IgM without significant fluctuation during the course of disease. Patients with excessive IgG levels tended to higher tumor stages and three out of three patients with disease recurrence showed increasing IgG AB titers beforehand. Seven patients showed an IgA dominance at diagnosis, which was associated with a better disease-free survival. CONCLUSION: Despite limited cases, our prospective pilot study revealed promising trends in HPV L1 AB subclasses and may contribute useful information for future risk stratification and post-treatment monitoring in HPV-positive OPSCC patients.

Endoscopic trans-sphenoidal pituitary surgery does not impact postoperative nasal quality of life.

PURPOSE: The aim of this prospective longitudinal study was to assess both subjective quality of life using questionnaires and objective examination of nasal function with regard to olfaction, nasal air flow and mucociliary clearance in patients after minimally invasive, turbinate-preserving endoscopic transnasal trans-sphenoidal pituitary surgery. METHODS: Patients undergoing endoscopic transnasal pituitary surgery were recruited prospectively and examined during three study visits, preoperatively and 3 and 6 months postoperatively. We examined nasal function using sniffin' sticks test, rhinomanometry, saccharin transit time test, and endoscopic and radiological scores. In addition, the influence on subjective quality of life and mental health was recorded using the Sinonasal-Outcome-Test-20 (SNOT-20) and the Hospital-Anxiety-and-Depression-Scale (HADS). RESULTS: 20 patients undergoing endoscopic pituitary tumor resections were included. No significant changes in olfaction or mucociliary clearance were noted. Nasal air flow showed a tendency to increase in the postoperative course lacking significance. Both the endoscopy and the radiological scores showed a significant deterioration, especially after 3 months, with a trend towards improvement over time. However, neither the SNOT-20 nor the HADS showed significant changes compared to baseline. CONCLUSIONS: Our concept of minimally invasive endoscopic tumor resections on the pituitary gland with preservation of nasal turbinates shows low morbidity for the patient. Despite objectifiable surgery-associated changes in the nose, nasal physiology in terms of smell, airflow and mucociliary clearance can be preserved and the subjective quality of life of our patients remains stable.

Preservation of nasal turbinates in endoscopic, anterior skull base surgery-yes, we can!

OBJECTIVE: To evaluate the frequency, type and indications of nasal turbinate (NT) resection during endoscopic, anterior skull base surgery and to analyze factors that may have an impact on the need of NT removal. METHODS: In this retrospective cohort study, 306 subjects (150 males and 156 females, mean age 55.4 ± 15.3 years) who underwent multidisciplinary, transnasal, endoscopic tumor surgery of the anterior skull base using 4-handed techniques between 2011 and 2019 at the Department of Otorhinolaryngology, Medical University of Graz, were included. RESULTS: In the majority of interventions (n = 281/306; 91.8%), all NT were preserved. Significant factors influencing the need of NT resections turned out to be type of endoscopic approach (p < 0.001; V = 0.304), sagittal (p = 0.003; d = 0.481) and transversal (p = 0.017; d = 0.533) tumor diameter, tumor type (p < 0.001; V = 0.355) and tumor location (p < 0.001; V = 0.324). CONCLUSIONS: NT can be preserved in the majority of patients undergoing tumor resection in anterior, transnasal, skullbase surgery and routine resection of NT should be avoided. Variables that have an impact on the need of NT resections are types of endoscopic approaches, sagittal and transversal tumor extension and tumor type. These factors should be considered in planning of surgery and preoperative information of patients.

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma.

AIMS: Because the hedgehog signalling pathway plays a major role in many types of cancer and can nowadays be targeted by specific compounds, we aimed to investigate the role of this pathway in squamous cell carcinoma of the head and neck. METHODS AND RESULTS: Ninety-eight treatment-naive head and neck cancer specimens were immunohistologically stained for SMO, GLI-1, p53 and p16 expression and correlated with clinicopathological factors. Immunoreactivity for SMO and GLI-1 was found in 20 (20.4%) and 52 (53.1%) cases of tumours, respectively. SMO expression correlated with GLI-1 expression (ρ = 0.258, P = 0.010) in univariate and multivariate analysis (P = 0.007, t = 2.81). In univariate analysis, high SMO expression was associated with shorter overall survival (HR = 0.56; 95% CI = 0.32-0.98; P = 0.044) and disease-free survival (HR = 0.53; 95% CI = 0.30-0.95; P = 0.034). In multivariate cox regression analysis SMO expression showed a trend towards an independent predictor for shorter overall survival (HR = 0.57; 95% CI = 0.30-1.05; P = 0.072) and disease-free survival (HR = 0.53; 95% CI = 0.28-1.02; P = 0.056). In head and neck cancer patients with low tumour p16 expression, SMO expression was an independent factor for overall survival (HR = 0.49; 95% CI = 0.24-0.98; P = 0.043) and disease-free survival (HR = 0.45; 95% CI = 0.22-0.96; P = 0.037). CONCLUSION: Although it needs to be confirmed in larger cohorts, our results suggest that targeting SMO might be a potentially therapeutic option in patients with head and neck cancer. In line, molecular pathological analyses including mutation analysis in the hedgehog pathway might point to additional therapeutic leads.

Earlobe Correction of the Pierced Ear: A Systematic Review of the Literature and Principles for Surgical Reconstruction.

Background: Surgical reconstruction of the earlobe after gauge ear piercing can be challenging especially in cases of large defects. Objective: By performing a systematic review of the current literature, we aimed to identify available surgical approaches for earlobe reconstruction after gauge piercing and provide a surgical classification system with regard to defect size. Methods: A literature review was performed including MEDLINE and PubMed databases to identify articles describing reconstruction after stretched earlobe piercing. Articles referring to traumatic, congenital, and acquired cleft deformities were excluded. Surgical techniques were summarized and categorized with regard to different defect sizes. Drawings of each method were performed. Results: A total of 17 different surgical approaches were found and described. Based on the authors' descriptions of each technique, a classification system for small to medium, large, and extralarge defects was established and special benefits of each method were highlighted. Conclusion: A simple classification of available techniques for stretched earlobe reconstruction with regard to defect size might help physicians to choose the appropriate surgical management especially in cases of large defects.

Trichoblastic carcinosarcoma of the neck: Case report and molecular analysis of a seldom, relapsing entity and a review of the literature.

Trichoblastic carcinosarcoma is a seldom biphasic adnexal tumor with malignant epithelial and mesenchymal components. The authors report the first tumor on the neck developed from preexistent trichoblastoma showing aggressive, recurrent behavior. An 82-year-old man presented with a solitary 3-cm exophytic lesion. Histology verified the diagnosis of trichoblastic carcinosarcoma. Four years earlier, a trichoblastic carcinoma arising in a preexisting trichoblastoma was excised at the same location. Despite successful surgical treatments, three local recurrences within 4 years were diagnosed. After the second relapse, the patient agreed on adjuvant radiation. Twelve months later, another relapse was excised in toto. In the last surgical specimen, only the mesenchymal component was found. Copy number variation analysis of the preexisting tumor and two recurrences revealed the same entity and additional chromosomal aberrations in the recurrences. Adnexal carcinosarcomas are seldom, yet presumably underdiagnosed biphasic tumors with aggressive growth potential. They should have adequate preoperative clarification with wide tumor excision, as radiosensitivity seems to be of limited effect.

Combined simulation of a micro permanent magnetic linear contactless displacement sensor.

The permanent magnetic linear contactless displacement (PLCD) sensor is a new type of displacement sensor operating on the magnetic inductive principle. It has many excellent properties and has already been used for many applications. In this article a Micro-PLCD sensor which can be used for microelectromechanical system (MEMS) measurements is designed and simulated with the CST EM STUDIO(®) software, including building a virtual model, magnetostatic calculations, low frequency calculations, steady current calculations and thermal calculations. The influence of some important parameters such as air gap dimension, working frequency, coil current and eddy currents etc. is studied in depth.

Concordance of tumor infiltrating lymphocytes, PD-L1 and p16 expression in small biopsies, resection and lymph node metastases of oropharyngeal squamous cell carcinoma.

OBJECTIVE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC), especially human papillomavirus (HPV)-associated, is increasing worldwide. Immunotherapy become available for patients with carcinomas in the head and neck region, however without ideal biomarker. Markers like PD-L1 vary in the clone of the antibody used, and the method of evaluation. Adequate and reliable immune cells characterization and evaluation is still not found. Furthermore, studies analyzing representativeness of different tissue samples are scarce. We analyzed small biopsy, lymph node (LN) metastasis and resected OPSCC, in regards of tumor infiltrating lymphocyte (TIL) density, PD-L1 and p16 expression. MATERIAL AND METHODS: Patients with OPSCC diagnosed from 2000 to 2016, with small biopsy, resection specimen and LN metastasis samples were selected. We analyzed TILs on hematoxylin-eosin stain, and PD-L1 and p16 expression in tumor cells. Concordance between different tumor locations was evaluated. RESULTS: 93 patients, with 65 small biopsies, 72 resection specimens, and 70 LN metastases were included. TILs, p16 and PD-L1 demonstrated very high concordance. Additionally, PD-L1 expression in the small biopsies was more representative of the PD-L1 expression in the resection specimens, than the LN samples. CONCLUSION: TILs density can be reliably assessed using hematoxylin-eosin stain with high concordance between the small biopsy, resection specimen and LN metastasis. Evaluation of concordance of p16 expression is very high, nevertheless some cases might be misdiagnosed on a small biopsy or lymph node metastasis. Evaluation of PD-L1 expression is very reliable on the biopsy specimen. Different PD-L1 clones and methods of evaluation still remain to be addressed.

Sex-specific differences in patients with nonmelanoma skin cancer of the pinna.

BACKGROUND: Generally, it is known that men are affected more frequently by nonmelanoma skin cancer (NMSC) than women. The aim of our study was to investigate the effect of sex on the characteristics of NMSCs of the pinna at the population that our center serves and to compare it with the international data. METHODS: We analyzed retrospectively the data of 225 patients with NMSC of the pinna. Sex-specific differences were investigated for basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) subgroups. RESULTS: The ratio of BCC to cSCC was determined in male patients at 1:1.3, in contrast in females it was identified at 4:1 (P = .001). CONCLUSION: In our study, a new aspect of the sex-dependent distribution of cSCC and BCC of the pinna was demonstrated. Women are affected four times more frequently by BCC than by cSCC, whereas in men this ratio is approximately equal.

Head and neck cancer in Styria : An epidemiologic and clinical audit.

BACKGROUND: The outcome of patients with cancer of the head and neck is significantly improved by increased interdisciplinary cooperation. The main focus of this study was a comparison of epidemiologic factors (age, sex, origin, staging) of patients with head and neck cancer in Styria, with those for patients throughout Austria. METHODS: A retrospective data analysis of collected archived tumor board protocols of the Comprehensive Cancer Center (CCC) Graz included the patient's age, sex, area of residence, TNM stage, reasons for inoperability, comorbidities and performance status by ECOG (Eastern Cooperative Oncology Group), was performed. This study focuses on 340 patients who presented with a head and neck malignancy for the first time. RESULTS: In the period from January 2014 to December 2015 a total of 252 men (74.1%) and 88 women (25.9%) with malignant head and neck tumors, were presented in the tumor board for the first time. The mean age at diagnosis was 63.4 years. In 45.5% the patients already demonstrated advanced tumor stages (T4 = 27.9%, T3 = 17.6%). Most newly diagnosed neoplasms were cancers of the oropharynx (24.1%), larynx (19.4%) and oral cavity (18.8%) and 36.5% were considered to be inoperable. Curative and palliative treatments were initiated in 83.2% and 16.9%, respectively. CONCLUSION: The region of south Styria showed a higher incidence of T3 and T4 tumors of the oropharynx than the average Austrian population. Measures to increase awareness of this problem should be initiated to support general otorhinolaryngologists and general practitioners in detecting oropharyngeal cancers at an earlier stage.

DRH1 - a novel blood-based HPV tumour marker.

BACKGROUND: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay. METHODS: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO reference-sera for HPV16/18 and 29 pre- and post-immune sera of Gardasil-9-vaccinees. Tumour-tissue was immunochemically stained for HPV-L1-capsidprotein-expression. FINDINGS: The DRH1-competitive-serological-assay showed a sensitivity of 95% (95% CI, 77.2-99.9%) for HPV16-driven HNSCC, and 90% (95% CI, 55.5-99.7%) for HPV16-induced anal cancer in HIV-positives. Overall diagnostic specificity was 99.46% for men and 99.29% for women ≥ 30 years. After vaccination, antibody level increased from average 364 ng/ml to 37,500 ng/ml. During post-therapy-monitoring, HNSCC patients showing an antibody decrease in the range of 30-100% lived disease free over a period of up to 26 months. The increase of antibodies from 2750 to 12,000 ng/ml mirrored recurrent disease. We can also show that the L1-capsidprotein is expressed in HPV16-DNA positive tumour-tissue. INTERPRETATION: HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease. As post-treatment biomarker, the assay allows independent post-therapy monitoring as well as early diagnosis of tumour recurrence. An AUC of 0.96 indicates high sensitivity and specificity for early detection of HPV16-induced disease. FUNDING: The manufacturer provided assays free of charge.