Plasma Cell-Free Human Papillomavirus Oncogene E6 and E7 DNA Predicts Outcome in Oropharyngeal Squamous Cell Carcinoma.

Persistent human papillomavirus (HPV) infection is associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), and increasing incidences of OPSCC are reported. The generally favorable treatment outcome in patients with HPV-driven OPSCC has brought de-escalation of treatment into discussion. Nevertheless, 13% to 25% develop a relapse within two years after current standard treatment. New biomarkers are urgently required to monitor therapy response, tumor burden, and minimal residual disease during follow-up. This observational study examined 50 patients with OPSCC to investigate plasma cell-free (cf) HPV-DNA derived from tumor cells before therapy and during follow-up. Real-time quantitative PCR was applied to quantify the DNA concentration of HPV oncogenes E6 and E7. A total of 85.7% of pretreatment samples from patients with HPV-driven OPSCC (n = 28) were positive for at least one marker, and cfHPV-DNA concentration increased with tumor size. Virtually no signals were detected in HPV-negative OPSCC patients (n = 20; P ≤ 0.001). Patients without clinical evidence of recurrence had significantly reduced cfHPV-DNA concentrations after therapy (P ≤ 0.001). Conversely, cfHPV-DNA levels increased or remained above threshold in five patients who had residual disease or developed recurrence. In conclusion, plasma cfHPV-DNA detection correlates with the clinical course of disease in patients with HPV-driven OPSCC. Consequently, extensive clinical investigation should be considered if cfHPV-DNA is detected during follow-up of patients with HPV-driven OPSCC.

Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation.

BACKGROUND: A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing. METHODS: We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV-DNA, HPV genotypes, p16INK4a expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients' survival in comprehensive uni- and multivariate analyses. RESULTS: Aetiological relevance of HPV (p16INK4a- and high-risk HPV-DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV16 being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16INK4a overexpression but no HPV-DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16INK4a-positive OPSCC lacking HPV-DNA did not resemble HPV16-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16INK4a-overexpressing OPSCC. CONCLUSIONS: p16INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.

[Sialolithiasis: Current Diagnostics and Therapy]. / Sialolithiasis: aktuelle Diagnostik und Therapie.

Sialolithiasis is one of the most common salivary gland diseases. The main symptom is acute swelling of a major salivary gland after food intake, whereby the submandibular gland is significantly more frequently affected compared to the parotid gland. In the course of the disease, recurrent sialadenitis occurs in many cases. In addition to submandibulectomy, there is currently not only the possibility of improved diagnostics but also of gland-preserving therapy, for example by means of miniature endoscopy (sialendoscopy).

[Laryngeal Recurrent Respiratory Papillomatosis: Current Aspects on Diagnosis and Therapy]. / Rezidivierende respiratorische Papillomatose: Aktuelles zu Diagnose und Therapie.

Recurrent Respiratory Papillomatosis (RRP) is a rare infectious disease of the upper aerodigestive tract caused by human papillomavirus (HPV). Virus subtypes 6 and 11 are found in most of the papillomas, type 11 is associated with a severe course. There are a juvenile and an adult form defined by age of initial manifestation. The juvenile form shows a more severe course according to number of surgical interventions and secondary malignancy. A variety of treatment modalities are used to treat RRP. Baseline therapy is a surgical therapy via microlaryngoscopical approach. Extended surgical therapies are not indicated because HPV persists in surrounding tissue of visible lesions. Primary objective is therefore functional preservation of the aerodigestive tract. Adjuvant therapy might be helpful in selected cases, and is actually subject of investigation. HPV vaccination exists and will prospectively change incidence of RRP in the following years.

[Value of sialendoscopy in German ENT-hospitals in 2016]. / Stellenwert der Sialendoskopie an deutschen HNO-Kliniken im Jahr 2016.

OBJECTIVE: In 2009 a nationwide survey revealed that only 24 % of the German ENT-hospitals performed sialendoscopy. In 2016 the survey was repeated to reevaluate the actual ranking of sialendoscopy in Germany. MATERIAL UND METHODS: Again, the same questionnaire as in 2009 was sent to all German ENT-hospitals. It is a self-developed questionnaire including eleven questions. The results from 2009 and the new results from 2016 were matched with each other. RESULTS: The amount of hospitals performing sialendoscopy doubled and the number of interventions tripled. There were various reasons for denying sialendoscopy. Main reason was a lack of patients. No differences were seen in ambulant vs. inpatient interventions and the duration of sialendoscopy. Preoperative ultrasound was performed in all hospitals. CONCLUSIONS: The survey reveals an increasing number of hospitals performing sialendoscopy and an increasing number of sialendoscopies. Simultaneously, some hospitals alleged a lack of patients. These facts could explain a development of specialized centers for obstructive sialadenitis and sialendoscopy. Meanwhile, further salivary gland diseases are treated with sialendoscopy. The preoperative diagnostic of choice is ultrasound. Sialendoscopy seems to be more and more established in German ENT-hospitals.

Dural cell culture. A new approach to study duraplasty.

Fistulas of the cerebrospinal fluid are often repaired by insertion of grafts of various kinds. However, current knowledge of wound healing after graft insertion is limited, and only a few animal studies are available. The objective of this study is to test whether an in vitro model is suited to analyze cellular healing aspects after duraplasty and to assess dura substitutes in such conditions in regard to their surface attractiveness for cellular migration from the dura margins. Harvested dura pieces from minipigs were perforated to mimic central dura lesions, placed on various coated surfaces (collagen, laminin, poly-L-lysine) or grafts, and investigated in a cell culture for cellular closure of the perforation. Cellular migration from the dura into the central perforation was noted on collagen-coated surfaces and when defects were filled with collagen gels, but there was no cell growth on surfaces with poly-L-lysine or laminin coating. Immunocytochemistry identified the migrating cells mainly as fibroblasts with some intermingled epithelial cells. Scanning electron microscopy proved cellular closure of defects after dura placement on allogenic non-crosslinked collagen transplants. Less cellular migration was observed on poly-P-dioxanon sheets, while no cells migrated into the central dura perforation after placement on a cartilage substitute. Cell counting indicated enhanced cellular closure of the dura opening after introduction of insulin or fibroblast growth factor (sign test for both: 0.031). Our study succeeded in establishing a cell culture model for duraplasty and indicated cellular migration from the dura borders at the site of the defect during the wound healing process. The cell culture model presented in this report shows that collagen grafts are best suited for duraplasty. In accordance with the immunocytological finding of fibroblast migration from the dura borders additional application of fibroblast-stimulating growth factors accelerated cellular defect closure.