The 9th edition of the TNM classification represents a refinement of the staging system for oropharyngeal carcinoma. Based on the distinction between HPV-associated and HPV-negative tumors introduced with the TNM-8 classification system, TNM-9 aims to capture the prognostically relevant heterogeneity within the HPV-associated subgroup more precisely. In particular, greater emphasis is placed on nodal disease characteristics, including extranodal extension, to improve prognostic discrimination. This CME article reviews the key factors of the TNM-9 classification for HPV-associated oropharyngeal carcinomas and critically discusses their clinical implication. In addition to formal aspects of staging, diagnostic work-up, the role of imaging, the significance of p16 immunohistochemistry as a surrogate marker, and the impact of smoking and comorbidity are addressed. Cervical carcinoma of unknown primary and nasopharyngeal carcinoma are highlighted as paradigmatic models of biologically integrated staging. The aim of this article is to clarify the prognostic role of TNM-9 while outlining its limitations. Appropriate application requires standardized diagnostic procedures and interdisciplinary interpretation; therapeutic decisions should not be derived from TNM stage alone.

Background The human host factors Secretory leukocyte protease inhibitor (SLPI) and Annexin A2 (AnxA2) influence susceptibility of epithelial cells to human papillomavirus (HPV)-infections. Although nasopharyngeal carcinoma (NPC) is classically associated with Epstein–Barr virus (EBV), increasing evidence indicates that a subset of NPCs from non-endemic regions harbours HPV DNA, suggesting biological overlap with HPV-associated head and neck cancers. Therefore, we studied whether this host-driven mechanism also shapes NPC-biology. Methods Retrospectively 44 histopathological confirmed NPC cases from non-endemic German regions were analysed. Nucleic acids were extracted from FFPE tissue. DNA was used for PCR-based detection of HPV and EBV, RNA was used for RT-PCR detection of HPV transcriptional activity and RT-qPCR for quantification of SLPI- and AnxA2-expression. Associations between viral-status, host factor expression, and clinicopathological parameters were assessed using Fisher’s exact test, Student’s t-test, and one way-ANOVA. Results EBV was detected in 65.9% cases, HPV-DNA in 29.6%, all harboured HPV16-DNA; none expressed HPV16-RNA. EBV-status had no effect on SLPI-expression and was associated with lower AnxA2-levels. HPV-presence was associated with significantly lower SLPI- and higher AnxA2-expression, indicating a permissive epithelial environment for viral entry. Combined-status analyses confirmed that host factor expression paralleled the HPV-DNA- but not EBV-status. Conclusions These findings indicate that in NPC from non-endemic regions, SLPI- and AnxA2-expression defines a host microenvironment permissive for HPV-DNA, whereas EBV-status appears independent of these factors. As no HPV-RNA was detected, these results reflect HPV-presence rather than transcriptionally active infection, suggesting that these host factors may govern viral entry without determining subsequent infection.

Abstract Purpose Sentinel lymph node biopsy (SLNB) is a standard procedure for nodal staging in cutaneous melanoma. However, its diagnostic performance in the head and neck region remains limited due to complex lymphatic drainage patterns. This study aimed to evaluate the long-term diagnostic accuracy of SLNB in head and neck melanoma and to analyze anatomical and clinical factors associated with false-negative results. Methods This retrospective single-center cohort study included patients with cutaneous head and neck melanoma who underwent SLNB between 2002 and 2022. Patients were stratified into two cohorts (2002–2011 and 2012–2022). Detection rates, sensitivity, negative predictive value, and false-negative rates were calculated. Overall survival was analyzed using Kaplan–Meier estimates and compared by log-rank testing. Results A total of 189 patients were included. Sentinel lymph node detection significantly improved from 78.2% in the earlier cohort to 98.0% in the later cohort (p < 0.0001). Across the combined cohort, SLNB sensitivity was 72.5%, with a false-negative rate of 27.5%. False-negative events predominantly occurred in anatomically complex drainage regions. Sentinel lymph node status was not significantly associated with overall survival (p = 0.627). Conclusions Despite substantial improvements in detection rates, SLNB in head and neck melanoma demonstrates clinically relevant limitations in diagnostic sensitivity. The observed false-negative rate highlights a risk of understaging, which may affect eligibility for adjuvant systemic therapies. SLNB findings should therefore be interpreted in the context of anatomical risk patterns and integrated into individualized follow-up strategies. The lack of an association between sentinel lymph node status and overall survival may reflect the impact of modern adjuvant systemic therapies and the distinct biological behavior of head and neck melanoma. However, this finding should be interpreted with caution given the limited sample size. These findings underscore the importance of procedural expertise and risk-adapted surveillance in this anatomically complex region.

Background: Recurrent respiratory papillomatosis (RRP) is a rare, non-malignant disease caused by human papillomavirus (HPV) types 6 and 11. The condition primarily affects the larynx, potentially leading to life-threatening airway obstruction. It is more aggressive in younger patients, necessitating frequent surgical interventions. This study investigates the therapeutic potential of the prophylactic HPV vaccine Gardasil® in RRP patients, focusing on its impact on lesion size and the frequency of surgical interventions. Furthermore, a literature review was conducted to analyze the factors influencing the decision to vaccinate. Methods: A retrospective analysis was conducted on 63 RRP patients treated from 2008 to 2021. Disease burden was assessed using the Derkay score and the annual frequency of laser-surgical ablations. Comparisons were made between pre- and post-vaccination periods in vaccinated patients (n = 18), and between first and second halves of the disease’s course in unvaccinated patients (n = 14). Results: A reduction in the frequency of surgical interventions post-vaccination (p < 0.05) could be seen. The cumulated Derkay score per year decreased after second and third vaccination (p < 0.05). The decision to be vaccinated is influenced by multiple factors (e.g., potential side-effects, sociocultural factors, impact of social media, pre-existing conditions and the wider context of the recent pandemic). Conclusions: Gardasil® appears to reduce the frequency of surgery and lessen disease severity in RRP patients, supporting the potential role of HPV vaccination as a therapeutic option for RRP. Moreover, it is crucial to overcome skepticism towards vaccinations to prevent the development of HPV-associated diseases in the first place.

Einleitung Seit 2007 empfiehlt die ständige Impfkommission (STIKO) eine prophylaktische Impfung zur Verhinderung einer Infektion mit humanen Papillomviren (HPV). Ein möglicher therapeutischer Nutzen wird diskutiert. In dieser Untersuchung wird der Effekt der Impfung auf den Verlauf der rezidivierenden respiratorische Papillomatose (RRP) betrachtet.

Introduction Sentinel lymph node biopsy (SLNB) has been an integral part of the diagnosis and staging of malignant melanoma (MM) since the end of the last millennium. The indication for a sentinel lymph node biopsy is a tumor thickness of 1.0 mm or more in the absence of locoregional or distant metastases. A sentinel lymph node biopsy can also be performed in the case of a thinner primary tumor (0.75-1.0 mm) if there is an increased risk of occult lymph node metastases, e.g. in the case of an increased mitosis rate, young age or ulceration of the primary tumor. The positivity of a SLN has a significant influence on the subsequent therapy and prognosis. The aim of this retrospective analysis is, among other things, to determine the predictive value of the biopsy against the background of the actual course of the patient's disease. Of particular interest is the frequency of SLNs without metastasis in patients who nevertheless develop metastases in the course of the disease.

We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC). We analyzed digitized H E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses. TB was identified as an independent prognostic parameter, with TB-high cases showing inferior outcomes in univariate (HR: 3.08, 95

Purpose: The assessment of p16INK4a (p16) in oropharyngeal squamous cell carcinoma (OPSCC) has been incorporated into tumor classification, as p16 has been shown to impact survival probability. However, a recent study demonstrated that human papillomavirus (HPV) status in addition to p16 may have a better discriminatory effect on survival probability. This study aims to determine the impact of combined evaluation of p16 and HPV on prognosis. Methods: This was a multicenter, multinational analysis including retrospective and prospective cohorts of patients treated for primary OPSCC with curative intent, based on the data of the HNCIG-EPIC study. The primary outcome was to determine how the combined assessment of HPV and p16 status predicts prognosis of patients with OPSCC compared to p16 assessment alone. We employed multivariable analyses models to compute hazard ratios regarding survival. Analyses were stratified by stage, smoking status, and sub-anatomical region. = 3849). A total of 9.2 % of patients had discordant p16 and HPV status (n = 704). HPV status significantly impacted overall survival and disease-free survival regardless of p16 status and across both UICC 8th stage I-II Conclusion: The detection of HPV had a significant impact on survival probability for OPSCC patients with both

Introduction Subglottic stenoses (SGS) are constrictions in the region below the vocal folds, that can pose a life-threatening problem for those affected. The aim of this research project was to identify the patient group for which the treatment of SGS by balloon dilatation can lead to long-term success. Methods 14 patients with SGS were examined (before and up to12 months after intervention) using pulmonary function tests, laryngoscopies and two questionnaires (Clinical Chronic Obstructive Pulmonary Disease Questionnaire), (modified Medical Research Council Dyspnoea Scale) regarding the respiratory situation. Additionally, the number of necessary interventions, the degree of stenosis (according to Myer Cotton and measured in millimeters) were documented. Results Four patients who required only one intervention with the balloon showed better pre-interventional respiratory function and a higher subjective stress level. Lung function tests and evaluation of the questionnaires showed an improvement in the respiratory situation and state of health of all 14 patients after the initial intervention. The degree of stenosis measured in millimeters shows that patients with a stenosis diameter of less than 4 mm only required one intervention. All patients who received an intervention using a 12-mm-balloon had to be treated several times. Conclusions Patients with a high degree of stenosis and a tendency towards greater subjective stress and less objective restriction of the respiratory function appear to have a higher probability of long-term successful treatment with the balloon. Furthermore, the choice of balloon size seems to be an additional decisive factor for the success of an intervention.

Eine retrospektive Analyse von 357 PatientInnen (Pat.) mit einem Oropharynxkarzinom (OPKA) zeigte die unverändert positive Rolle der Chirurgie, auch bei den Frühstadien und dies unabhängig vom HPV-Status. Das krankheitsspezifische Überleben (KSÜ) war insgesamt besser als das Gesamtüberleben (GÜ) mit einem signifikanten Überlebensvorteil der HPV+. Gegenstand dieser Untersuchung ist, ob das ungünstigere GÜ im Vergleich zum KSÜ auf Alter, Komorbidität (KoMo), Nikotin und Alkohol zurückzuführen ist. Retrospektiv wurden die Daten von 357 OPKA-Pat. (249 m, 108 w, Alter Ø63,2 Jahre) aller Stadien untersucht, Rauchlast, Alkoholkonsum und KoMo erfasst und mit Therapie/-verlauf und HPV-Status in Bezug auf KSÜ und GÜ statistisch ausgewertet.134 (42%) haben KoMo, 141 (45,2%) rauchen aktiv, 23,4% nicht mehr und 31,4% nie; 52 (16,7%) trinken regelmäßig Alkohol,17% nicht mehr, 66,3% gelegentlich. KSÜ: HPV+überleben signifikant besser.Nicht- und Ex-Raucher ohne KoMo ebenfalls, mit KoMo überleben Nichtraucher besser als Ex- und aktive Raucher. Alkohol mit und ohne KoMo ist ohne Einfluss. Bezüglich GÜ überleben HPV+ohne KoMo am besten und HPV- mit KoMo am schlechtesten. Rauchen hebt den positiven Effekt von HPV auf; Alkohol ist ohne Einfluss. In der Gruppe OP+/- Adjuvans sind Nikotin, Alkohol und KoMo für das Überleben ohne Signifikanz. Dagegen ist bei der prim. RCT das KSÜ und GÜ der Nicht- und Ex-Raucher signifikant besser, während das der Pat. mit KoMo ungünstiger ist. Beim GÜ überleben die Nichtraucher am besten und Pat. mit KoMo signifikant schlechter. Alkohol ist ohne Einfluss auf KSÜ und GÜ. Die Ergebnisse unterstreichen den Einfluss von Rauchen und Komorbidität auf das Überleben, welcher sich signifikant negativ bei der primären RCT auswirkt. Dies sollte Berücksichtigung finden bei der Therapieempfehlung.

Zusammenfassung Einleitung Subglottische Stenosen (SGS) sind Verengungen im Bereich unterhalb der Stimmlippen, die ein lebensbedrohliches Problem für die Betroffenen darstellen können. Ziel dieses Forschungsprojektes war es, herauszufinden, bei welcher Patientengruppe die Behandlung der SGS mittels Ballondilatation zu einem längerfristigen Erfolg führen kann. Methoden 14 PatientInnen mit SGS wurden prospektiv (vor und bis zu 12 Monate nach Intervention) mittels Lungenfunktionstest, Laryngoskopien und zweier Fragebögen (Clinical Chronic Obstructive Pulmonary Disease Questionnaire), (modified Medical Research Council Dyspnoea Scale) zur Atemsituation untersucht. Zudem wurde die Anzahl der notwendigen Interventionen dokumentiert, der Stenosegrad gemessen und nach Myer Cotton bestimmt. Ergebnisse Vier PatientInnen, die nur eine Intervention mit dem Ballon benötigten, zeigten eine bessere präinterventionelle Atemfunktion sowie eine höhere subjektive Belastung. Mittels Lungenfunktionstests und der Auswertung der Fragebögen konnte eine Verbesserung der Atemsituation und des Gesundheitszustandes aller 14 PatientInnen nach der initialen Intervention nachgewiesen werden. PatientInnen mit einem Stenosedurchmesser unter 4 mm benötigten nur eine Intervention. ProbandInnen mit 12-mm-Ballon-Eingriffen benötigten wiederholt Behandlungen. Schlussfolgerungen ProbandInnen mit hohem Stenosegrad sowie tendenziell höherer subjektiver Belastung als auch geringerer objektiver Einschränkung der Atemsituation scheinen eine höhere Wahrscheinlichkeit für eine längerfristig erfolgreiche Behandlung mit dem Ballon zu haben. Die Wahl der Ballongröße scheint ein zusätzlich entscheidender Faktor für den Erfolg einer Intervention zu sein.

A retrospective analysis of 357 patients (pat.) with oropharyngeal carcinoma (OPCA) showed the unchanged positive role of surgery, even in the early stages and independent of HPV status. Disease-specific survival (DSS) was better than overall survival (OS) with a significant survival advantage of HPV+. The objective of this study is to determine whether the less favorable OS compared to DSS is due to age, comorbidity (CoMo), nicotine, or alcohol. Retrospectively, data from 357 OPCA pat. (249 m, 108 w, age Ø63.2 years) of all stages were examined, smoking behaviour, alcohol consumption, and CoMo were recorded, and statistically analyzed with therapy/progression and HPV status in relation to DSS and OS. 134 (42%) have CoMo, 141 (45,2%) actively smoke, 23,4% former, and 31,4% never smokers; 52 (16,7%) regularly drink alcohol, 17% no longer do. DSS: HPV+survive significantly better. Non- and ex-smokers without CoMo also; with CoMo nonsmokers survive better than ex- and active smokers. Alcohol consumption has no influence. Regarding OS, HPV+without CoMo survive best and HPV- with coMo survive worst. Smoking abrogates the positive effect of HPV; alcohol again has no influence. In the surgery+/- adjuvant group, nicotine, alcohol, and CoMo are without sgnificance for survival. In contrast, in the prim- RCT group DSS and OS of non- and ex-smokers is significantly better while that of patients with CoMo is less favorable. Regarding OS, non-smokers survive best and pat. with CoMo significantly worse. Alcohol has no influence.

Introduction Since 2007, the Standing Committee on Vaccination (STIKO) has recommended prophylactic vaccination to prevent human papillomavirus (HPV) infection. Possible therapeutic benefits are discussed. In this study, the effect of vaccination on the course of recurrent respiratory papillomatosis (RRP) is examined.

Die Wächterlymphknotenbiopsie (WLKB) stellt seit Ende des letzten Jahrtausends einen integralen Teil bei der Diagnosestellung und Bestimmung des Stadiums des malignen Melanoms (MM) dar. Die Indikation zur Wächterlymphknotenbiopsie besteht bei einer Tumordicke ab 1,0 mm und Abwesenheit von lokoregionären oder Fernmetastasen. Ebenfalls kann eine WLKB bei einem dünneren Primärtumor (0,75-1,0mm) durchgeführt werden, falls ein erhöhtes Risiko für okkulte Lymphknotenmetastasen besteht, z.B. bei einer erhöhten Mitoserate, jungem Alter oder Ulzeration des Primärtumors. Die Positivität eines WLK hat signifikanten Einfluss auf die weiterfolgende Therapie und Prognose. Das Ziel dieser retrospektiven Analyse ist unter anderem der prädiktive Wert der Biopsie vor dem Hintergrund des tatsächlichen Krankheitsverlaufs der PatientInnen zur ermitteln. Von besonderem Interesse ist hierbei die Häufigkeit von WLK ohne Metastasierung bei PatientInnen, welche im Verlauf aber doch Metastasen entwickeln. Hierzu werden die Daten von PatientenInnen, welche zwischen 2002 und 2020 in der HNO-Klinik des UKSH-Kiel behandelt worden sind, ausgewertet. Vorläufig konnten 117 Patientenverläufe retrospektiv ausgewertet werden. Die Detektionsrate der Wächterlymphknoten liegt bei 88,89% (111 von 117). Lokoregionäre Metastasen sind im Verlauf bei 5 von 81 Patienten mit initial negativem WLK aufgetreten (6,17%). Die Sensitivität liegt bei 85,71%. Die falsch-negativ Rate beträgt 16,67%. Der negativ-prädiktive Wert beträgt 94,7%. Die WLKB ist weiterhin ein wichtiger Bestandteil in der Diagnosestellung des malignen Melanoms im Kopf-Halsbereich. Den Behandelnden sollten jedoch die Limitationen des diagnostischen Verfahrens und die ggf. daraus resultierende unzureichende Therapie von PatientInnen bewusst sein.

The 44-year-old female patient presented with acute progressive swelling, redness, and pain of the nose without any previous illnesses and continuous medication. Oral antibiotic therapy under the suspected diagnosis of erysipelas was unsuccessful. In the course of time, the patient developed a recurrent conjunctivitis and a saddle nose. Laboratory chemistry revealed elevated CRP and ANA, and unremarkable ANCA and renal function. Coronary sinus CT, CT thorax and spirometry were unremarkable. Histopathologic examination of a tissue sample of the nasal mucosa, including review by a consultation and reference center for vasculitis diagnostics, resulted in a diagnosis of uncharacteristic rhinitis. Histopathologic workup of a biopsy of the auricle in the presence of unilateral perichondritis that occurred during the course revealed evidence of relapsing polychondritis. After an interdisciplinary workup of the findings in the Center of Excellence for Inflammation Medicine of the UKSH, the patient was treated with methotrexate (15 mg 1x per week), folic acid (10 mg) and cortisone (the starting dose was 100 mg). In the absence of improvement of the symptoms, off label therapy with a humanized monoclonal Il-6 receptor antibody (Tocilizumab 163 mg 1x per week) was successfully initiated. Relapsing polychondritis is a rare disease. Diagnosis is usually difficult and various differential diagnoses must be excluded. In an untreated state, the course is destructive and possibly life-threatening (tracheal manifestation). No uniform standards have been described for immunomodulatory therapy. Agents specifically affecting the inflammatory metabolic pathways represent promising new therapeutic options.

Carbapenemase-producing bacteria (CPB) such as Klebsiella pneumoniae and Escherichia coli are causing hospital outbreaks worldwide. An important transfer route into the aquatic environment is the urban water cycle. We aimed to determine the presence of CPB in hospital wastewater, wastewater treatment plants (WWTPs) and surface waters in a German metropolitan area and to characterise these bacteria by whole-genome comparisons. During two periods in 2020, 366 samples were collected and cultivated on chromogenic screening media. Bacterial colonies were selected for species identification and PCR-based carbapenemase gene screening. Genomes of all detected CPB were sequenced and analysed for resistance gene content, followed by multilocus sequence typing (MLST) and core genome MLST (cgMLST) for K. pneumoniae and E. coli isolates. Carbapenemase genes were detected in 243 isolates, most of which belonged to genera/species Citrobacter spp. (n = 70), Klebsiella spp. (n = 57), Enterobacter spp. (n = 52) and E. coli (n = 42). Genes encoding KPC-2 carbapenemase were detected in 124 of 243 isolates. K. pneumoniae produced mainly KPC-2 and OXA-232 whereas E. coli harboured various enzymes (KPC-2, VIM-1, OXA-48, NDM-5, KPC-2 + OXA-232, GES-5, GES-5 + VIM-1, IMP-8 + OXA-48). Eight and twelve sequence types (STs) were identified for K. pneumoniae and E. coli, respectively, forming different clusters. The detection of numerous CPB species in hospital wastewater, WWTPs and river water is of concern. Genome data highlight a hospital-specific presence of distinct carbapenemase-producing K. pneumoniae and E. coli strains belonging to "global epidemic clones" in wastewater samples representing local epidemiology. The various detected CPB species including E. coli ST635, which is not known to cause human infections, could serve as reservoirs/vectors for the spread of carbapenemase genes in the environment. Therefore, effective pretreatment of hospital wastewater prior to discharge into the municipal wastewater system may be required, although swimming lakes do not appear to be a relevant risk factor for CPB ingestion and infection.

Das Oropharynxkarzinom (OPKA) wird aufgrund steigender Inzidenz, besseren überlebens der HPV-positiven mit deren Downstaging in der 8. TNM-Klassifikation und der Ergebnisse der ORATOR-Studie mit besserem Behandlungsergebnis primärer Radiochemotherapie (RCT) intensiv diskutiert. In dieser retrospektiven Analyse haben wir das Gesamt- und tumorspezifische überleben (Gü,TSü) von 357 PatientInnen (249 männl., 108 weibl., Alter Ø 63,18 Jahre), die von 2013 bis 2020 wegen eines nicht vorbehandelten OPKA aller Stadien (8. TNM) therapiert wurden, untersucht und nach Therapieart und HPV-Status verglichen. Medianes follow-up 34,68 Monate, 162/357 (45,5%) Früh-(I/II), 194/357 (54,4%) fortgeschrittenes (III/IV) Tumorstadium; 127/357 HPV-positiv (142/357 p16-positiv) und 68/357 HPV-negativ. Therapie: 20,4% (73/357) OP, 47,9% (171/357) OP+RCT, 31,7% (113/357) primäre RCT. Das 5-Jahres-Gü betrug 77,6% (HPV+ 88%, HPV- 57,5%), I/II 89,6%, III/IV 69,1%. Das 5-Jahres-TSü betrug 83,3% (HPV+ 90,4%, HPV- 67,7%), I/II 94,5%, III/IV 75,1%. Es zeigte sich OP+RCT beim TSü in allen Stadien überlegen, beim Gü bestand nur im Stadium III/IV bei der OP+RCT-Gruppe ein signifikanter überlebensvorteil zur pRCT. Stratifiziert nach HPV-Status zeigte sich beim TSü kein Unterschied nach pRCT, aber ein signifikant besseres überleben bei OP+RCT bei HPV+ im Vergleich zur pRCT; kein Unterschied bestand zwischen OP und OP+RCT. Beim HPV- OPKA war das überleben nach OP signifikant besser als nach OP+RCT, zwischen OP+RCT und pRCT bestand kein Unterschied. Die Ergebnisse dieser retrospektiven Studie (n=357, I/II n=162) unterstützen die Ergebnisse der prospektiven ORATOR-Studie (n=61) nicht und betonen die Rolle der Chirurgie selbst für HPV+OPKA. Der Einfluss von Komorbidität und Rauchstatus wird derzeit ausgewertet.