[Eosinophils in otorhinolaryngology: friend or foe?] / Eosinophile in der HNO-Heilkunde: Freund oder Feind?

This article summarizes the essential aspects of current knowledge about eosinophils, classifies eosinophilia in terms of the dimensions healthy or harmful reaction, takes a specific look at eosinophils in the field of otorhinolaryngology, and gives recommendations for diagnostic workup and therapeutic intervention in case of proven eosinophilia, particularly as an adverse drug reaction. The thoughts are inspired by communications at the 29th Congress of the European Rhinologic Society in Sofia, Bulgaria, 2023.

EGPA: Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) as a special presentation of chronic rhinosinusitis with nasal polyps (CRSwNP).

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) was formerly known as Churg-Strauss syndrome. The condition is characterized by disseminated necrotizing vasculitis with extravascular granulomas associated with hypereosinophilia. The vasculitides affect small vessels and are associated with antineutrophil cytoplasmic antibodies (ANCAs) detectable in the blood. Distinguishing between type 2-mediated chronic airway inflammation such as chronic rhinosinusitis with nasal polyps (CRSwNP) without vasculitis can be clinically challenging and should be considered. MATERIALS AND METHODS: Immunological background, diagnosis, and therapy of EGPA were identified through literature searches in Medline, PubMed, as well as national and international studies (ClinicalTrials.gov) and the Cochrane Library. Human studies published up to and including 10/2023 on the topic were considered. RESULTS: In cases of deteriorating general health with previously known eosinophilic inflammation of the upper and lower airways, EGPA and its interdisciplinary investigation should be considered. Various types of eosinophilic inflammation and syndromes must be considered differentially. CONCLUSION: Characterization of mucosal airway inflammation through biomarker determination is meaningful and occasionally makes the difference for targeted therapy.

Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

[Fundamentals and practice of the application of nasal packing in sinonasal surgery]. / Grundlagen und Praxis der Anwendung von Nasentamponaden in der endonasalen Chirurgie.

BACKGROUND AND OBJECTIVES: This paper presents an overview on nasal packing materials which are available in Germany. The current literature is analyzed whether there are robust criteria regarding use nasal packing after sinonasal surgery, whether there are fundamental and proven advantages or disadvantages of products, and what this means in clinical practice. MATERIALS AND METHODS: Selective literature analysis using the PubMed database (key words "nasal packing", "nasal tamponade", "nasal surgery", "sinonasal surgery", or "sinus surgery"), corresponding text books and resulting secondary literature. RESULTS AND CONCLUSIONS: Because of systematic methodological shortcomings, the literature does not help in the decision-making about which nasal packing should be used after which kind of sinonasal surgery. In fact, individual approaches for the many different clinical scenarios are recommended. In principle, nasal packing aims in hemostasis, should promote wound healing, and should not result in secondary morbidity. Nasal packing materials should be smooth (non-absorbable materials), inert (absorbable materials), and should not exert excessive pressure. Using non-absorbable packing entails the risk of potentially lethal aspiration and ingestion. For safety reasons inpatient control is recommended as long as this packing is in situ. With other, uncritical packing materials and in patients with special conditions, outpatient control could be justified.

A technical feasibility study on adaptation of a microsurgical robotic system to an intraoperative complication management in dental implantology: perforated Schneiderian membrane repair using Symani® Surgical System.

The aim of the current study was to test the technical and clinical feasibility of a robotic system and investigate its potential in the surgical repair of perforated Schneiderian membranes using an ex-vivo porcine model. Eight pig heads were operated conventionally via a surgical loop and eight pig heads with the surgical robot "Symani® Surgical System" (Medical Microinstruments, Inc., Pisa, Italy). On each specimen, the Schneiderian membrane was incised over a length of 0.7 mm resembling a perforation. Operation time, the maximum sinusoidal pressure, the course of the pressure and the filling volume were measured. Additionally, adaptation of the wound edges has been detected via scanning electron microscopy. There were no significant differences for the pressure maximum (p = 0.528), for the time until the pressure maximum was reached (p = 0.528), or for the maximum filling volume (p = 0.674). The time needed for the suturing of the membrane via robotic surgery was significantly longer (p < 0.001). However, the scanning electron microscope revealed a better adaptation of the wound edges with robotic surgery. The technical feasibility of robot-assisted suturing of Schneiderian membrane laceration using the robotic system has been confirmed for the first time. No differences considering the pressure resistance compared to the conventional repair could be observed, but advantages in wound adaptation could be found with an electron microscope. Regarding the material and training costs and limited indications spectrum, robotic surgery systems still might not present financially feasible options in the daily dental practice yet.

[Treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with monoclonal antibodies (biologics): S2k guideline of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the German College of General Practitioners and Family Physicians (DEGAM)]. / Therapie der chronischen Rhinosinusitis mit Polyposis nasi (CRScNP) mit monoklonalen Antikörpern (Biologika): S2k-Leitlinie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) und der Deutschen Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM).

Monoclonal antibodies (so-called biologics) can be prescribed for chronic rhinosinusitis with nasal polyps (CRSwNP) within the scope of their market authorization. However, their prescription is limited to severe CRSwNP without disease control, whereby certain requirements must be met. Dupilumab, omalizumab, and mepolizumab have currently gained market authorization, with adequate evidence for their efficacy and safety available in the literature. It can be assumed that other biologics will be approved for this indication in the future. The severity of disease and the efficacy of treatment should be assessed objectively and subjectively before treatment initiation and after an appropriate duration, respectively. The documentation sheet proposed in this guideline chapter can be used for the assessments. In the presence of relative contraindications, a treatment should only be initiated after differentiated consideration by an experienced physician in the sense of a case-by-case decision. In summary, this guideline chapter aims to contribute to high-quality care of adult patients with these therapies in view of the increasing evidence for treatment with these substances and the increasing number of market authorizations of different biologics.

Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study.

Background: Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS. Methods: COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742). Findings: In Kiel-I (n = 667, 57% women), 90% of participants had received outpatient treatment for acute COVID-19. Neurological ailments (61·5%), fatigue (57·1%), and sleep disturbance (57·0%) were the most frequent persisting symptoms at 6-12 months after infection. Across sub-cohorts (Würzburg/Berlin, n = 316, 52% women; Kiel-II, n = 459, 56% women), higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index: r = -0·54/ -0·56, all p < 0·0001). Severe, moderate, and mild/no PCS according to the individual participant's PCS score occurred in 18·8%, 48·2%, and 32·9%, respectively, of the Kiel-I sub-cohort. In both validation sub-cohorts, statistically significant predictors of the PCS score included the intensity of acute phase symptoms and the level of personal resilience. Interpretation: PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions. Funding: The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON).

Tonsillar swabs and sputum predict SLPI- and AnxA2 expression in tonsils: A prospective study on smoking dependent SLPI- and AnxA2-expression, and tonsillar HPV infection.

Previous retrospective studies have elucidated a correlation between secretory leucocyte protease inhibitor (SLPI) and Annexin A2 (AnxA2), patient smoking status and tonsillar human papilloma virus (HPV) status. The current study assessed these parameters prospectively and to the best of our knowledge, analyzed SLPI-/AnxA2-expression for the first time in tonsillar swabs and sputum. Samples were obtained from 52 patients with tonsillar squamous cell carcinoma and 163 patients with tonsillar hyperplasia (H; n=56) and chronic or recurrent tonsillitis (CRT; n=107). HPV-DNA, SLPI and AnxA2 gene expression was analyzed in sputum, tonsillar swabs and tissue by performing reverse transcription-quantitative PCR. Results were compared with smoking status, revealing that smoking resulted in significantly increased SLPI gene expression in all biomaterials of all cases. SLPI-gene expression was significantly decreased in all HPV-DNA-positive samples (tissue/swab/sputum), while AnxA2 was significantly increased in all HPV-DNA-positive samples. Results from swabs and sputum were able to predict SLPI- and AnxA2 gene expression of the corresponding tonsil. The current prospective study confirmed previous retrospective results underlining this hypothesis: Smoking enhances SLPI-expression, preventing HPV-binding to AnxA2. HPV-binding to AnxA2 appears essential for successful cell-entry. SLPI/AnxA2-gene expression in swabs and sputum reflect their expression in tonsillar tissue. Accordingly, a positive AnxA2/SLPI-ratio in sputum/swabs could possibly be used to reduce HPV-associated carcinogenesis, by performing tonsillectomy or HPV-vaccination in patients with positive AnxA2/SLPI-ratios.

[The impact of smoking habit alteration on prognosis of head and neck cancer patients]. / Eine Änderung des Rauchverhaltens beeinflusst das Überleben von HNSCC-Patienten.

INTRODUCTION: The influence of smoking on survival in patients with HNSCC is well documented in the literature. There is little data on changes in smoking habits after diagnosis. Here, the effect on survival of the reduction of smoking compared to full smoking cessation is investigated. PATIENTS AND METHODS: Patient records and tumor documentation of 643 consecutive HNSCC cases of the Head and Neck Tumor Center of the University Hospital Kiel are evaluated retrospectively: smoking habits before and after treatment and survival are evaluated. RESULTS: Change in smoking behavior at the initial diagnosis of HNSCC leads to a significant positive effect on the prognosis compared to continued smoking. There is no difference between smoke reduction and weaning. This effect is based solely on those patients who are treated exclusively by surgery. Lifelong non-smokers have a significant survival advantage over active and ex-smokers, with no difference between the latter two groups. CONCLUSIONS: The positive influence of changed smoking habits on the prognosis runs parallel to the negative direct effect of active smoking on therapy, which is attributed to peritumoral hypoxia with a negative effect on the effectiveness of R(C)T. The positive effect of the change in smoking behaviour during surgery alone is most likely due to reduced peri-operative complications. Patients should be encouraged to at least minimize smoking with the cancer diagnosis. In addition, former smokers should be considered active smokers for survival estimates and therapy planning.

[Smoking and co-morbidity - it's impact on dose achievement in radio(chemo)therapy for HNSCC]. / Rauchen und Komorbidität ohne Einfluss auf geplante Zieldosis der Radio(chemo)therapie.

Smoking worsens the prognosis of patients with HNSCC. Furthermore, smoking is associated with the prevalence of co- and multimorbidity, so that it is assumed that not smoking per se, but co-/multimorbidity worsens the prognosis due to lack of compliance to therapy, e. g. by reducing the dose of the planned radio(chemo)therapy (RCT). However, data on this topic are currently sparse and contradictory, especially for HNSCC.Patient records and tumor documentation of 643 consecutive cases of the Head and Neck Tumor Center of the University Hospital Kiel were retrospectively evaluated. Patient characteristics and smoking habits were recorded and correlated with co-/multimorbidity and treatment course.The 643 patient files examined show that 113 (17.6 %) patients did not smoke, 349 (54.3 %) were active and 180 (28 %) patients had previously smoked. 315 (49 %) are treated exclusively by surgery; 121 (18.8 %) by surgery + adjuvant RCT and 72 (11.2 %) by surgery + adjuvant RT. 111 (17.3 %) receive a primary RCT and 24 (3.7 %) a primary RT. 131 (20.4 %) show co-/multimorbidity and 512 (79.6 %) do not. Smoking (> 10 py) is significantly associated with comorbidity (p = 0.002). However, smoking and comorbidity, neither alone nor in combination, are correlated with the achievement of the target dose of RCT (p > 0.05).As expected, smoking is significantly linked to co-/multimorbidity. Dose reduction of R(C)T is just as frequent in active smokers and patients with co-/multimorbidity as in non-smokers and patients without co-/multimorbidity. Thus, smoking and co-/multimorbidity influence the prognosis in other ways than by interfering with planned therapy regimens.

Comparison of Clinical Examination and Various Imaging Modalities in the Diagnosis of Head and Neck Cancer.

Introduction Squamous cell Carcinoma of the Head and Neck (HNSCC) is the most common tumor entity of malignant processes in the head and neck area. Due to the metastasizing behavior of these tumors, the staging is indispensable for the treatment planning and requires imaging techniques, which are sensitive, specific, and as far as possible cost-effective, to benefit ultimately the patient and to ensure optimal care. Objectives The aim of the present study is to compare the clinical examination including palpation, ultrasound and computed tomography (CT)/magnetic resonance imaging (MRI) for the diagnosis of neck metastases to make the correct indication for a neck dissection. Methods Data from 286 patients with HNSCC were analyzed for neck metastases to determine which diagnostic tool is the best to answer the question if a neck dissection is necessary or not. Each study method was examined retrospectively by comparing sensitivity, specificity, the positive/negative predictive value, the positive likelihood ratio and the diagnostic accuracy. Results The ultrasound showed a sensitivity of 91.52%, a specificity of 61.67%, a positive/negative predictive value of 76.65%/84.09%, a positive likelihood ratio of 2.39 and a diagnostic accuracy of 78.95%. The clinical examination showed a sensitivity of 75.76%, a specificity of 66.12%, a positive/negative predictive value of 75.30%/66.67%, a positive likelihood ratio of 2.24 and a diagnostic accuracy of 71.68%. The CT/MRI showed a sensitivity of 78.66%, a specificity of 62.50%, a positive/negative predictive value of 74.14%/68.18%, a positive likelihood ratio of 2.10 and a diagnostic accuracy of 71.83%. Radiographically, ultrasound, as well as the clinical examination, could be judged to be free from radiation load and side effects from the contrast medium. The high dependence on the investigator when using ultrasound made reproducibility of the results difficult. Conclusions It could be shown that ultrasound was the diagnostic tool with the highest sensitivity, positive/negative predictive value, positive likelihood ratio and diagnostic accuracy by detecting and interpreting metastases in the head and neck region correctly. Whether a neck dissection should be performed depends to a large extent on the ultrasound findings.

Comparison of Clinical Examination and Various Imaging Modalities in the Diagnosis of Head and Neck Cancer

Abstract Introduction Squamous cell Carcinoma of the Head and Neck (HNSCC) is the most common tumor entity of malignant processes in the head and neck area. Due to the metastasizing behavior of these tumors, the staging is indispensable for the treatment planning and requires imaging techniques, which are sensitive, specific, and as far as possible cost-effective, to benefit ultimately the patient and to ensure optimal care. Objectives The aim of the present study is to compare the clinical examination including palpation, ultrasound and computed tomography (CT)/magnetic resonance imaging (MRI) for the diagnosis of neck metastases to make the correct indication for a neck dissection. Methods Data from 286 patients with HNSCC were analyzed for neck metastases to determine which diagnostic tool is the best to answer the question if a neck dissection is necessary or not. Each study method was examined retrospectively by comparing sensitivity, specificity, the positive/negative predictive value, the positive likelihood ratio and the diagnostic accuracy. Results The ultrasound showed a sensitivity of 91.52%, a specificity of 61.67%, a positive/negative predictive value of 76.65%/84.09%, a positive likelihood ratio of 2.39 and a diagnostic accuracy of 78.95%. The clinical examination showed a sensitivity of 75.76%, a specificity of 66.12%, a positive/negative predictive value of 75.30%/66.67%, a positive likelihood ratio of 2.24 and a diagnostic accuracy of 71.68%. The CT/MRI showed a sensitivity of 78.66%, a specificity of 62.50%, a positive/negative predictive value of 74.14%/68.18%, a positive likelihood ratio of 2.10 and a diagnostic accuracy of 71.83%. Radiographically, ultrasound, as well as the clinical examination, could be judged to be free from radiation load and side effects from the contrast medium. The high dependence on the investigator when using ultrasound made reproducibility of the results difficult. Conclusions It could be shown that ultrasound was the diagnostic tool with the highest sensitivity, positive/negative predictive value, positive likelihood ratio and diagnostic accuracy by detecting and interpreting metastases in the head and neck region correctly. Whether a neck dissection should be performed depends to a large extent on the ultrasound findings.

The interaction of smoking habit, SLPI and AnxA2 in HPV associated head and neck and other cancers.

Six own studies confirm a correlation between smoking, expression of the secretory leukocyte protease inhibitor (SLPI, an antileukoproteinase) and expression of Annexin A2 (AnxA2), and their influence on human papilloma virus (HPV)-infections. SLPI and HPV are ligands of AnxA2. This correlation was tested on 928 tissue samples from 892 patients in six independent studies [squamous cell carcinoma of the head and neck (HNSCC), n = 522; non-neoplastic tonsils n = 214; clinically normal mucosa, n = 93 (of these n = 57 were obtained from patients treated for non-malignant diseases and n = 36 were obtained from HNSCC-patients) and vulvar squamous cell carcinoma (VSCC) n = 99]. HPV-DNA-status was determined by GP5+/GP6+-PCR, followed in case of HPV-positivity by Sanger sequencing and RT-PCR using HPV-type specific primers. SLPI- and AnxA2-gene-expression was determined by RT-q-PCR; SLPI-protein-expression was additionally determined by immunohistochemistry (IHC); the data were correlated with each other and with patient characteristics. Smoking results in increased SLPI-gene- and protein- and AnxA2-gene-expression with significantly higher SLPI- than AnxA2-gene-expression. SLPI is decreased in non-smokers with a continuous AnxA2-surplus. HPV-status correlates with smoking habit, with smokers being mostly HPV-negative and non-smokers HPV-positive. We hypothesize that smoking leads to SLPI-overexpression with SLPI-binding to AnxA2. Thus, HPV cannot bind to AnxA2 but this seems pivotal for HPV-cell-entry. Smoking favors SLPI-expression resulting in HPV-negative carcinomas, while HPV-positive carcinomas are more common in non-smokers possibly due to a surplus of unbound AnxA2. In addition, the hypothesis may contribute to understand why smokers show increased oral HPV-prevalence in natural history studies but do not necessarily develop HPV-associated lesions.

HPV DNA/RNA detection in various oral and oropharyngeal biomaterials identifies active HPV infections also in non-neoplastic tonsils.

Previous studies describe a correlation between HPV-positivity and non-smoking in TSCC; p16INK4A-expression as surrogate-marker for HPV-DNA/RNA-positivity is discussed controversially. In the present study, these parameters are assessed prospectively. HPV-status of sputum and tonsillar-swabs was analyzed to determine their validity as surrogate-marker for tissue-HPV-status. TSCC- (n = 52) and non-neoplastic tonsillar tissue (n = 163) were analyzed. HPV-DNA- and HPV-RNA-status of total sputum, cellular fraction and supernatants, tonsillar-swabs and -tissue was determined by (RT)-PCR. Immunohistochemistry determined p16INK4A-expression. 23/163 (14.2%) non-neoplastic tonsils were HPV-DNA-positive; five patients (3 HPV16, 2 HPV11) had active HPV-infections (HPV-RNA-positive), in all biomaterials. 140/163 (85.9%) patients were either HPV-DNA-positive or HPV-DNA-negative in all samples. 21/52 (40.4%) TSCC-tonsils were HPV-DNA-positive; 17 patients were HPV-RNA-positive (14 HPV16; 4 HPV18). 40/52 (76.9%) TSCC-patients were congruent in all biomaterials. p16INK4A-expression alone would have misclassified the HPV-status of 14/52 (26.2%) TSCC-patients. This prospective study confirms the discrepancy between HPV-status and p16INK4A-expression and the significant correlation between non-smoking and HPV-DNA-positivity. HPV-sputum- and/or swab-results do not consistently match tissue-results, possibly having (detrimental) consequences if those were used to assess tissue-HPV-status. In the 5 patients with active HPV infection in the non-neoplasitic tonsils, tonsillectomy likely prevented subsequent development of TSCC.

Success of minimally invasive salivary gland surgery-Quality of life, prognostic factors.

OBJECTIVE: Goal of this study was to investigate, whether sialendoscopy in obstructive salivary gland disorders affects patients' oral health-related quality of life compared to healthy individuals, and to determine factors that might influence this relationship. STUDY DESIGN: Retrospective observational study. SETTING: University of Kiel, Department of Otorhinolaryngology, Head and Neck Surgery. SUBJECTS AND METHODS: A group of 130 patients, undergoing sialendoscopy between 01/2004 and 06/2017 was considered. Oral health-related quality of life was assessed using the OHIP-G14 (Oral Health Impact Profile) in combination with a custom-made questionnaire on satisfaction and success in relation to sialendoscopy. RESULTS: Oral health-related quality of life of patients without dentures or with removable dentures was significantly worse than in the healthy population, whereas the necessity of multiple additional follow-up treatments was associated with worse oral health-related quality of life. No essential predisposing factors were identified. Average satisfaction with the intervention was observed to be x̅ = 4.33 (SD = 3.69) on a visual analogue scale from 1 (=very satisfied) to 10 (=very unsatisfied). A longer follow-up period and a higher patients' age were positively related, whereas removal of salivary gland during follow-up was negatively related to satisfaction. In 113 cases (86.9%) long-term preservation was accomplished and 115 (88.5%) patients would repeat a sialendoscopy in case needed. CONCLUSION: In summary, sialendoscopy resulted in long-term high subjective and objective success rates. However, oral health-related quality of life scores did not reach those levels found in the healthy population.

No association between HPV-status in tonsillar tissue and sexual behavior of the patients in a northern German population - Critical view of the link between HPV natural history and HPV-driven carcinogenesis.

HPV-infection in patients with HNSCC is reportedly correlated with sexual behavior, age, and tobacco/alcohol-consumption. HPV-infections of the oral cavity are regarded as sexually transmitted. Comparable data of patient populations outside the U.S. are sparse or missing. Questionnaires regarding sexual behavior, education tobacco- and alcohol-consumption, were given to 28 patients with tonsillar hyperplasia (H) and 128 patients with tonsillar carcinomas (CA), all with tissue-typed HPV-DNA-status performing PCR. Answers were correlated among groups and HPV-status. 106 questionnaires were analyzed. Comparisons between H- (n = 25) and CA- (n = 81) patients showed that CA-patients were older (61.1yrs ± 9.3) than H-patients (45.2yrs ± 11.9; p < 0.0001; Student's t-test); had a lower educational level (p = 0.0095); and lower number of sexual partners (p = 0.0222; Fisher's exact test). All groups showed a significant correlation between smoking and lack of HPV-DNA-positivity (p = 0.001). Further Fisher's exact tests and logistic regression analysis revealed in all 106 patients no significant correlations between tissue-HPV-status and the analyzed parameters. Despite the limited sample size, we were able to confirm the established correlation between smoking and tissue-HPV-status. The correlation between sexual behavior and HPV-infection was not confirmed. No consensus exists in the literature about the latter. Our data does not support the strict classification of oral HPV-infections and HPV-driven HNSCCs as STDs.

Alteration of smoking habit at time of first diagnosis influences survival of patients with HNSCC.

The impact of smoking on survival in patients with squamous cell carcinoma of the head and neck is well established, despite some conflicting data in the literature. However, data on alterations of smoking habit following cancer diagnosis is sparse. In the present study, the effect of reduction of smoking compared with cessation on the course of disease was studied. Data from 643 patients with HNSCC from the tumor documentation registry of the Department of Otorhinolaryngology, Head and Neck Surgery of the Christian-Albrechts-University Kiel were collected and statistically analyzed, looking at pre- and post-treatment smoking habit and survival. Alteration of smoking at the first diagnosis of HNSCC led to a significantly beneficial effect on survival outcomes compared with continued smoking, without significant differences between reduction and cessation of smoking. Detailed analysis revealed that this effect was solely dependent on patients treated by surgery only. Lifelong non-smokers exhibited a significant survival advantage compared with active and former smokers, with no difference in survival between these last two groups. The positive influence of altered smoking habit following first time diagnosis on disease-specific survival paralleled the negative direct effect of active smoking on therapy, which is predominantly attributed to peritumoral tissue hypoxia leading to impaired efficacy of radiochemotherapy (RCT). In the present study cohort, the positive effect of smoking habit alterations were primarily observed in patients treated by surgery only instead of RCT, possibly due to fewer perioperative complications. These findings indicated that patients should be encouraged to at least minimize smoking following cancer diagnosis. Furthermore, for survival estimates and therapy planning, former smokers should be considered as active smokers.

The Influence of Smoking and Co-morbidity on Dose Achievement in Primary or Adjuvant Radio(Chemo)Therapy in Head and Neck Squamous Cell Carcinoma (HNSCC).

Introduction: Smoking has a negative impact on survival of HNSCC patients. In addition, smoking is associated with the prevalence of co-morbidities and, thus, it may be assumed that not smoking per se but co-morbidities impact the course of therapy in terms of lower compliance and dose-reduction. However, data addressing this issue is sparse and conflicting at present, specifically for HNSCCs. Patients and methods: Patient files and tumor documentation from 643 consecutive cases of the University Head and Neck Cancer Centre Kiel were analyzed retrospectively. Patient characteristics and smoking habits were assessed and correlated with co-morbidities and course of treatment. Results: The examined 643 patient files showed that 113 (17.6%), 349 (54.3%), and 180 (28%) patients were never, active, and former smokers, respectively. Three hundred fifteen (49%) were treated by surgery only; 121 (18.8%) received surgery + adjuvant RCT and 72 (11.2%) surgery + adjuvant RT. 111 (17.3%) received primary RCT and 24 (3.7%) primary RT. 131 (20.4%) and 512 (79.6%) had no or had co-morbidities, respectively. Smoking (>10 py) was significantly associated with co-morbidities (p = 0.002). However, smoking and co-morbidities, neither alone nor in combination, were correlated with failure in reaching target doses of radio(chemo)therapy (p > 0.05). Applying (verified) Carlson-Comorbidity-Index (CCI) did not change the results. Conclusions: As expected, smoking is significantly associated with co-morbidities. Dose-reduction of radio(chemo)therapy is as common among active smokers and patients with co-morbidities as among never smokers and patients without co-morbidities. Thus, smoking and co-morbidity seems to impact survival by other means than impairing planned therapy regimens.