[Recurrent laryngeal papillomatosis]. / Rezidivierende Larynxpapillomatose.

Human papillomaviruses (HPV) 6 and 11 cause 90% of recurrent laryngeal papillomatosis (RLP). It is unclear whether recurrences are caused by new infections or the spread of infected cells. Symptomatic and sometimes curative treatment is laser surgery or conventional microsurgical removal. RLP surgery aims to relieve shortness of breath and improve the voice. Patients (especially children) are affected by voice problems, repetitive surgeries, pulmonary manifestations, and psychological trauma. Vaccination with Gardasil 9 (Merck & Co., Rahway, NJ, USA) prevents new infections with HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 and induces vaccine antigen-specific antibodies and CD4+ T helper cells. According to current studies, RLP can be avoided with prophylactic vaccination. The treatment is associated with a general vaccination risk (European Medicines Agency approval: girls and boys from 9 years). Studies also show that the vaccine after removal of HPV-associated neoplasia/papilloma prevents recurrences. Extension of the vaccination recommendation to prevent recurrences of HPV-associated diseases in men may promote applicability and herd immunity. For rare and treatment-refractory cases with laryngotracheal involvement, systemic therapy with bevacizumab (e.g. Avastin; Genentech, San Francisco, CA, USA), a VEGF antibody, is a promising adjuvant treatment option.

[Contemporary use of instruments during clinical examination in German ENT departments and private practices]. / Einsatz von Instrumenten bei der klinischen Untersuchung in deutschen HNO-Abteilungen und Privatpraxen heutzutage.

BACKGROUND: The classical forehead reflector as traditionally used by ear, nose, and throat (ENT) physicians for the ENT examination is now iconic for doctors in general. It is unknown which instruments are currently used in Germany to clinically examine ENT patients. Therefore, this study aims to present results of a survey about commonly used instruments. MATERIALS AND METHODS: An evaluation of 321 questionnaires from ENT doctors working in general and university hospitals (172) and in private practices (149) was performed. RESULTS: The ENT mirror examination is nowadays carried out with a self-illuminating headlamp with battery and/or light guide cable. Approximately 20% of respondents also use a forehead mirror. The microscope is used by 90% of doctors to examine the ears; a rigid endoscope was used in 53.3% to examine the larynx, epipharynx (41.1%), and the nose/sinuses (34.6%). Flexible endoscopes and otoscopes are used only rarely. CONCLUSION: The self-illuminating headlamp, which is more often wireless in eastern Germany, has largely replaced the classical forehead reflector, with which doctors younger than 40 years were no longer trained. At least some organs are also examined very regularly with the microscope or rigid endoscope. The flexible endoscope and otoscope are used much less frequently overall, mainly by younger physicians and ENT doctors working in hospitals. The diagnostic potential of flexible endoscopy may be compromised by the outpatient remuneration structures in Germany.

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients.

PURPOSE: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. METHODS: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). RESULTS: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm3, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. CONCLUSIONS: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.

[Altered indication for parotidectomy in north-western Brandenburg: A longitudinal study]. / Veränderte Indikation zur Parotidektomie im nordwestlichen Brandenburg: Eine Longitudinaluntersuchung.

OBJECTIVE: Knowledge about parotoidectomy indications is based on notifications to ENT departments and tumor databases. The study investigates the hypothesis that the surgical indication for parotoidectomy has changed over recent years. MATERIAL AND METHODS: We performed a retrospective observation study of patients who underwent parotidectomy between 1975 and 2016 (subdivided into 4 quartiles) in a teaching hospital of a medical university. RESULTS: 405 men and 366 women underwent operation for benign tumors (600/78 %), malignant tumors (116/15 %) or parotitis (55/7 %). The proportion of benign tumors remained unchanged (78 %), whereas malignant tumors increased (7 % - 23 %) and parotitides decreased (17 % - < 1 %). In benign tumors, the proportion of pleomorphic adenomas decreased (60 % - 24 %), whereas Warthin tumors increased (23 % - 58 %). Among malignant tumors, the proportion of metastases increased from 2/13 to 31/49 (in particular squamous cell carcinomas of the skin). CONCLUSIONS: The present the study shows the decreasing importance of parotitis as an indication for parotidectomy due to improved non-surgical procedures. The increasing prevalence of Warthin tumors was associated with an increasing proportion of smokers. Increased number of malignant tumors was caused by an increased prevalence of intraparotidial matastases of cutaneous squamous cell carcinoma. The presented results are based on the evaluation of patient charts. Due to their ICD or DRG reference, histological findings cannot be generated by evaluating databases. For this purpose, a special salivary gland tumor database should be established.

[Immunotherapy Against Head and Neck Cancer Stem Cells]. / Immuntherapie gegen Tumorstammzellen bei Plattenepithelkarzinomen im Kopf-Hals-Bereich.

Immunotherapy against head and neck cancer stem cells Immunologic therapies like antibodies in solid tumors like squamous cell cancer of the head and neck are administered either alone or in combination with radiation and chemotherapy. Despite some respectable successes, the effect of this therapy reaches its limits due the ability of the tumor to escape the immune system. Cancer stem cells seem to play an important role in this process due to their intrinsic resistance to conventional therapy and the ability to regenerate tumor heterogeneity. This way they substantially contribute to the formation of recurrences and metastases. Therefore, future immunotherapies should target specifically this subpopulation, possibly in combination with other therapeutic modalities. In this review the immunologic features of cancer stem cells and their potential as target for immunotherapies is summarized.

Gender-specific risk factors in post-tonsillectomy hemorrhage.

There are gender-specific differences in the frequency and course of different diseases. Specifically, some studies have shown an increased risk of post-tonsillectomy hemorrhage (PTH). The aim of the study was to investigate gender-specific risk factors for hemorrhage after tonsillectomy (TE)/abscess-TE. We anonymously reviewed and recorded the relevant data of all patients (≥14 years) who underwent a TE/abscess-TE between 2011 and 2013 in the ENT Clinic of the Charité Universitätsmedizin Berlin, Campus Benjamin Franklin. A patient survey was used to complete missing data. We analyzed gender-specific risk factors for PTH. During the study period, 460 operations were performed and the data of 250 patients were analyzed (213 TE and 37 abscess-TE). The median patient age was 27 years (ranging from 14 to 83 years). The rate of primary PTH (<24 h after TE/abscess-TE) was 3 %, and the rate of secondary PTH (>24 h) was 23 %. A significantly higher PTH rate was associated with males (p = 0.037), which was still apparent in ages 21-30 after sub-classification. Multivariate analysis calculated diagnosis, regular alcohol consumption and administration of glucocorticoids to be independent risk factors associated with gender. In conclusion, the PTH rate is gender-specific, and male patients are at higher risk, especially in young adulthood. Therefore, doctors should advise male patients of the increased risk of bleeding and stress the importance of compliance. Also, close postoperative follow-up is desirable.

Nodal yield of neck dissections and influence on outcome in laryngectomized patients.

The appropriate extent of neck dissection (ND) in head and neck squamous cell carcinoma (SCC) continues to be investigated. This study aimed to determine whether the extent of ND as measured by nodal yield (NY) is a prognostic factor in patients undergoing primary total laryngectomy (TL) for advanced laryngeal SCC. A retrospective review at a tertiary referral centre identified 54 patients who underwent TL with elective (n = 39, cN0) or therapeutic (n = 15, cN+) ND with curative intent between 2002 and 2014. Survival analysis was obtained via regression analysis, calculated for overall (OS) and disease-free survival (DFS). Stage-independent 5-year OS was 32.1 %. Mean NY was 18.67 (standard deviation 9.898; range 0-45). The rate of cervical lymph node metastasis on pathology (pN+) was 27.8 %. Uni- and multivariate regression analysis detected no association between NY and OS or DFS (P ≥ 0.05). Advantages in OS and DFS were seen among patients without cervical lymph node metastasis (pN0) in comparison to those with pN+ necks (OS: hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.046-0.693; P = 0.013, and DFS: HR 0.190; 95 % CI 0.061-0.590; P = 0.004). ND resulted in pathologic upstaging of the neck in seven patients and downgrading in eight; increasing NY was not associated with an increased probability of a change in nodal stage. No significant association was found between NY and OS or DFS in patients undergoing TL with ND as primary therapy for advanced laryngeal SCC.

Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status.

Data indicate a better prognosis for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). HPV and p16 detection are established markers for HPV-related HNSCC. Both are accepted as survival-independent predictors. Previous studies investigating the survival in HNSCC patients depending on HPV(+/-) and p16(+/-) status consistently found discordant results with p16(-)/HPV(+) and p16(+)/HPV(-). However, no meta-analysis regarding the survival according to combined HPV/p16 status has been performed yet. The objective of this study was to discriminate the impact of combined HPV(+/-) and p16(+/-) status on survival. Data sources were identification and review of publications assessing survival of the distinct subgroups with both p16 and HPV investigated in HNSCC until February, 2015. A meta-analysis was performed to classify survival and clinical outcomes. 18 out of 397 articles (4424 patients) were eligible for the meta-analysis. The percent proportion of the subgroups was 25 % for HPV(+)/p16(+), 61.2 % for HPV(-)/p16(-), 7.1 % for HPV(-)/p16(+) and 6.8 % for HPV(+)/P16(-). The meta-analysis showed a significantly improved 5-year overall survival (OS), 5-year disease-free survival and their corresponding hazard ratio for HPV(+)/p16(+) HNSCC in comparison to HPV(-)/p16(-), HPV(+)/p16(-) and HPV(-)/p16(+). The 5-year OS of the HPV(-)/p16(+) subgroup was intermediate while HPV(+)/p16(-) and HPV(-)/p16(-) HNSCC had the shortest survival. With current therapeutic strategies, survival of patients with HNSCC is better if associated with HPV(+)/p16(+) or HPV(-)/p16(+). Clinical trials are needed to confirm the distinct survival pattern and to investigate possible differences in survival for HPV(+)/p16(-) and HPV(-)/p16(+) HNSCC. To further differentiate p16(+) HNSCC, HPV testing may be advisable.

Subgroup Analysis of Overall Survival among Smoking and Non-Smoking Elderly Patients with HNSCC.

Smoking is a leading cause of head and neck squamous cell carcinoma (HNSCC). However, non-smokers are also affected by HNSCC, and the prognostic factors applicable to older non-smokers with HNSCC are largely unknown. The aim of this study was to determine predictors of overall survival (OS) in patients both with and without a smoking history aged 70 and over at initial diagnosis. Retrospective data of patients aged ≥70 (initial diagnoses 2004-2018) were examined. Evaluated predictors included tumour stage, biological age, health and therapy. A total of 688 patients (520 smokers, 168 non-smokers) were included with a median age of 74. The 5-year OS was 39.6%. Non-smokers had significantly improved OS compared to smokers (52.0% versus 36.0%, p < 0.001). Disease-free survival (DFS) differed significantly between both groups (hazard ratio = 1.3; 95%CI 1.04-1.626). TNM stage and the recommended therapies (curative versus palliative) were comparable. The proportion of p16-positive oropharyngeal carcinomas was significantly higher in non-smokers (76.7% versus 43.8%, p < 0.001). Smokers were significantly more likely to be men (p < 0.001), drinkers (p < 0.001), and have poorer health status (Karnofsky performance status, KPS, p = 0.023). They were also more likely to have additional tumours (p = 0.012) and lower treatment adherence (p = 0.038). Important predictors of OS identified in both groups, were, among others, alcohol abuse, KPS, Charlson comorbidity index, site of primary tumour, UICC stage and treatment received. Elderly non-smokers are also affected by HNSCC, however, both OS and DFS are increased compared to smokers.

Prognostic factors in surgically treated malignant salivary gland tumors.

OBJECTIVES: To identify prognostic factors for evidence-based risk stratification in malignant salivary gland tumors. METHODS: This retrospective study identified 162 patients who presented with malignant salivary gland tumors between 2010 and 2020. Final analysis included 91 patients who underwent surgical treatment at our institution and were followed-up for ≥ 1 year. Medical records were reviewed and patients were categorized according to their risk profile. RESULTS: This study included 91 patients (51 males, 40 females, mean age 61 years). The most frequent entities were adenoid cystic carcinoma (n = 13, 14.3%) and mucoepidermoid carcinoma (n = 12, 13.2%). Kaplan-Meier analysis demonstrated a five-year overall survival (OS) of 66.2% and a recurrence-free survival (RFS) of 50.5%. Age > 60 years (p = 0.011), categorization into high-risk group (p = 0.011), UICC stage (p = 0.020), T stage (p = 0.032), grading (p = 0.045) and vascular invasion (p < 0.001) were significantly associated with OS; age > 60 years (p = 0.014), categorization into high-risk group (p < 0.001), UICC stage (p = 0.021), T stage (p = 0.017), grading (p = 0.011), vascular invasion (p = 0.012) and lymphovascular invasion (p < 0.001) were significantly associated with RFS. Multivariate Cox regression with backward elimination identified T stage (HR 1.835; 95% CI 1.187-2.836; p = 0.006) and grading (HR 2.233; 95% CI 1.113-4.480; p = 0.024) as significant factors for OS. Grading (HR 2.499; 95% CI 1.344-4.648; p = 0.004) was confirmed as a significant factor for RFS. CONCLUSION: Considering the risk of recurrence and distant metastasis in malignant salivary gland tumors, locoregional surgical control may not be sufficient and adjuvant therapies such as radiotherapy and/or systemic therapies should be considered.

Recombinant human beta 2-defensin fusion proteins as a tool to investigate defensin structure and function in small human intestinal tissue samples.

OBJECTIVE: Effects of immune cells on the beta 2 (ß2)-defensin (HBD2) expression and its antibacterial activity in the intestinal mucosa of patients with inflammatory bowel diseases remains unclear. The small size of these proteins presents a major challenge in localizing antibacterial activities in human intestinal tissue. In this study, we evaluated the detection limits at mRNA and protein level by approaching HBD2 from small tissue samples. METHODS: HT-29 colonic epithelial cells were incubated with proinflammatory cytokines before HBD2 mRNA was investigated by quantitative polymerase chain reaction. The HBD2 protein was assessed by Western blot analysis using HBD2 fused with enhanced green fluorescent protein (HBD2-EGFP). Purified HBD2 fused with the glutathione-S-transferase (GST-HBD2) was used to detect antibacterial activity in a densitometric assay. RESULTS: Interleukin (IL)-1ß induced HBD2 mRNA in HT-29 cells; however, tumor necrosis factor-α, IL-6 and IL-17 did not. The Western blot had a sensitivity of 1.5 pmol to detect recombinant HBD2, but did not detect HBD2 in either human intestinal or IL-1ß-treated HT-29 cells. HBD2-EGFP was detected by HBD2-specific Western blot within cell lysates and culture supernants of transfected HT-29 and primary cells. In nanomolar ranges, GST-HBD2 reduced bacterial growth. The HBD2 bioactivity depended on solution conditions, but not on the size of the fusion partner. CONCLUSION: The established fusion proteins provide excellent tools to evaluate expression patterns and antibacterial effects of HBD2 in human intestinal tissue samples.

Modified dindo-clavien system for registration of perioperative complications in children undergoing adenotonsillectomy.

Introduction: Surgical procedures in children are among the most commonly performed procedures in otolaryngology. Perioperative safety and documentation of complications are becoming increasingly important. This study investigates perioperative complications in a clinical cohort of children with adenotonsillar hyperplasia undergoing adenotonsillectomy using the standardized Dindo-Clavien reporting system. Patients and Methods: Retrospective evaluation of 402 children who underwent adenotonsillectomy between 2009 and 2015. Patient parameters including all perioperative complications were investigated. Results: In the study, 124 complications were found (106 mild, 16 severe). According to the Dindo-Clavien classification, 93 grade I, 15 grade II, 5 grade III, 11 grade IV and 0 grade V complications were documented. Complications were associated with additional diagnoses (p = 0.001), long-term medication intake (p = 0.003), duration of hospitalization (p < 0.001) and duration of surgery (p < 0.001), undergoing tonsillotomy (p = 0.022) or tonsillectomy (p < 0.001), differences in ASA score (p = 0.005) and differences in OSA-18 score (p = 0.011). Severe complications, classified as grade III and IV, were associated with premature birth (p = 0.026), additional diagnoses (p = 0.017), long-term medication intake (p < 0.001) and differences in ASA score (p =< 0.001). Conclusion: The Dindo-Clavien classification is a standardized reporting system which can also be used for surgical procedures in children with adenotonsillar hyperplasia. The system shows associations with clinical parameters and thus can help to identify subgroups at risk of severe complications.

Influence of Tumor Site on Survival in Young Patients with Head and Neck Squamous Cell Carcinoma.

The number of patients under the age of 45 diagnosed with head and neck squamous cell carcinomas (HNSCC) is increasing, probably due to the incidence of oropharyngeal cancers. Comparisons of HNSCC in young and old patients regarding tumor site and survival in sample sizes of relevance are rarely published. The aim of the study was to analyze the differences in survival between age groups dependent on tumor site and the influence of oropharyngeal cancers on the rising rates of HNSCC in the young. The records of 4466 patients diagnosed with HNSCC were reviewed retrospectively. Patients younger than 45 years were divided further into four subgroups for specific age differences in the young. The influences of patient and clinicopathological characteristics on survival were assessed using Kaplan-Meier analyses. Among the patient cohort, 4.8% were younger than 45 years. Overall survival (OS) in these patients was better, with a 5-year OS of 66.1% (vs. 46.4%), while relapse-free survival (RFS) was better in the older patient population, with a 5-year RFS of 74.9% (vs. 68.1%). Decreased RFS in the young was found for advanced tumor stages and tumor sited at the larynx. Hypopharynx and advanced stages were independent risk factors for OS under 45 years. Overall, 44.4% of all HNSCC in patients under 30 years were nasopharyngeal cancers, and incidence decreased with age. The incidence of oropharyngeal cancers increased significantly with age. Better OS in the young may be explained by lower tumor and disease stages, whereas oropharyngeal tumors and HPV were not found to cause rising rates of HNSCC. Laryngeal malignancies in young patients might be related to an increased malignant potential and should, consequently, be treated as such.

The Prognostic Significance of p16 and its Role as a Surrogate Marker for Human Papilloma Virus in Oral Squamous Cell Carcinoma: An Analysis of 281 Cases.

BACKGROUND/AIM: This study analyzed the expression of p16 in a large cohort of patients suffering from oral squamous cell carcinoma (OSCC) who received initial surgical therapy in order to evaluate the prognostic significance of p16 expression and to analyze its value as a surrogate marker to determine human papilloma virus (HPV) status. MATERIALS AND METHODS: Immunohistochemical staining of p16 was performed on tissue microarrays. Different expression levels of p16 (>25%; >50%; ≥70%) with a moderate to strong intensity were correlated with the clinical outcome. HPV DNA was analyzed by polymerase chain reaction (PCR). RESULTS: A total of 281 patients were included in this study. The p16 expression obtained using the abovementioned three different cutoffs did not significantly influence 5-year overall survival (OS) (p=0.23; p=0.45; p=0.23) nor recurrence-free survival (RFS) (p=0.79; p=0.45; p=0.142). In univariate Cox regression analysis, the p16 expression level was not a risk factor for OS (HR=0.637; 95%CI=0.271-1.5; p=0.300) and RFS (HR=0.74; 95%CI=0.339-1.61; p=0.449). A total of 17 patients (6.0%) were p16 positive with a cutoff ≥70%. HPV DNA was found in 4/11 of these cases by PCR, resulting in a positive predictive value of 0.36. In patients receiving adjuvant radio(chemo)therapy, a significantly (p=0.042) longer OS was observed in patients with p16 expression greater than 25% vs. ≤25%. CONCLUSION: In comparison with OPSCC, (strong) p16 positivity is rare in OSCC; however, in patients receiving primary surgery with adjuvant radio(chemo)therapy, p16 expression is associated with a higher survival rate. In conjunction with prior studies, p16 does not seem to be a reliable surrogate marker for HPV infection in OSCC.

Predictors for Adherence to Treatment Strategies in Elderly HNSCC Patients.

Finding a cure may be less important than ensuring the quality of life in elderly patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine predictors for adherence. Clinical and pathological data from patients ≥70 years with HNSCC (initial diagnoses 2004-2018) were investigated retrospectively. Evaluated clinical predictors included biological age (Charlson Comorbidity Index; CCI), patient health (Karnofsky Performance Status; KPS) and therapy data. A total of 1125 patients were included. The median age was 75 years, 33.1% reached CCI ≥ 6, and 53.7% reached KPS ≤ 70%. In total, 968 patients were adherent, whereas 157 were nonadherent. Nonadherent patients were significantly more often smokers (p = 0.003), frequent drinkers (p = 0.001), had a worse health status (p ≤ 0.001) and a lower biological age (p = 0.003), an advanced T classification and lymph node involvement or UICC stage (each p ≤ 0.001). Approximately 88.0% of the included patients received a curative treatment recommendation. A total of 6.9% discontinued the therapy, and 7.0% refused the therapy. With the increasing complexity of a recommended therapy, adherence decreased. The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). In contrast to the chronological patient age, biological age is a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.

Duration of deafness impacts auditory performance after cochlear implantation: A meta-analysis.

OBJECTIVE: Hearing loss is a highly disabling condition. Cochlear implantation is an established remedy if conventional hearing aids have failed to alleviate the level of disability. Unfortunately, cochlear implant (CI) performance varies dramatically. This study aims to examine the effects of duration of deafness (DoD) prior to cochlear implantation and the postoperative duration of implant experience with resulting hearing performance in postlingually deaf patients. METHODS: A systematic literature review and two meta-analyses were conducted using the search terms cochlear implant AND duration deafness. Included studies evaluate the correlation between the DoD and auditory performance after cochlear implantation using monosyllabic and sentence tests. Correlation coefficients were determined using Pearson's correlation and Spearman rho. RESULTS: A total of 36 studies were identified and included data on cochlear implantations following postlingual deafness and postoperative speech testing of hearing outcomes for 1802 patients. The mean age ranged from 44 to 68 years with a DoD of 0.1 to 77 years. Cochlear implant use varied from 3 months to 14 years of age. Speech perception, which was assessed by sentence and monosyllabic word perception, was negatively correlated with DoD. Subgroup analyses revealed worse outcomes for longer DoD and shorter postoperative follow-up. CONCLUSION: DoD is one of the most important factors to predict speech perception after cochlear implantation in postlingually deaf patients. The meta-analyses revealed a negative correlation between length of auditory deprivation and postoperative sentence and monosyllabic speech perception. Longer DoD seems to lead to worse CI performance, whereas more experience with CI mitigates the effect.

Impact of Smoking on the Survival of Patients With High-risk HPV-positive HNSCC: A Meta-analysis.

BACKGROUND/AIM: High risk Human papillomavirus (hr-HPV) and smoking are independant risk factors for head and neck squamous cell carcinomas (HNSCC). While hr-HPV+ HNSCC has a better prognosis than smoking-associated HNSCC no systematic data are yet available about the combined risk. PATIENTS AND METHODS: We performed a meta-analysis to assess the overall survival of HNSCC patients relative to the hr-HPV and smoking status. A literature review up to November 2019 was conducted in PubMed and Cochrane Library using the search terms 'HPV, Smoking and HNSCC'. RESULTS: Nine out of 748 articles were included, 1,436 out of 2,080 patients were hr-HPV+ The prevalence of hr-HPV+ smokers was 36%. The meta-analysis showed a significantly better 5-year overall survival for HPV+ non-smokers compared to smokers with risk ratio of 1.94 (95% confidence intervaI=1.46-2.58). CONCLUSION: Smoking is a negative prognostic factor for overall survival in patients with hr-HPV+ HNSCC and should thus be an important part of staging and treatment.

Fever range whole body hyperthermia for re-irradiation of head and neck squamous cell carcinomas: Final results of a prospective study.

OBJECTIVES: Fever-range whole body hyperthermia (FRWBH) has been shown to improve tumor oxygenation in vivo. A prospective pilot study addressed the question if addition of FRWBH to re-irradiation is feasible in recurrent head and neck squamous cell carcinomas (HNSCC) with unfavorable prognostic features. MATERIALS AND METHODS: The study completed accrual with the recruitment of ten patients between April 2018 and March 2020. Re-irradiation was administered using volumetric arc hyperfractionated radiotherapy with bi-daily 1.2 Gray (Gy) single fractions and a total dose of 66 Gy to all macroscopic tumor lesions. Concomitant chemotherapy consisted mostly of cisplatin (7 patients). FRWBH was scheduled weekly during re-irradiation. The study was registered in the clinicaltrials.gov database (NCT03547388). RESULTS: Only five patients received all cycles of FRWBH. Poor patient compliance, active infections during treatment and study restrictions due to the Covid-19 pandemic were the main reasons for omitting FRWBH. No increase of acute toxicity was observed by FRWBH. Exploratory evaluation of outcome data suggests that FRWBH treatment according to protocol does not seem to have a detrimental effect on tumor control or survival and might even increase treatment efficacy. CONCLUSION: FRWBH is difficult to apply concomitant to re-irradiation in HNSCC. No excess toxicity was observed in patients receiving FRWBH and exploratory analyses suggest potential anti-tumor activity and decreased patient-reported depression scores after FRWBH.

Carcinoma of Unknown Primary and the 8th Edition TNM Classification for Head and Neck Cancer.

OBJECTIVE: In the 8th Edition TNM Classification for Head and Neck Cancer, the classification for carcinoma of unknown primary (CUP) changed in addition to oropharyngeal carcinomas. The current classification considers extranodal extension (ENE), determination of p16 (surrogate marker for human papillomavirus), and detection of Epstein-Barr virus (EBV). The aim of this study was to investigate the influence of the new classification on the prognosis of p16-positive and p16-negative CUP and the impact of EBV proof. METHODS: Clinical and pathological data from patients with CUP of the head and neck between 2009 and 2018 were evaluated. The 7th (UICC7) and 8th (UICC8) edition of the Union for International Cancer Control staging system were applied and compared. RESULTS: There were 97 patients treated, 26.8% women and 73.2% men. The average age at initial diagnosis was 64.6 years. Of which, 58.8% had a documented history of smoking, 37.1% were positive for p16, 4.1% were positive for EBV, and 66% had ENE. Most of the patients were at stage III/IVa (78.4% according to UICC7). According to UICC8, p16+ patients were mainly at stage I (86.1%), and p16- at stage IVb (56.1%). P16 status (P = .002), ENE (P = .001), nodal category (TNM7, P < .001), UICC stage (TNM7, P < .001) and UICC stage (TNM8, P < .001) had a significant impact on survival in the univariate analysis. The 8th TNM classification resulted in a downstaging of p16-positive CUP syndromes and an upstaging of p16-negative syndromes. CONCLUSION: The 8th TNM classification shows the lower UICC stage in p16-positive CUP syndromes. The prognostic significance for survival has improved from the 7th to the 8th TNM classification. LEVEL OF EVIDENCE USING THE 2011 OCEBM: Level 3. Laryngoscope, 131:E2534-E2542, 2021.