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.

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.

[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.

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.

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.

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.

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.

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.

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.

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.

Prognostic Factors Predict Oncological Outcome in Older Patients With Head and Neck Cancer Undergoing Chemoradiation Treatment.

PURPOSE: Older patients with head and neck cancer (HNC) represent a challenging group, as frailty and comorbidities need to be considered. This study aimed to evaluate the efficacy and side effects of curative and palliative (chemo) radiation ([C]RT) with regard to basic geriatric screening in older patients. METHODS: This study included HNC patients aged ≥70 years who were treated with curative or palliative (C)RT. Clinicopathological data including Charlson Comorbidity Index (CCI), Karnofsky performance status (KPS), and treatment data were analyzed as predictors of overall survival (OS). RESULTS: A total of 271 patients (median age, 74 years) were enrolled. The majority had UICC stage III/IV (90%) and underwent curative treatment (85.2%). A total of 144 (53.1%) patients received definitive and 87 (32.1%) had adjuvant (C)RT. Overall, 40 patients (14.8%) received palliative (C)RT. Median follow-up duration (curative setting) was 87 months, and the 2- and 5-year OS rates were 57.8 and 35.9%, respectively. Median OS was significantly different for age ≤75 vs. >75 years, CCI <6 vs. ≥6, KPS ≥70 vs. <70%, Tx/T1/T2 vs. T3/T4, and adjuvant vs. definitive (C)RT, respectively. Age 70-75 years (p = 0.004), fewer comorbidities when CCI < 6 (p = 0.014), good KPS ≥ 70% (p = 0.001), and adjuvant (C)RT (p = 0.008) independently predicted longer survival. Palliative RT resulted in a median OS of 4 months. CONCLUSION: Older age, lower KPS, higher CCI, and definitive (C)RT are indicators of worse survival in older patients with HNC treated curatively. Without a comprehensive geriatric assessment in patients aged >75 years, the KPS and CCI can be useful tools to account for "fitness, vulnerability or frailty" to help in treatment decision-making.

Cystic Lateral Neck Lesions: Etiologic and Differential Diagnostic Significance in a Series of 133 Patients.

BACKGROUND: Patients presenting with a cystic lateral neck lesion may present diagnostic challenges against a backdrop of varied non-malignant and malignant etiologies. PATIENTS: A total of 133 consecutive cases who underwent cystic neck tumor removal were evaluated for etiology and diagnostic procedure in order to develop an algorithm for therapeutic efficiency. RESULTS: In 92 of 133 cases, a non-malignant tumor was diagnosed. In 41 cases, malignant lymphadenopathy was found. In cases with malignancy, males (p=0.001) and the elderly (p=0.001) were affected more frequently. Primary tumors were discovered by pan-endoscopy before neck surgery or in a second pan-endoscopy (with tonsillectomy and mapping biopsies) in cases with histologically confirmed squamous cell carcinoma. During intraoperative frozen-section evaluation (40 cases), a total of 30 patients underwent neck dissection during the first neck operation. CONCLUSION: In patients older than 40 years who present with cystic neck lesions, we recommend pan-endoscopy and intraoperative frozen section in cases where malignancy is suspected in order to avoid secondary neck dissections and delays in therapy.

[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.

Metastases to Both Parotid Glands Six and Twelve Years after Resection of Renal Cell Carcinoma.

Metastases of renal cell carcinoma (RCC) involving the parotid gland are very rare. We present to our knowledge the first case of a 74-year-old woman with metastases of an RCC which affected both parotid glands six and twelve years following curative therapy.

Meta-analysis of subjective complaints of vertigo and vestibular tests after cochlear implantation.

OBJECTIVE: Postoperative vertigo is a common complaint after cochlear implantation, but published incidence rates differ vastly. The aim of the present study was to investigate both subjective complaints of vertigo before and after cochlear implantation and related vestibular diagnostic tests on cochlear implant candidates. DATA SOURCES: We performed a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement in PubMed, Cochrane Register, and EMBASE. REVIEW METHODS: We presented 116 eligible studies investigating subjective complaints of vertigo after cochlear implantation and/or related vestibular diagnostic tests. We conducted three meta-analyses of 46 eligible studies with matched pre- and postoperative data to calculate the odds ratio of new vertigo onset, as well as the impairment of vestibular receptors measured by nystagmography and cervical vestibular evoked myogenic potentials (cVEMP). Postoperative vertigo was calculated from 95 studies and further subdivided by mean age with pooled data. RESULTS: We observed a significant increase in postoperative vertigo and significant impairment of nystagmography and cVEMP detection. Vertigo after cochlear implantation was reported in 9.3% of the patients with a continuous increase in patient age at surgery. In a subgroup of studies, new onset of vertigo was found in 17.4% of the patients. In addition, 7.2% of the patients had persisting vertigo complaints, whereas 11.6% described an altered vertigo quality and 7.7% had their preoperative complaints resolved. A comparison of round window approach and cochleostomy revealed significantly increased vertigo after cochleostomy. Both insertion methods showed similar effects in nystagmography and cVEMP testing. CONCLUSION: Cochlear implantation has a significant impact on subjective vertigo and vestibular receptor function. This is affected by the patient's age at the time of surgery. The surgical technique (round window or cochleostomy) may influence the outcome, but this requires further investigation. Younger patients may compensate better following vestibular dysfunction. Perioperative testing is required to correlate vestibular impairment and subjective complaints. Laryngoscope, 2018 Laryngoscope, 128:2110-2123, 2018.

Etiologic and differential diagnostic significance of tumor location in the supraclavicular fossa.

OBJECTIVE: Patients presenting with a cervical mass are common for head and neck specialists and present a diagnostic challenge against the backdrop of a wide variety of etiologies. The objective of the present study was to evaluate the significance of a mass in the supraclavicular fossa for etiology, diagnostic procedure, and therapy. STUDY DESIGN: Individual retrospective cohort study. METHODS: We reviewed the data of 211 consecutive cases (116 male, 95 female) with excisional biopsy or tumor removal of a supraclavicular mass. RESULTS: In 202 of 211 cases, a biopsy was taken from a lymph node. In 182 biopsies, a malignant lymphadenopathy was found (117 metastases, 65 malignant lymphoma). The histologic findings of metastatic diseases were adenocarcinoma (48), followed by squamous cell carcinoma (22). The majority of primary carcinomas were located below the clavicle (94), in the lung (32), in the breast (29), and in the head and neck region (18). In the left supraclavicular fossa, only metastases of the genitourinary tract were significantly more frequent (16 of 17). In nonmalignant tumors (29), tuberculosis (11) was most prevalent. In 79% of biopsies, the neck mass was the first manifestation of the disease. CONCLUSION: The location of a cervical mass in the supraclavicular fossa provides a strong indication of malignancy. A biopsy is mandatory in the majority of patients presenting with a supraclavicular mass. In cases of metastatic disease, the location of a cervical mass helps identify the primary site. Histologic findings are essential for further diagnostic steps, therapy, and prognosis. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:646-650, 2018.

Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype.

Consistent discrepancies in the p16/HPV-positivity have been observed in head and neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+ and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. We performed a meta-analysis to classify clinical outcomes of the distinct subgroups with combined p16 and HPV detection. 25 out of 1677 publications fulfilled the inclusion criteria. The proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV-/p16-, 6.7% for HPV-/p16+ and 7.3% for HPV+/P16-. The HPV+/p16+ subgroup had a significantly improved 5-year overall-survival (OS) and disease-free-survival in comparison to others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV-/p16+ HNSCC was intermediate while HPV+/p16- and HPV-/p16- had the shortest survival outcomes. The clearly distinct survival of HPV-/p16+ cancers may characterize a new relevant HPV-independent subtype yet to be biologically characterized. The possibility also exists that in some HPV+/p16+ cancers HPV is an innocent bystander and p16 is independently positive. Therefore, in perspective, HPV-testing should distinguish between bystander HPV and truly HPV-driven cancers to avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.