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BACKGROUND/AIM: Transforming growth factor-ß (TGF-ß) plays a significant role in the formation of different cancer subtypes. There is evidence that TGF-ß pathways promote cancerogenic cell characteristics but also have tumor-suppressor capabilities. The tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib, gefitinib, and everolimus are approved as targeted therapies for several tumor entities, including head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the effects of these substances on the expression levels of TGFß1 and TGF-ß receptor type 2 (TGFßR2) in HPV-negative and HPV-positive SCC cell cultures. MATERIALS AND METHODS: Expression patterns of TGFß1 and TGFßR2 were determined using enzyme-linked immunosorbent assay (ELISA) in three HNSCC cell lines (i.e., HNSCC-11A, HNSCC-14C, and CERV196). These cells were incubated with nilotinib, dasatinib, erlotinib, gefitinib, and everolimus (20 µmol/l) and compared to a chemonaive control. An assessment of concentration levels was conducted after 24, 48, 72, and 96 h of treatment. RESULTS: Statistically significant changes in the expression levels of TGFß1 and TGFßR2 were found in all tested cell cultures (p<0.05) compared to the negative control. An increase in TGFß-R2 expression was detected after treatment with most of the tested tyrosine kinase inhibitors, whereas a reduction in TGFß1 was observed. The addition of everolimus had the opposite effect on both TGFßR2 and TGF-B1- expression. CONCLUSION: Expression of TGFß1 and TGFßR2 was detected in all cultured HNSCC cell lines. Nilotinib, dasatinib, erlotinib, gefitinib, and everolimus had an impact on the expression levels of TGFß1 and TGFßR2 in vitro.
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Dasatinibe , Everolimo , Inibidores de Proteínas Quinases , Receptor do Fator de Crescimento Transformador beta Tipo II , Fator de Crescimento Transformador beta1 , Humanos , Everolimo/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Dasatinibe/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Gefitinibe/farmacologia , Cloridrato de Erlotinib/farmacologia , Pirimidinas/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Working during pregnancy and breastfeeding is a special situation for both the employee and the employer/supervisor. The amended version of the Maternity Protection Act (MuSchG), which came into force on January 1st, 2018, protects the health of women and their children while working, training or studying during pregnancy, after giving birth and while breastfeeding. Women should be able to continue their employment or related activities during this time without jeopardising their health or that of their child. This law was furthermore reformed to prevent discrimination against the working mother during this time. In order to create the best and safest possible framework conditions for employment during pregnancy and breastfeeding, the DGHNO-KHC and the BVHNO would like to present a "general positive list" and a "positive list for surgical activities" as part of this statement, which should serve as a guideline for all relevant parties. This agreed positive list is intended to enable pregnant and breastfeeding doctors to carry out patient-related activities as well as head and neck surgeries in accordance with the MuSchG of 2018. Hereby, affected colleagues should have the opportunity to continue working self-determined.
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Introduction The kinetic of C-reactive protein (CRP) in the early phase of therapy with checkpoint inhibitors (CPI) and its prognostic value has already been investigated in several tumor entities. In particular, flare dynamics have been described as a positive prognostic parameter. The aim of this retrospective study is to examine the extent to which such an application can also be transferred to patients with recurrent or metastatic squamous cell carcinoma of the head and neck region (R/M-HNSCC). Material and Methods All patients treated with CPI for R/M-HNSCC at our clinic between 2018 and 2023 were included (n = 44). Demographic, clinical, histopathologic and laboratory data were extracted from the digital patient records and statistically analyzed. We then examined the CRP kinetic using two previously published classifications and proposed a new classification ourselves. Subsequently, correlation analyses were performed with the overall survival (OS) of the patients. Results Of the two CRP kinetic classifications previously published, only one showed a correlation with the result of the first re-staging, and neither showed a correlation with the OS of R/M-HNSCC patients. Our new CRP kinetic classification showed a significant association with OS in R/M-HNSCC patients (p = 0.05). In a multivariate analysis, our CRP kinetic classification (p = 0.007) and the outcome of the first re-staging (p = 0.002) were significant independent factors for OS. Discussion Our novel CRP kinetic classification significantly correlates with OS in R/M-HNSCC patients, indicating a potential prognostic marker. Existing classifications from other cancer entities showed limited prognostic significance, emphasizing the need for tailored markers. For validation, however, testing on larger R/M-HNSCC patient collectives is necessary.
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In CUP syndrome (CUP = cancer of unknown primary) there are 1 or more metastases of a primary tumor that cannot be localized despite extensive diagnostics. CUP syndrome accounts for 5% of all human malignancies, making it one of the 10 most common forms of cancer. In addition to inflammatory lymph node enlargement and benign changes such as cervical cysts, lymph node metastases are among the most common cervical masses. Cervical CUP syndrome is a histologically confirmed cervical lymph node metastasis with an unknown primary tumor. In addition to anamnesis, clinical examination and histological confirmation, diagnostics include radiological imaging using PET-CT and panendoscopy with histological primary tumor search. Treatment options include surgical therapy with neck dissection and chemoradiotherapy.
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Metástase Linfática , Neoplasias Primárias Desconhecidas , Humanos , Neoplasias Primárias Desconhecidas/terapia , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/patologia , Metástase Linfática/patologia , Esvaziamento Cervical , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Síndrome , Terapia Combinada , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Diagnóstico Diferencial , QuimiorradioterapiaRESUMO
Salivary duct carcinomas (SDC) of the parotid gland are rarely occurring highly malignant tumors. A 65-year-old man presented with a preauricular mass. After surgical treatment and histologic examination, the findings were interpreted as a squamous cell carcinoma (SCC) metastasis of the parotid gland deriving from a cancer of unknown primary DD primary SCC of the parotid gland. Adjuvant platinum-based radiochemotherapy was administered in domo. However, re-staging revealed multiple size-progressive pulmonary round lesions. After resection and histological examination of a pulmonary mass and in synopsis with the primary tumor, the initial diagnosis of SCC was revised to SDC of the parotid gland. With positive HER-2 status, off-label trastuzumab/docetaxel was initiated in an individual healing attempt, during which the pulmonary metastases showed clear progression. Consequently, the patient received immunotherapy with nivolumab according to his negative PD-L1 status. After 57 cycles of nivolumab, the patient presents with partial remission and in good condition. We report, for the first time, a robust response of metastatic SDC to checkpoint inhibition with nivolumab without additional radiotherapy.
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Nivolumabe , Humanos , Masculino , Idoso , Nivolumabe/uso terapêutico , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/terapia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Ductos Salivares/patologia , Resultado do Tratamento , Carcinoma Ductal/terapia , Carcinoma Ductal/tratamento farmacológico , Carcinoma Ductal/diagnóstico , Metástase Neoplásica , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapiaRESUMO
Study background: Newborn infection and sepsis remain serious problems. Guideline-compliant therapy includes, among other therapeutics, calculated intravenous antibiosis with gentamicin. One of the known side effects of gentamicin is severe vestibulotoxicity, which can be detected using the video head impulse test (VHIT), which is a sensitive examination method for the detection of vestibular hypofunction in children and adults. Previous studies on the vestibulotoxicity of gentamicin in newborns were carried out using caloric testing, rotary testing, and electronystagmography. Nevertheless, there are currently no data available on VHIT examinations in children who have been treated with neonatal gentamicin therapy. Methods: A single-center, prospective cross-sectional study, was conducted at a tertial referral center. VHIT was performed on 23 children aged 3-7 years who had received intravenous gentamicin therapy for at least five days as part of the treatment of newborn sepsis between 2012 and 2016. Main outcome was median gain and occurrence of refixational saccades as measured with VHIT. In addition, the children's parents received questionnaires to detect possible risk factors and vestibular and cochlear abnormalities. Results: Out of 23 children with a mean age of four years and seven months (ranging from 3 to 7 years), 11 (47.8%) indicated abnormal results in VHIT. The VHIT results were unilaterally abnormal in six children (26.1%) and bilaterally abnormal in five others (21.7%). Additionally, five of the children with an abnormal HIT had abnormalities, as found in the questionnaire results. Conclusion: and Relevance: Almost half of the children observed after having undergone gentamicin therapy as newborns showed abnormalities in VHIT, although they did not show any clinical signs of disbalance or vestibular hypofunction. VHIT can serve as a sensitive investigation method for the early screening of post-therapeutic vestibulotoxic side effects after gentamicin therapy in children. Additionally, VHIT can enable early intervention in these children.
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Introduction: A 2½ D point cloud registration method was developed to generate digital twins of different tissue shapes and resection cavities by applying a machine learning (ML) approach. This demonstrates the feasibility of quantifying soft tissue shifts. Methods: An ML model was trained using simulated surface scan data obtained from tumor resections in a pig head cadaver model. It hereby uses 438 2½ D scans of the tissue surface. Tissue shift was induced by a temperature change from 7.91 ± 4.1°C to 36.37 ± 1.28°C. Results: Digital twins were generated from various branched and compact resection cavities (RCs) and cut tissues (CT). A temperature increase induced a tissue shift with a significant volume increase of 6 mL and 2 mL in branched and compact RCs, respectively (p = 0.0443; 0.0157). The volumes of branched and compact CT were decreased by 3 and 4 mL (p < 0.001). In the warm state, RC and CT no longer fit together because of the significant tissue deformation. Although not significant, the compact RC showed a greater tissue deformation of 1 µL than the branched RC with 0.5 µL induced by the temperature change (p = 0.7874). The branched and compact CT forms responded almost equally to changes in temperature (p = 0.1461). Conclusions: The simulation experiment of induced soft tissue deformation using digital twins based on 2½ D point cloud models proved that our method helps to quantify shape-dependent tissue shifts.
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Introduction: Checkpoint inhibitors, such as PD1 inhibitors, represent an important pillar in the therapy of advanced malignancies of the head and neck region. The most relevant complications are immune-related adverse effects (irAEs), which represent an immense burden for patients. Currently, no sufficient stratification measures are available to identify patients at increased risk of irAEs. The aim of this retrospective study was to examine whether demographic, histopathological, clinical, or laboratory values at the start of CPI therapy represent a risk factor for the later occurrence of autoimmune complications. Material and methods: Data from 35 patients between 2018 and 2021 who received therapy with nivolumab or pembrolizumab for head and neck malignancy were analyzed and assessed for any associations with the subsequent occurrence of irAEs. Results: IrAE developed in 37% of patients, with pneumonitis being the most common form (14%). Pneumonitis was found in patients with an average significantly lower T-stage of primary tumors. An increase in basophilic leukocytes was found in patients with dermatitis later in the course. When thyroiditis developed later, the patients had a higher CPS score and lower monocyte levels. Discussion: Even though individual laboratory values at the beginning of therapy might show a statistical association with the later occurrence of irAEs, neither demographic, histopathological, nor laboratory chemistry values seem to be able to generate a sound and reliable risk profile for this type of complication. Therefore, patients need to be educated and sensitized to irAEs, and regular screening for irAEs should be carried out.
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Small extracellular vesicles from saliva (SEVs) have high potential as biomarkers in Head and Neck cancer (HNC). However, there is no common consensus on the ideal method for their isolation. This study compared different ultracentrifugation (UC) methods (durations and + /- additional purification) with size exclusion chromatography (SEC) and investigated the potential of SEVs as diagnostic biomarkers and their biological activity on NK and CD8+ T cells. SEVs from 19 HNC patients and 8 healthy donors (HDs) were thoroughly characterized. Transmission electron microscopy confirmed the isolation of vesicles by all methods. The average size determined via nanoparticle-tracking analysis was smaller for SEVs isolated by SEC than UC. The highest particle-to-protein yield was achieved by UC (3 h + 3 h) (UCopt) and SEC. However, SEC yielded considerably fewer SEVs. Comparing the surface marker cargo, SEVs isolated by UCopt from HNC patients carried more PD-L1, FasL, and TGF-ß than SEVs from HDs. These levels correlated with tumor stage and HPV status. SEVs downregulated NKG2D expression on primary NK cells. HNC SEVs accelerated CD8+ T cell death compared to HD SEVs. This study suggests that UCopt is preferable when isolation of a high particle-to-protein load is required. Especially PD-L1 and FasL on SEVs hold substantial potential as diagnostic biomarkers.
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Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Humanos , Saliva , Antígeno B7-H1 , Linfócitos T CD8-Positivos , BiomarcadoresRESUMO
Tissue engineering (TE) techniques offer solutions for tissue regeneration but require large quantities of cells. For microtia patients, TE methods represent a unique opportunity for therapies with low donor-site morbidity and reliance on the surgeon's individual expertise. Microtia-derived chondrocytes and perichondrocytes are considered a valuable cell source for autologous reconstruction of the pinna. The aim of this study was to investigate the suitability of perichondrocytes from microtia patients for autologous reconstruction in comparison to healthy perichondrocytes and microtia chondrocytes. Perichondrocytes were isolated via two different methods: explant culture and enzymatic digestion. The isolated cells were analyzed in vitro for their chondrogenic cell properties. We examined migration activity, colony-forming ability, expression of mesenchymal stem cell markers, and gene expression profile. We found that microtic perichondrocytes exhibit similar chondrogenic properties compared to chondrocytes in vitro. We investigated the behavior in three-dimensional cell cultures (spheroids and scaffold-based 3D cell cultures) and assessed the expression of cartilage-specific proteins via immunohistochemistry, e.g., collagen II, which was detected in all samples. Our results show that perichondrocytes from microtia patients are comparable to healthy perichondrocytes and chondrocytes in terms of chondrogenic cell properties and could therefore be a promising cell source for auricular reconstruction.
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Microtia Congênita , Células-Tronco Mesenquimais , Humanos , Condrócitos , Condrogênese , Nível de SaúdeRESUMO
BACKGROUND: Ultrasound is an important imaging method in the head and neck area. It is readily available, dynamic, inexpensive, and does not involve radiation exposure. Interventions in the complex head and neck anatomy require good orientation, which is supported by navigation systems. OBJECTIVE: This work aimed to develop a new ultrasound-controlled navigation system for taking biopsies of small target structures in the head and neck region. METHODS: A neck phantom with sonographically detectable masses (size: 8-10â¯mm) was constructed. These were automatically segmented using a ResNet-50-based deep neural network. The ultrasound scanner was equipped with an individually manufactured tracking tool. RESULTS: The positions of the ultrasound device, the masses, and a puncture needle were recorded in the world coordinate system. In 8 out of 10 cases, an 8mm mass was hit. In a special evaluation phantom, the average deviation was calculated to be 2.5â¯mm. The tracked biopsy needle is aligned and navigated to the masses by auditory feedback. CONCLUSION: Outstanding advantages compared to conventional navigation systems include renunciation of preoperative tomographic imaging, automatic three-dimensional real-time registration that considers intraoperative tissue displacements, maintenance of the surgeon's optical axis at the surgical site without having to look at a navigation monitor, and working freely with both hands without holding the ultrasound scanner during biopsy taking. The described functional model can also be used in open head and neck surgery.
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Cirurgia Assistida por Computador , Cirurgia Assistida por Computador/métodos , Ultrassonografia , Pescoço/diagnóstico por imagem , Cabeça/diagnóstico por imagem , BiópsiaRESUMO
Hypoglossal stimulation is a safe and effective treatment option for patients with obstructive sleep apnea and unsuccessful PAP therapy. A number of criteria must be met for the indication: proof of failed PAP therapy and ineffectiveness of the other therapy alternatives, AHI of 15-65/h (a relevant number of central and/or mixed apneas should be excluded) and BMI up to max. 35kg/m2. In the case of the respiratory-synchronous and bilateral stimulation system, a complete concentric collapse at the velum level should currently be ruled out in DISE. In the future, stimulation of the branch of the ansa cervicalis innervating the sternothyroid muscle and the ramus internus of the superior laryngeal nerve could open up additional treatment options.
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Terapia por Estimulação Elétrica , Apneia Obstrutiva do Sono , Humanos , Polissonografia , Apneia Obstrutiva do Sono/cirurgia , Resultado do Tratamento , Terapia por Estimulação Elétrica/métodos , Nervo Hipoglosso/cirurgiaRESUMO
Microtia is a congenital condition of abnormal development of the outer ear. Tissue engineering of the ear is an alternative treatment option for microtia patients. However, for this approach, the identification of high regenerative cartilage progenitor cells is of vital importance. Raman analysis provides a novel, non-invasive, label-free diagnostic tool to detect distinctive biochemical features of single cells or tissues. Using micro-Raman spectroscopy, we were able to distinguish and characterize the particular molecular fingerprints of differentiated chondrocytes and perichondrocytes and their respective progenitors isolated from healthy individuals and microtia patients. We found that microtia chondrocytes exhibited lower lipid concentrations in comparison to healthy cells, thus indicating the importance of fat storage. Moreover, we suggest that collagen is a useful biomarker for distinguishing between populations obtained from the cartilage and perichondrium because of the higher spectral contributions of collagen in the chondrocytes compared to perichondrocytes from healthy individuals and microtia patients. Our results represent a contribution to the identification of cell markers that may allow the selection of specific cell populations for cartilage tissue engineering. Moreover, the observed differences between microtia and healthy cells are essential for gaining better knowledge of the cause of microtia. It can be useful for designing novel treatment options based on further investigations of the discovered biochemical substrate alterations.
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Neurootologic disorders of the inner ear associated with symptoms such as tinnitus, vertigo, and hearing loss are common and often cause significant distress to affected patients. Treatment options are usually limited. There are now some indications for which intratympanic drug application is a possible treatment option. Intratympanic drug administration is a simple, inexpensive therapy option with few side effects that can be used on an outpatient basis. Therefore, it should not be disregarded when indicated.
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Surdez , Orelha Interna , Zumbido , Humanos , Preparações Farmacêuticas , Zumbido/tratamento farmacológico , VertigemRESUMO
Digital twins derived from 3D scanning data were developed to measure soft tissue deformation in head and neck surgery by an artificial intelligence approach. This framework was applied suggesting feasibility of soft tissue shift detection as a hitherto unsolved problem. In a pig head cadaver model 104 soft tissue resection had been performed. The surface of the removed soft tissue (RTP) and the corresponding resection cavity (RC) was scanned (N = 416) to train an artificial intelligence (AI) with two different 3D object detectors (HoloLens 2; ArtecEva). An artificial tissue shift (TS) was created by changing the tissue temperature from 7,91±4,1°C to 36,37±1,28°C. Digital twins of RTP and RC in cold and warm conditions had been generated and volumes were calculated based on 3D surface meshes. Significant differences in number of vertices created by the different 3D scanners (HoloLens2 51313 vs. ArtecEva 21694, p<0.0001) hence result in differences in volume measurement of the RTC (p = 0.0015). A significant TS could be induced by changing the temperature of the tissue of RC (p = 0.0027) and RTP (p = <0.0001). RC showed more correlation in TS by heating than RTP with a volume increase of 3.1 µl or 9.09% (p = 0.449). Cadaver models are suitable for training a machine learning model for deformable registration through creation of a digital twin. Despite different point cloud densities, HoloLens and ArtecEva provide only slightly different estimates of volume. This means that both devices can be used for the task.TS can be simulated and measured by temperature change, in which RC and RTP react differently. This corresponds to the clinical behaviour of tumour and resection cavity during surgeries, which could be used for frozen section management and a range of other clinical applications.
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Inteligência Artificial , Cabeça , Animais , Suínos , Cabeça/cirurgia , CadáverRESUMO
Although checkpoint inhibitors (CPI) have recently extended the treatment options and improved clinical response of advanced stage head and neck squamous cell carcinoma (HNSCC), treatment success remains unpredictable. Programmed cell death ligand1 (PDL1) is a key player in immunotherapy. Tumor cells, and exosomes derived therefrom, are carriers of PDL1 and efficiently suppress immune responses. The aim of the present study was to analyze the influence of established therapies on PDL1 expression of HNSCC cell lines and their exosomes. The HNSCC cell lines, UMSCC11B, UMSCC14C and UMSCC22C were treated with fractionated radiotherapy (RT; 5x2 Gy), cisplatin (CT) and cetuximab (Cetux) as monotherapy, or combined therapy, chemoradiotherapy (CRT; RT and CT) or radioimmunotherapy (RT and Cetux). The expression of PDL1 and phosphorylated (p)ERK1/2 as a mediator of radioresistance were assessed using western blotting, immunohistochemistry and an ex vivo vital tissue culture model. Additionally, exosomes were isolated from concentrated supernatants of the (un)treated HNSCC cell lines by size exclusion chromatography. Exosomal protein expression levels of PDL1 were detected using western blotting and semiquantitative levels were calculated. The functional impact of exosomes from the (un)treated HNSCC cell lines on the proliferation (MTS assay) and apoptosis (Caspase 3/7 assay) of the untreated HNSCC cell lines were measured and compared. The HNSCC cell lines UMSCC11B and UMSCC22B showed strong expression of pERK1/2 and PDL1, respectively. RT upregulated the PDL1 expression in UMSCC11B and UMSCC14C and in exosomes from all three cell lines. CT alone induced PDL1 expression in all cell lines. CRT induced the expression of PDL1 in all HNSCC cell lines and exosomes from UMSCC14C and UMSCC22B. The data indicated a potential coregulation of PDL1 and activated ERK1/2, most evident in UMSCC14C. Exosomes from irradiated UMSCC14C cells protected the unirradiated cells from apoptosis by Caspase 3/7 downregulation. The present study suggested a tumor cellmediated regulation of PDL1 upon platinumbased CRT in HNSCC and in exosomes. A coregulation of PDL1 and MAPK signaling response was hypothesized.
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Exossomos , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Caspase 3/metabolismo , Exossomos/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Cetuximab/farmacologia , Cisplatino/farmacologia , Linhagem Celular TumoralRESUMO
The 2018 template for otorhinolaryngology specialist training of the German Medical Association is increasingly implemented by the federal associations. In this regard, the German Society recommended an otorhinolaryngology resident training plan for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) together with the Professional Association of German Otorhinolaryngologists as a suggested guideline for the federal medical associations. In this context, the state medical associations currently work on criteria on the basis of which otorhinolaryngologists and their training institutions can be granted authority for such a certified otorhinolaryngology resident training program.The DGHNO-KHC last made recommendations for the granting of authorizations for specialist training in otorhinolaryngology in 1999. Many contents have changed as a result of the 2018 model specialist training regulations. Therefore, a scientifically formulated proposal for the granting of continuing education authorizations is herewith provided as recommendation to the federal state medical associations.
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Otolaringologia , Humanos , Otolaringologia/educação , Especialização , AlemanhaRESUMO
BACKGROUND: In Head and neck cancer (HNC) angiogenesis is essential for tumor progression and metastasis. Small extracellular vesicles (sEVs) from HNC cell lines alter endothelial cell (EC) functions towards a pro-angiogenic phenotype. However, the role of plasma sEVs retrieved from HNC patients in this process is not clear so far. METHODS: Plasma sEVs were isolated on size exclusion chromatography columns from 32 HNC patients (early-stage UICC I/II: 8, advanced-stage UICC III/IV: 24), 12 patients with no evident disease after therapy (NED) and 16 healthy donors (HD). Briefly, sEVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), BCA protein assays and Western blots. Levels of angiogenesis-associated proteins were determined using antibody arrays. The interaction of fluorescently-labeled sEVs with human umbilical vein ECs was visualized by confocal microscopy. The functional effect of sEVs on tubulogenesis, migration, proliferation and apoptosis of ECs was assessed. RESULTS: The internalization of sEVs by ECs was visualized using confocal microscopy. Based on antibody arrays, all plasma sEVs were enriched in anti-angiogenic proteins. HNC sEVs contained more pro-angiogenic MMP-9 and anti-angiogenic proteins (Serpin F1) than HD sEVs. Interestingly, a strong inhibition of EC function was observed for sEVs from early-stage HNC, NED and HD. In contrast, sEVs from advanced-stage HNC showed a significantly increased tubulogenesis, migration and proliferation and induced less apoptosis in ECs than sEVs from HD. CONCLUSIONS: In general, plasma sEVs carry a predominantly anti-angiogenic protein cargo and suppress the angiogenic properties of ECs, while sEVs from (advanced-stage) HNC patients induce angiogenesis compared to HD sEVs. Thus, tumor-derived sEVs within the plasma of HNC patients might shift the angiogenic switch towards angiogenesis.