Tissue contexture determines the pattern and density of tumor-infiltrating immune cells in HPV-associated squamous cell carcinomas of oropharynx and uterine cervix.

The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, the influence of the tissue contexture on the composition of the tumor microenvironments of virally induced tumors is not clearly understood. Therefore, we analyzed the immune landscape of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and squamous cell carcinoma of uterine cervix (CESC). We employed multiplex immunohistochemistry and immunofluorescence to evaluate the density and spatial distribution of immune cells in retrospective cohorts of OPSCC and CESC patients. This approach was complemented by transcriptomic analysis of purified primary tumor cells and in silico analysis of publicly available RNA sequencing data. Transcriptomic analysis showed similar immune profiles in OPSCC and CESC samples. Interestingly, immunostaining of OPSCC tissues revealed high densities of immune cells in both tumor stroma and tumor epithelium, whereas CESC samples were mainly characterized by the lack of immune cells in the tumor epithelium. However, in contrast to other immune cell populations, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were abundant in both segments of CESC samples and CESC-derived tumor cells expressed markedly higher levels of the PMN-MDSC chemoattractants CXCL1, CXCL5, and CXCL6 than OPSCC tumor cells. Taken together, despite their having the same etiologic agent, the immune infiltration pattern significantly differs between OPSCC and CESC, with a noticeable shift toward prominent MDSC infiltration in the latter. Our data thus present a rationale for a diverse approach to targeted therapy in patients with HPV-associated tumors of different tissue origins.

Consensus for voice quality assessment in clinical practice: guidelines of the European Laryngological Society and Union of the European Phoniatricians.

INTRODUCTION: To update the European guidelines for the assessment of voice quality (VQ) in clinical practice. METHODS: Nineteen laryngologists-phoniatricians of the European Laryngological Society (ELS) and the Union of the European Phoniatricians (UEP) participated to a modified Delphi process to propose statements about subjective and objective VQ assessments. Two anonymized voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 3/4. The statements with ≥ 3/4 score by 60-80% of experts were improved and resubmitted to voting until they were validated or rejected. RESULTS: Of the 90 initial statements, 51 were validated after two voting rounds. A multidimensional set of minimal VQ evaluations was proposed and included: baseline VQ anamnesis (e.g., allergy, medical and surgical history, medication, addiction, singing practice, job, and posture), videolaryngostroboscopy (mucosal wave symmetry, amplitude, morphology, and movements), patient-reported VQ assessment (30- or 10-voice handicap index), perception (Grade, Roughness, Breathiness, Asthenia, and Strain), aerodynamics (maximum phonation time), acoustics (Mean F0, Jitter, Shimmer, and noise-to-harmonic ratio), and clinical instruments associated with voice comorbidities (reflux symptom score, reflux sign assessment, eating-assessment tool-10, and dysphagia handicap index). For perception, aerodynamics and acoustics, experts provided guidelines for the methods of measurement. Some additional VQ evaluations are proposed for voice professionals or patients with some laryngeal diseases. CONCLUSION: The ELS-UEP consensus for VQ assessment provides clinical statements for the baseline and pre- to post-treatment evaluations of VQ and to improve collaborative research by adopting common and validated VQ evaluation approach.

Utility of fine-needle aspiration biopsy (FNAB) in parotid pleomorphic adenoma diagnosis and management.

PURPOSE: Pleomorphic adenoma (PA), the most common benign tumour of the parotid gland, requires accurate preoperative diagnosis owing to its capacity for malignant transformation. The aim of this study was to evaluate our experience with ultrasound-guided fine-needle aspiration biopsy (FNAB) in the diagnostic algorithm for patients with PA and to assess clinical outcomes for those with different surgical approaches. MATERIAL AND METHODS: We carried out a retrospective analysis of patients treated for parotid gland mass between 2010 and 2016. These had had preoperative FNAB and had undergone subsequent surgery. RESULTS: 165 patients had FNAB with the result of PA and the definitive histology confirmed PA in 159 cases (96.4%). On the other hand, in 179 patients, the definitive histology showed PA and the preoperative FNAB result corresponded in 159 cases (88.9%). The measured sensitivity, specificity and accuracy of ultrasound-guided FNAB in the diagnosis of PA were, respectively, 88.83%, 96.23% and 92.31%. Most of the patients underwent superficial or partial superficial parotidectomy, followed by extracapsular dissection which was associated with statistically lower risk of facial nerve injury (P=0.04). CONCLUSION: Ultrasound-guided FNAB is simple, accurate and valuable in the diagnosis of PA and provides results that can lead to the choice of less invasive operative treatment.

C-reactive protein as an early marker of postoperative leakage in patients after endoscopic laser assisted Zenker's diverticulotomy.

BACKGROUND AND AIM: Minimally invasive endoscopic techniques are the treatment of choice for Zenker's diverticulum (ZD). Our objective was to evaluate the results and efficacy of endoscopic and open approaches, to determine whether postoperative C-reactive protein (CRP) serum levels can be used as a marker to exclude the presence of esophageal leakage, and to identify risk factors for development of postoperative leakage and complications. MATERIALS AND METHODS: Patients who underwent transcervical myotomy and diverticulotomy (TMD) or endoscopic cricopharyngeal myotomy (ECM) with CO2 laser for ZD in years 2008-2021 at our department were included in this retrospective study. RESULTS: Of the 101 patients enrolled, 83 patients underwent ECM and 18 TMD. The procedure time of the endoscopic technique was significantly shorter compared to that of transcervical method (p < 0.001). The median time to oral intake was 6 days for ECM and 10.5 days in the TMD group (p < 0.001). There was a 13% (n = 11) and 16.7% (n = 3) symptomatic recurrence rate and 3.6% (n = 3) and 16.7% (n = 3) major complications rate for ECM and TMD groups, respectively. The incidence of contrast leak (CL) evaluated by postoperative swallow study was 8.9% (9 from 83 patients in the ECM group only). In patients with CL, a significant increase in CRP levels on postoperative day (POD) 2 and 3 was detected when compared to patients without CL. CONCLUSIONS: Endoscopic diverticulotomy with CO2 laser represents a safe and efficient treatment of ZD. Elevation of postoperative CRP serum levels over 123.8 mg/L on POD2 and 98.8 mg/L on POD3 may indicate presence of an esophageal leakage.

Experience with follow-up strategy in selected patients with Warthin tumour diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).

PURPOSE: Warthin tumour (WT) management options comprise surgery or follow-up. The purpose of this study was to asses our experience with the follow-up strategy in selected patients with an ultrasound-guided fine-needle aspiration biopsy (FNAB) showing WT. METHODS: We performed a retrospective analysis of patients diagnosed with WT using FNAB between 1.1.2006 and 31.12.2019. Patients were divided into three groups according to the therapeutic approach-immediate surgery, follow-up or surgery and follow-up. RESULTS: 323 patients were diagnosed with WT and met the study's inclusion criteria (154 women, 47.7% and 169 men, 52.3%). 192 patients were operated right after the diagnosis, 109 patients were observed with their first detected tumour and 22 patients had parotid WT surgery and were in the wait-and-scan protocol with a contralateral tumour, recurrence or both. The growth rate (GR) of observed WT was highly variable (mean GR 1.0 mm/year (5%), median GR 0.8 mm (9%), range - 19.7 to +20.0 mm/year). From 131 patients in the follow-up group, 19 patients underwent surgery and definitive histology revealed 17 WTs and 2 adenocarcinomas. However, these 2 patients had changes in sonographic findings at their next control. The mean observation time was 44.7 months (range 12-138 months) in patients followed exclusively at our institution and 50.9 months (range 12-110 months) in patients observed in cooperation with an otorhinolaryngologist at the patients' place of residence. CONCLUSION: Ultrasound-guided FNAB is an accurate and simple method in WT diagnosis and based on its result a follow-up strategy can be chosen for selected patients with WT.

Text-to-speech synthesis as an alternative communication means after total laryngectomy.

AIMS: Total laryngectomy still plays an essential part in the treatment of laryngeal cancer and loss of voice is the most feared consequence of the surgery. Commonly used rehabilitation methods include esophageal voice, electrolarynx, and implantation of voice prosthesis. In this paper we focus on a new perspective of vocal rehabilitation utilizing alternative and augmentative communication (AAC) methods. METHODS AND PATIENTS: 61 consecutive patients treated by means of total laryngectomy with or w/o voice prosthesis implantation were included in the study. All were offered voice banking and personalized speech synthesis (PSS). They had to voluntarily express their willingness to participate and to prove the ability to use modern electronic communication devices. RESULTS: Of 30 patients fulfilling the study criteria, only 18 completed voice recording sufficient for voice reconstruction and synthesis. Eventually, only 7 patients started to use this AAC technology during the early postoperative period. The frequency and total usage time of the device gradually decreased. Currently, only 6 patients are active users of the technology. CONCLUSION: The influence of communication with the surrounding world on the quality of life of patients after total laryngectomy is unquestionable. The possibility of using the spoken word with the patient's personalized voice is an indisputable advantage. Such a form of voice rehabilitation should be offered to all patients who are deemed eligible.

The role of fine-needle aspiration biopsy (FNAB) in the diagnostic management of parotid gland masses with emphasis on potential pitfalls.

PURPOSE: The treatment strategy of parotid gland tumours depends mainly on the histopathological type of the lesion. Fine-needle aspiration biopsy (FNAB) is recommended in preoperative diagnostics. The aim of the study was to evaluate the FNAB standing in the diagnostic algorithm of parotid gland lesions and to correlate FNAB results in relation to the definitive histopathological diagnosis. MATERIAL AND METHODS: The retrospective analyses of 651 examined and consequently surgically treated parotid gland lesions at the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague between 2006 and 2016 were used. Preoperative cytological results were consequently evaluated in relation to the definitive histopathological diagnosis. RESULTS: The cohort consisted of 367 women and 284 men (average age 58 years). FNAB was diagnostic in 604 (92.8%) patients and non-diagnostic in 47 (7.2%) patients. The result of FNAB was positive (suspicious for malignant tumour) in 89 (14.7%) patients and negative (benign) in 515 (85.3%) patients. Sensitivity of the examination was 80.00%, specificity was 93.82%, PPV 62.92%, NPV 97.28%, and LR + and LR- were 12.95 and 0.21, respectively, with an accuracy of 92.22%. CONCLUSION: Our results confirm the significant role of FNAB in the diagnostic algorithm of parotid gland lesions.

Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors.

This report describes the design, synthesis and evaluation of tumor-targeted polymer probes to visualize epidermal growth factor receptor (EGFR)-positive malignant tumors for successful resection via fluorescence guided endoscopic surgery. Fluorescent polymer probes of various molecular weights enabling passive accumulation in tumors via enhanced permeability and retention were prepared and evaluated, showing an optimal molecular weight of 200,000 g/mol for passive tumor targeting. Moreover, poly(N-(2-hydroxypropyl)methacrylamide)-based copolymers labeled with fluorescent dyes were targeted with the EGFR-binding oligopeptide GE-11 (YHWYGYTPQNVI), human EGF or anti-EGFR monoclonal antibody cetuximab were all able to actively target the surface of EGFR-positive tumor cells. Nanoprobes targeted with GE-11 and cetuximab showed the best targeting profile but differed in their tumor accumulation kinetics. Cetuximab increased tumor accumulation after 15 min, whereas GE 11 needed at least 4 h. Interestingly, after 4 h, there were no significant differences in tumor targeting, indicating the potential of oligopeptide targeting for fluorescence-navigated surgery. In conclusion, fluorescent polymer probes targeted by oligopeptide GE-11 or whole antibody are excellent tools for surgical navigation during oncological surgery of head and neck squamous cell carcinoma, due to their relatively simple design, synthesis and cost, as well as optimal pharmacokinetics and accumulation in tumors.

The FSHR Expression in Head and Neck Squamous Cell Cancer. A Pilot Immunohistochemical Study.

BACKGROUND/AIM: Follicle-stimulating hormone receptor (FSHr), expressed on endothelial cells of vessels in different malignant tumors, has been recently investigated as a potential pan-receptor of cancer treatment. However, the expression of this receptor has also been confirmed in other tissues under pathological conditions including cancer. The aim of the presented pilot study was to evaluate the expression of FSHr in head and neck squamous cancer (HNSCC). PATIENTS AND METHODS: A total of 28 HNSCC patient samples were immunohistochemically analyzed for the presence of FSHr using a commercially available primary antibody. RESULTS: FSHr was detected not only in the tumor tissue, but also in the basal layer or dysplastic parts of squamous mucosa and also in fibroblasts surrounding the tumor tissue. CONCLUSION: FSHr is present on different benign or malignant mesenchymal and epithelial structures in HNSCC. A brief literature review revealed a wider role of FSHr in the development of neoplasia.

Efficacy of Transnasal Flexible Videoendoscopy With Narrow Band Imaging for Follow-Up of Patients After Transoral Laser Cordectomy.

BACKGROUND AND OBJECTIVES: Transoral laser surgery is the optimal surgical treatment modality for the early stages of glottic cancer. To allow for further treatment to be as effective and as minimal as possible, persistent or recurrent tumors should be detected very soon. The main aim is to minimize the risk of necessity of performing a total laryngectomy. Flexible videoendoscopy with narrow band imaging (NBI) was recommended by the European Laryngological Society as a diagnostic method for the follow-up of patients treated for laryngeal cancer. Nevertheless, the efficacy of this technique has not been extensively studied in patients after transoral laser cordectomies for vocal fold cancer. The aim of this study was to evaluate the efficacy of in-office transnasal NBI flexible videoendoscopy in the follow-up of patients after transoral laser cordectomy for glottic cancer. We also focused on describing the specific characteristics of recurrent tumor appearance. MATERIALS AND METHODS: The presented study was conceived as a prospective study. Ninety-four consecutive patients who underwent transoral laser cordectomy for severe dysplasia, Tis, T1, and T2 glottic cancer in the period from June 2010 to August 2015 were enrolled in the study. All patients were postoperatively regularly followed using transnasal videoendoscopic examinations with NBI. Whenever a suspect lesion was identified during in-office examination, its nature was proven histologically. RESULTS: We discovered 23 suspect findings in 21 patients by means of flexible videoendoscopy with NBI. Fifteen (65.2%) of them were histologically confirmed as recurrent tumors, whereas in 8 (34.8%) of them, the recurrent tumor was not proven. In two patients, the recurrent tumor was evident on computed tomography or magnetic resonance imaging, but NBI endoscopy did not reveal relapsing disease. The rest (71 patients) were considered true negative. Of the 15 recurrent tumors detected by NBI-coupled videoendoscopy, 8 (53.3%) were identified as submucosal masses with nonsignificant or no vascular changes, 4 (26.7%) were noted as the progression of leukoplakia without visible vascular changes, only 2 (13.3%) showed typical vascular changes, and, in 1 (6.7%) case, evident, significantly exophytic tumor with pathological vascularization was discovered. The sensitivity, specificity, and positive and negative predictive values of the in-office transnasal videolaryngoscopy with NBI were calculated to be 88%, 92%, 71%, and 97%, respectively. CONCLUSIONS: The results of the study demonstrate that transnasal endoscopy with NBI in an outpatient setting is an excellent method for the follow-up of patients after transoral laser cordectomy for glottic cancer. The method achieves high sensitivity, specificity, and negative predictive value and a slightly low positive predictive value. Nevertheless, we must bear in mind that recurrent tumors after previous endoscopic resection may have a completely different appearance than new tumors originating from previously untreated tissues. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8+ T cells.

BACKGROUND: Standard treatment of oropharyngeal squamous cell carcinoma (OPSCC) is associated with high morbidity, whereas immunotherapeutic approaches using PD-1:PD-L1 checkpoint blockade only show moderate response rates in OPSCC patients. Therefore, a better stratification of patients and the development of novel therapeutic protocols are crucially needed. The importance of tumor-infiltrating B cells (TIL-Bs) in shaping antitumor immunity remains unclear; therefore, we analyzed frequency, phenotype, prognostic value and possible roles of TIL-Bs in OPSCC. METHODS: We utilized transcriptomic analysis of immune response-related genes in 18 OPSCC samples with respect to human papillomavirus (HPV) status. The density and localization of CD20+, CD8+ and DC-LAMP+ cells were subsequently analyzed in 72 tissue sections of primary OPSCC samples in relation to patients' prognosis. The immunohistochemical approach was supplemented by flow cytometry-based analysis of phenotype and functionality of TIL-Bs in freshly resected primary OPSCC tissues. RESULTS: We observed significantly higher expression of B cell-related genes and higher densities of CD20+ B cells in HPV-associated OPSCC samples. Interestingly, CD20+ TIL-Bs and CD8+ T cells formed non-organized aggregates with interacting cells within the tumor tissue. The densities of both intraepithelial CD20+ B cells and B cell/CD8+ T cell interactions showed prognostic significance, which surpassed HPV positivity and CD8+ TIL density in stratification of OPSCC patients. High density of TIL-Bs was associated with an activated B cell phenotype, high CXCL9 production and high levels of tumor-infiltrating CD8+ T cells. Importantly, the abundance of direct B cell/CD8+ T cell interactions positively correlated with the frequency of HPV16-specific CD8+ T cells, whereas the absence of B cells in tumor-derived cell cultures markedly reduced CD8+ T cell survival. CONCLUSIONS: Our results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8+ T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8+ T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8+ T cells in the tumor microenvironment.

The role of fine-needle aspiration biopsy (FNAB) in Warthin tumour diagnosis and management.

PURPOSE: Warthin tumour (WT) is the second most common benign tumour of the parotid gland. The aim of this study was to assess the value of the FNAB in the diagnosis and treatment decision in patients with WT. MATERIALS AND METHODS: We performed a retrospective study of patients treated for parotid gland mass between 2006 and 2016. Patients who underwent the surgery with preoperative FNAB were considered. The first group was comprised of patients with preoperative FNAB showing WT and the second group was formed by patients with definitive histology of WT. RESULTS: 216 patients had FNAB with the result of WT and underwent surgery (98 women-45.4% and 118 men-54.6%). The definitive histology corresponded with the preoperative diagnosis in 201 cases (93.1%). The other way round, 222 patients were operated with definitive histology showing WT and we correlated this finding with preoperative FNAB. The result of FNAB corresponded with definitive histology of WT in 201 cases (90.5%). Counted sensitivity and specificity of the ultrasound-guided FNAB for the diagnosis of WT were, respectively: 96.63% (CI 93.19-98.64%) and 96.21 (CI 93.83-97.86%). The accuracy of this method was 96.36% (CI 94.54-97.70%). CONCLUSION: Ultrasound-guided FNAB is a safe, accurate and important method in WT diagnosis. The therapeutic approach can be chosen based on FNAB results correlated with other clinical findings. We propose that when WT is suspected, follow-up or enucleation of the tumour are appropriate treatments. Patient preferences should be also considered.

Dysfunction of HPV16-specific CD8+ T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1.

BACKGROUND: Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients. METHODS: Tumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3. RESULTS: HPV16-specific tumor-infiltrating T cells were present in 73.1% of HPV-associated oropharyngeal tumors. HPV16 specific CD8+ TILs were able to produce IFNγ upon specific stimulation and predominantly expressed PD-1 but not Tim-3. Specific IFNγ production was further enhanced after a blockade of both PD-1 and Tim-3 pathways but not after a PD-1 blockade alone. Additionally, the specific stimulation of anti-HPV16 CD8+ T cells suppressed Tim-3 upregulation after the PD-1 blockade. CONCLUSION: Our data provide the rationale for combination cancer immunotherapy approaches, including the dual blockade of PD-1 and Tim-3 and, potentially, the use of HPV16-directed therapeutic vaccines.

[Endoscopic optical imaging methods in the diagnostics of the laryngeal cancer]. / Endoskopické optické zobrazovací metody v diagnostice nádoru hrtanu.

Endoscopic optical imaging methods for the detection of mucosal lesions in the ENT area have been developed for better and earlier detection of these changes. They can be divided into horizontal methods group - showing the surface of the mucous membrane (autofluorescence, photodynamic diagnosis, Narrow Band Imaging, magnifying and contact endoscopy) and vertical methods group - visualizing different layers of the mucosa (optical coherence tomography and confocal endomicroscopy). Some of them are routinely used in practice, others are used in experimental mode and their introduction into practice may be a matter of the near future. The authors present a comprehensive overview of available endoscopic optical imaging methods.

Baha implant as a hearing solution for single-sided deafness after retrosigmoid approach for the vestibular schwannoma: surgical results.

Skull base tumors and, in particular, vestibular schwannoma (VS) are among the etiological reasons for single-sided deafness (SSD). Patients with SSD have problems in understanding speech in a noisy environment and cannot localize the direction of sounds. Baha is one of the most frequently used systems for SSD compensation. Out of 38 patients with SSD after retrosigmoid removal of VS who underwent testing with Baha softband, 16 were satisfied and were indicated for Baha implantation. Two surgical approaches have been used-the Nijmegen linear incision technique with subdermal thinning (Group I, implant BI300) and fast surgery technique without subdermal thinning (Group II, implant BIA400). The duration of the surgery, the implant stability measured by Ostell, and skin or soft tissue reactions in long range follow-up were evaluated and compared between Group I and II. There was a difference in duration of surgery, in Group II procedures averaged significantly faster (p > 0.001). In both groups, there was a similar trend of the gradual increase of implant stability. In the Group I and II, there was comparable rate of the skin or soft tissue reactions grade 0, I, II, or III. We have proved Baha to be a suitable possibility for SSD patients after the removal of VS, regardless of the approach. After the retrosigmoid approach to the VS, the key step of Baha implantation must be to reach intact healthy bone to avoid implantation into scar tissue.

Baha implant as a hearing solution for single-sided deafness after retrosigmoid approach for the vestibular schwannoma: audiological results.

Skull base tumors and, in particular, vestibular schwannoma (VS) are among the etiological reasons for single-sided deafness (SSD). Patients with SSD have problems in understanding speech in a noisy environment and cannot localize the direction of sounds. For the majority, this is the handicap for which they try to find a solution. Apart from CROS hearing aids, Baha is one of the most frequently used systems for SSD compensation. 38 patients with single-sided deafness after retrosigmoid removal of a vestibular schwannoma underwent testing with a Baha softband from September 2010 to August 2014. Sixteen patients (42 %) finally decided to accept Baha implantation. Subjective experience with the Baha softband was evaluated by patients using the BBSS questionnaire immediately after testing. Objective evaluation of the effect was performed as a measurement of the sentence discrimination score in noise and side horizontal discrimination without a Baha and 6 weeks and 12 months after a sound processor fitting. There was a significant improvement in sentence discrimination in the 6 week (64.0 %) and 1 year (74.6 %) interval of follow-up in comparison with understanding without Baha (24.0 %, p = 0.001) in situations when sentences are coming from the side of the non-hearing ear and noise contralaterally with SNR -5 dB. Baha can significantly improve sentence discrimination in complex-listening situation in patients with SSD after the VS surgery.

Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma.

Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ+ CD8+ T lymphocytes, IL-17+ CD8+ T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of Cox-2 mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.

The role of narrow band imaging in the detection of recurrent laryngeal and hypopharyngeal cancer after curative radiotherapy.

Narrow band imaging is considered a significant improvement in the possibility of detecting early mucosal lesion of the upper aerodigestive tract. Early detection of mucosal neoplastic lesions is of utmost importance for patients survival. There is evidence that, especially in patients previously treated by means of curative radiotherapy or chemoradiotherapy, the early detection rate of recurrent disease is quite low. The aim of this study was to prove whether the videoendoscopy coupled with NBI might help detect recurrent or secondary tumors of the upper aerodigestive tract. 66 patients previously treated by means of RT or CRT with curative intent were enrolled in the study. All patients underwent transnasal flexible videoendoscopy with NBI mode under local anesthesia. When a suspicious lesion was identified in an ambulatory setting, its nature was proved histologically. Many of these changes were not identifiable by means of conventional white light (WL) endoscopy. The accuracy, sensitivity, specificity, and positive and negative predictive value of the method are very high (88%, 92%, 76%, 96%, and 91%, resp.). Results demonstrate that outpatient transnasal endoscopy with NBI is an excellent method for the follow-up of patients with carcinomas of the larynx and the hypopharynx primarily treated with radiotherapy.

The role of NBI HDTV magnifying endoscopy in the prehistologic diagnosis of laryngeal papillomatosis and spinocellular cancer.

Narrow band imaging (NBI) HDTV (high definition television) magnifying endoscopy is considered to be superior for the accurate display of the microvascular patterns of superficial mucosal lesions. Observation of changes in intraepithelial papillary capillary loops (IPCL) can help distinguish benign from malignant lesions as part of an "optical biopsy." However, IPCL changes in papillomas may be mistaken for spinocellular cancer (SCC). The aim of the study was to determine whether observing microvascular changes alone is sufficient for discriminating between laryngeal SCC and papillomatosis. An additional aim was to identify associated characteristics that could clarify the diagnosis. The study included 109 patients with a suspected laryngeal tumor or papilloma. HDTV NBI magnifying endoscopy was performed during direct laryngoscopy. It was possible to visualize IPCL changes in 82 out of 109 patients (75.2%). In 71 (86.6%) patients, the diagnosis was correctly determined. In 4 (4.9%) cases, the diagnosis of SCC was expressed on the basis of finding pathologic IPCL, but histology did not demonstrate malignancy. To achieve a correct diagnosis using HDTV NBI magnifying endoscopy, it is important not only to observe changes in the shape of IPCL but also to note possible papillary structures with central-axis capillaries typical of papillomatosis.