Michal Zábrodský

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.

Minimally Invasive Video-Assisted versus Minimally Invasive Nonendoscopic Thyroidectomy

Minimally invasive video-assisted thyroidectomy (MIVAT) and minimally invasive nonendoscopic thyroidectomy (MINET) represent well accepted and reproducible techniques developed with the main goal to improve cosmetic outcome, accelerate healing, and increase patients comfort following thyroid surgery. Between 2007 and 2011, a prospective nonrandomized study of patients undergoing minimally invasive thyroid surgery was performed to compare advantages and disadvantages of the two different techniques. There were no significant differences in the length of incision to perform surgical procedures. Mean duration of hemithyroidectomy was comparable in both groups, but it was more time consuming to perform total thyroidectomy by MIVAT. There were more patients undergoing MIVAT procedures without active drainage in the postoperative course and we also could see a trend for less pain in the same group. This was paralleled by statistically significant decreased administration of both opiates and nonopiate analgesics. We encountered two cases of recurrent laryngeal nerve palsies in the MIVAT group only. MIVAT and MINET represent safe and feasible alternative to conventional thyroid surgery in selected cases and this prospective study has shown minimal differences between these two techniques.

Zenker's Diverticulum: Carbon Dioxide Laser Endoscopic Surgery

Nowadays endoscopic diverticulotomy is the surgical approach of the first choice in treatment of Zenkers diverticulum. We report our experience with this procedure and try to sum up recent recommendations for management of surgery and postoperative care. Data of 34 patients with Zenkers diverticulum, treated by endoscopic carbon dioxide laser diverticulotomy at the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University, University Hospital Motol, Prague, Czech Republic, were prospectively stored and followed in relatively short period from May 2009 to December 2013. The average length of diverticulum was 32 mm. The average duration of surgery was 32 min. The patients were fed via feeding tube for 6.1 days and antibiotics were administered for 7 days. Mean hospitalization time was 7.4 days. We observed one transient recurrent laryngeal nerve paralysis and no other serious complications. Recurrence rate was 3%. We recommend complete transection of the diverticular septum in one procedure, systemic antibiotic treatment and exclusion of transoral intake for minimally 5 days, and contrast oesophagogram before resumption of oral intake to exclude fistula. Open diverticulectomy should be reserved for cases with inadequate endoscopic exposure and for revision surgery for multiple recurrences from endoscopic diverticulotomies.

Effectiveness and Side Effects of One-Stage Laser-Assisted Uvuloplasty in Primary Rhonchopathy

The aim of this study is to evaluate the results of laser-assisted uvuloplasty (LAUP) in terms of effect on snoring and side effects. The case report study is based on the analysis of questionnaires with a visual analog scale (VAS) describing the severity of snoring before and 6–26 months after operation and questions regarding postoperative course. The group of patients consisted of 73 patients with primary rhonchopathy. The average preoperative VAS score was 8.36; it decreased to an average of 3.98 postoperatively (p = 0.001). No improvement was reported by 12% of patients, improvement of 4 and more of the VAS scale was reported by 67% of patients. The majority (58%) of patients reported postoperative pain for up to 10 days. Bothersome sensations persisted in 15% of patients. No predictive factors for the success of treatment were found. LAUP diminished snoring in 88% of patients. A major drawback was the postoperative pain. Further studies looking for predictive factors are needed.

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.

Lasers in otorhinolaryngology (ORL) and head and neck surgery

Abstract: The CO2 laser was first used for surgery of the larynx in the 1970s. The introduction of lasers in otorhinolaryngology and head and neck surgery offers patients new ways of disease management. It improves traditional surgical techniques, and expands their scope. Outcomes of laser surgery have improved in association with advances in laser technology and improvements in delivery systems. Nowadays we use several laser systems in many other areas of head and neck surgery. This chapter represents a state-of-the-art update on the use of lasers in otology, in rhinology and for benign and malignant lesions of the larynx and hypopharynx.