Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection.

Influenza A virus (IAV) infection constitutes an annual health burden across the globe. Plasmacytoid dendritic cells (PDCs) are central in antiviral defense because of their superior capacity to produce type I IFNs in response to viruses. Dendritic cells (DCs) differ depending on their anatomical location. However, only limited host-pathogen data are available from the initial site of infection in humans. In this study, we investigated how human tonsil PDCs, likely exposed to virus because of their location, responded to IAV infection compared with peripheral blood PDCs. In tonsils, unlike in blood, PDCs are the most frequent DC subset. Both tonsil and blood PDCs expressed several genes necessary for pathogen recognition and immune response, generally in a similar pattern. MxA, a protein that renders cells resistant to IAV infection, was detected in both tonsil and blood PDCs. However, despite steady-state MxA expression and contrary to previous reports, at high IAV concentrations (typically cytopathic to other immune cells), both tonsil and blood PDCs supported IAV infection. IAV exposure resulted in PDC maturation by upregulation of CD86 expression and IFN-α secretion. Interestingly, blood PDCs secreted 10-fold more IFN-α in response to IAV compared with tonsil PDCs. Tonsil PDCs also had a dampened cytokine response to purified TLR ligands compared with blood PDCs. Our findings suggest that tonsil PDCs may be less responsive to IAV than blood PDCs, highlighting the importance of studying immune cells at their proposed site of function.

Trismus in patients with head and neck cancer and 5-year overall survival.

BACKGROUND: Trismus is a common complication of radiotherapy for head and neck cancer but its impact on survival is unknown. AIMS/OBJECTIVES: This prospective study evaluates the incidence of trismus in patients with head and neck cancer receiving radiotherapy and the impact of trismus on 5-year overall survival. MATERIAL AND METHODS: Two hundred forty-four patients with head and neck cancer were included. All patients received instructions on jaw exercises and were evaluated before initiation of radiotherapy and at 2, 6, and 12 months after termination of radiotherapy. RESULTS: One year after treatment 25% had a reduced maximum interincisal opening (MIO) of 13 mm or more as compared to the pretreatment MIO. Trismus was most prevalent in patients with oral and oropharyngeal cancer. A trend towards worse 5-year overall survival was seen among patients with trismus. CONCLUSIONS: The trismus rate was approximately 30% at 12 months. Jaw exercises should primarily be offered to patients with oral and oropharyngeal cancer who are most likely to benefit. Further studies are required to investigate the effect of trismus on survival. SIGNIFICANCE: This study identifies patients likely to benefit from jaw exercises and provides basis for further research on trismus and survival.

Human papillomavirus prevalence in mouthwashes of patients undergoing tonsillectomy shows dominance of HPV69, without the corresponding finding in the tonsils.

BACKGROUND: The role of human papillomavirus (HPV) in tonsillar squamous cell carcinomas (TSCC) is of interest, since a considerable proportion of TSCC in Sweden and other Western countries is HPV positive. Nevertheless, the natural history of HPV in normal tonsils, and the progression from localized infection to pre-malignant lesion to cancer are poorly understood. The aim of this study was to investigate whether HPV types found in mouthwash samples correlated to those in tonsillar tissue from the same individuals undergoing tonsillectomy. METHODS: Mouthwash samples from 232 patients, aged 3-56 years, undergoing tonsillectomy, the majority with chronic tonsillitis, were collected at the time of surgery and analysed for the presence of 27 HPV types by a bead based multiplex assay. RESULTS: An HPV prevalence of 10.3% (24/232) was observed in mouthwash samples, with HPV 69 being the dominant type (10/24). Ten patients were positive for high risk HPV (HPV 16, 33, 35, 45, 56, 59). None of the tonsils resected from patients with HPV-positive mouthwash samples were positive for HPV. CONCLUSIONS: Despite an oral HPV prevalence of 10.3% in mouthwash samples from tonsillectomized patients, with dominance of HPV 69, none of the corresponding tonsillar samples exhibited the presence of HPV.

Morbidity of supraomohyoidal and modified radical neck dissection combined with radiotherapy for head and neck cancer: a prospective longitudinal study.

BACKGROUND: The purpose of this study was to show the investigated impact of supraomohyoidal neck dissection and modified radical neck dissection, both combined with radiotherapy, on cervical range of motion (CROM), mouth opening, swallowing, lymphedema, and shoulder function. METHODS: One hundred eight patients who had neck dissections and 98 patients who had non-neck dissections were evaluated in a prospective, nonselective, longitudinal cohort study by a physiotherapist and a speech-language pathologist (SLP) before the start of radiotherapy and up to 12 months after treatment. RESULTS: The incidence of shoulder disability after neck dissection was 18%. Supraomohyoidal neck dissection had no significant effect on the evaluated parameters at any time point. Modified radical neck dissection significantly reduced CROM and mouth opening 2 months after treatment, but after 12 months only cervical rotation was still significantly reduced. CONCLUSION: In patients treated with external beam radiation (EBRT), modified radical neck dissection induced additional morbidity regarding CROM but not regarding mouth opening, swallowing, and lymphedema 1 year after treatment. Both modified radical neck dissection and supraomohyoidal neck dissection induced shoulder disability.

Early self-care rehabilitation of head and neck cancer patients.

CONCLUSIONS: No positive effects of early preventive rehabilitation could be identified. The results do not contradict the proposition that rehabilitation based on self-care can be effective but it is important to establish evidence-based training programs and identify proper instruments for selection of patients and evaluation of intervention. OBJECTIVES: Patients with head and neck cancer suffer from functional impairments due to intense treatment. In this study, we investigated the effectiveness of an experimental early preventive rehabilitation using hard, objective end points in a nonselective, longitudinal, prospective cohort study. METHODS: In all, 190 patients were included in the program and received instructions for training before the start of treatment with the aim of reducing swallowing problems and reducing mouth opening and stiffness in the neck. A control group of 184 patients was recruited. RESULTS: There was no difference in weight loss and 2-year survival between the two groups. No positive effects concerning functional impairments were found in patient-reported outcome measures.

Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy.

BACKGROUND AND PURPOSE: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck. MATERIAL AND METHODS: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model. RESULTS: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D(50)=61.5 Gy (52.9-84.9 Gy), γ=1.4 (0.8-2.6) and s=0.1 (0.01-0.3). CONCLUSIONS: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.

Esophageal stricture after radiotherapy in patients with head and neck cancer: experience of a single institution over 2 treatment periods.

BACKGROUND: Risk factors for development of a stricture of the upper esophagus after radiotherapy for head and neck cancer are poorly defined. METHODS: This was a retrospective case-control study of patients diagnosed and treated for esophageal stricture after radiotherapy for head and neck cancer. RESULTS: The incidence of esophageal stricture after external beam radiation therapy (EBRT) was 3.3%. Seventy patients with stricture and 66 patients without stricture were identified. A multivariate analysis showed that there was increased risk of stricture in receiving enteral feeding during EBRT or in receiving a mean dose of >45 Gy to the upper esophagus. CONCLUSIONS: Enteral feeding during EBRT is strongly associated with the development of stricture of the esophagus, as is a mean dose of >45 Gy to the upper esophagus. Treatment of the stricture with Savary-Gilliard bougienage or through scope balloon dilatation is safe and successful but often has to be repeated.

Clinical outcome following radiotherapy and planned neck dissection in N+ head and neck cancer patients.

CONCLUSIONS: This study confirms earlier findings that patients with viable tumour cells in the neck after external beam radiotherapy (EBRT) have a poor prognosis. The study also indicates that neck dissection (ND) does not change the prognosis for patients with a complete clinical response in the neck. At the moment our guidelines concerning this matter are being reviewed. OBJECTIVES: The protocol at our institution stipulates a planned ND in patients with metastasis in the neck after EBRT regardless of the response in the neck. As the necessity for a planned ND has not been clarified we wanted to evaluate our results. PATIENTS AND METHODS: Patients diagnosed from 1998 to 2002 with metastasis in the neck who received EBRT were evaluated for histopathological findings and clinical outcome. RESULTS: A total of 156 patients were included. Overall survival was 62% and disease-specific survival was 76%. There was a complete response (CR) in the neck in 63 patients (40%); among these 15 had viable tumour cells in the neck. In patients not achieving CR, 40% (37/93) had viable tumour cells left in the neck. Patients with viable tumour cells in the neck after EBRT had disease-specific survival of 48% compared with 90% among patients without viable tumour cells.