Purpose: This study examines the tumour-host immune interactions in head and neck squamous cell carcinoma (HNSCC) and their relationship to human papillomavirus (HPV) infectivity and patient survival.
Methods: The adaptive and innate immune profile of surgical tumour specimens obtained from HNSCC patients was determined using qRT-PCR and immunohistochemistry. Intratumoural and invading margin leukocyte populations (CD3, CD8, CD16, CD20, CD68, FoxP3 and HLA-DR) were quantified and compared with patient disease-specific survival. Additionally, the expression of 41 immune activation- and suppression-related genes was evaluated in the tumour microenvironment. Tumour cells were also assessed for expression of HLA-A, HLA-G and HLA-DR. HPV infectivity of tumour biopsies was determined using HPV consensus primers (MY09/MY11 and GP5+/GP6+) and confirmed with p16 immunohistochemistry.
Results: HPV+ patient samples showed a significantly increased infiltration by intratumoural CD20+ B cells, as well as by invasive margin FoxP3+Treg, compared with HPV- patient samples. There was also a trend towards increased intratumoural CD8+ T cells and HLA-G expression on tumour cells in HPV+ samples. qRT-PCR data demonstrated a general pattern of increased immune activation and suppression mechanisms in HPV+ samples. Additionally, a combined score of intratumoural and invasive margin FoxP3 infiltration was significantly associated with disease-specific survival (P < 0.05).
Conclusions: These data demonstrate significant differences in the immune cell profile of HPV+ and HPV- HNSCC. This study identifies several possible targets for immunotherapy and possible prognostic markers (FoxP3 and HLA-G) that may be specific to HNSCC.
Background: To examine the effect of the natural antimicrobial peptide human β-defensin-3 (hBD-3), on the migration of a head and neck cancer cell line in vitro using microfabrication and soft-lithographic techniques.
Methods: TR146 cancer cells were seeded in Petri dishes with microfabricated wells for cell migration assays. Total 54 cell islands were used of various shape and size and experimental media type. Cell migration assays were analyzed in six group media: Dulbecco's modified medium (DMEM); DMEM with vascular endothelial growth factor (VEGF); Conditioned media of human embryonic kidney cells (HEK 239) expressing hBD-3 via transfected cloned pcDNA3 as CM/hBD-3; CM/hBD-3+ VEGF; conditioned medium from non-transfected HEK 239 (not expressing hBD-3) as control (CM); and the last group was CM + VEGF. Cell islands were circular or square and varied in size (0.25 mm(2), 0.125 mm(2), and 0.0625 mm(2)). Cell islands were imaged at t=0 h, 3 h, 6 h, and 24 h.
Results: The results show cancer cell islands that originally were smaller had higher migration indices. There was no difference of MIs between circular and square cell islands. MIs at the end point were significantly different among the groups except between CM and CM-hBD-3+ VEGF.
Conclusions: VEGF enhanced cancer cell migration. The combination of DMEM and VEGF showed a synergistic effect on this phenomenon of cancer cell migration. Conditioned medium with hBD-3 suppressed cancer cell migration. hBD-3 suppressed VEGF enhancement of TR146 cancer cell migration.
Background: Oral epithelial dysplasia (OED) has a malignant potential. Therapeutic options for OED remain both limited and without good evidence. Despite surgery being the most common method of treating OED, recurrence and potentially significant morbidity remain problematic. Consequently, there has been much interest in non-surgical treatments for OED. Cyclo-oxygenase (COX) up-regulation is known to occur in the dysplasia-carcinoma sequence and evidence now exists that COX-2 is a prognostic marker of malignant transformation in OED. COX-inhibitors are therefore considered a potential therapeutic strategy for treating this condition. We aimed to provide both proof of principal evidence supporting the effect of topical COX inhibition, and determine the feasibility of recruitment to an OED chemoprevention trial in the UK.
Methods: Recruitment of 40 patients with oral leukoplakia to 4 study arms was planned. The total daily dose of Aspirin would increase in each group and be used in the period between initial diagnostic and follow-up biopsies.
Results: During the 15-month recruitment period, 15/50 screened patients were eligible for recruitment, and 13 (87%) consented. Only 1 had OED diagnosed on biopsy. 16 patients were intolerant of, or already taking Aspirin and 16 patients required no biopsy. Initial recruitment was slow, as detection relied on clinicians identifying potentially eligible patients. Pre-screening new patient letters and directly contacting patients listed for biopsies improved screening of potentially eligible patients. However, as the incidence of OED was so low, it had little impact on trial recruitment. The trial was terminated, as recruitment was unlikely to be achieved in a single centre.
Conclusion: This feasibility trial has demonstrated the low incidence of OED in the UK and the difficulties in conducting a study because of this. With an incidence of around 1.5/100,000/year and a high proportion of those patients already taking or intolerant of Aspirin, a large multi-centred trial would be required to fulfil the recruitment for this study. The ability of topical non-steroidal anti-inflammatory drugs to modify COX and prostaglandin expression remains an important but unanswered question. Collaboration with centres in other parts of the world with higher incidences of the disease may be required to ensure adequate recruitment. ISRCTN: 31503555.
Background: Thyroid carcinoma generally responds well to treatment and spinal metastasis is an uncommon feature. Many studies have looked at the management of spinal metastasis and proposed treatments, plans and algorithms. These range from well-established methods to potentially novel alternatives including bisphosphonates and vascular endothelial growth factor (VEGF) therapy, amongst others.The purposes of this systematic review of the literature are twofold. Firstly we sought to analyse the proposed management options in the literature. Then, secondly, we endeavoured to make recommendations that might improve the prognosis of patients with spinal metastasis from thyroid carcinomas.
Methods: We conducted an extensive electronic literature review regarding the management of spinal metastasis of thyroid cancer.
Results: We found that there is a tangible lack of studies specifically analysing the management of spinal metastasis in thyroid cancer. Our results show that there are palliative and curative options in the management of spinal metastasis, in the forms of radioiodine ablation, surgery, selective embolisation, bisphosphonates and more recently the VEGF receptor targets.
Conclusions: The management of spinal metastasis from thyroid cancer should be multi-disciplinary. There is an absence; it seems, of a definitive protocol for treatment. Research shows increased survival with 131I avidity and complete bone metastasis resection. Early detection and treatment therefore are crucial. Studies suggest in those patients below the age of 45 years that treatment should be aggressive, and aim for cure. In those patients in whom curative treatment is not an option, palliative treatments are available.
Objectives: Secondary malignancy in the oral mucosa is recognized as one of the most serious complications in patients who received allogenic hematopoietic stem cell transplantation (HSCT). However, potential risk factors associated with carcinogenesis after HSCT that have been reported remain elusive. We experienced a rare case of secondary malignancies of the oral and esophageal mucosa and analyzed the expression of tumor suppressor gene product p16.
Case report: A 35-year-old male had malignant lesions of the oral and esophageal mucosa two years after HSCT. Partial maxillectomy and endoscopic submucosal dissection were performed. Immunohistochemical analyses revealed that the tumor cells of malignant and premalignant lesions of the oral cavity and esophagus but not keratosis were positive for p16.
Conclusions: Pathological examinations with p16 immunohistochemistry may contribute to an early diagnosis of secondary malignancy after HSCT.
As a result of major ablative surgery, head and neck oncology patients can be left with significant defects in the orofacial region. The resultant defect raises the need for advanced reconstruction techniques. The reconstruction in this region is aimed at restoring function and facial contour. The use of vascularised free flaps has revolutionised the reconstruction in the head and neck. Advances in reconstruction techniques have resulted in continuous improvement of oral rehabilitation. For example, endosteal implants are being used to restore the masticatory function by the way of prosthetic replacement of the dentition. Implant rehabilitation usually leads to improved facial appearance, function, restoration of speech and mastication. Suitable dental implant placement's site requires satisfactory width, height and quality of bone. Reconstruction of hard tissue defects therefore will need to be tailored to meet the needs for implant placement.The aim of this feasibility study was to assess the compatibility of five standard commercially available dental implant systems (Biomet 3i, Nobel Biocare, Astra tech, Straumann and Ankylos) for placement into vascularised fibula graft during the reconstruction of oromandibular region.Radiographs (2D) of the lower extremities from 142 patients in the archives of the Department of Radiology in University College London Hospitals (UCLH) were analysed in this study. These radiographs were from 61 females and 81 males. Additionally, 60 unsexed dry fibular bones, 30 right sided, acquired from the collection of the Department of Anatomy, University College London (UCL) were also measured to account for the 3D factor.In the right fibula (dry bone), 90% of the samples measured had a width of 13.1 mm. While in the left fibula (dry bone), 90% of the samples measured had a width of 13.3 mm. Fibulas measured on radiographs had a width of 14.3 mm in 90% of the samples. The length ranges of the dental implants used in this study were: 7-13 mm (Biomet 3i), 10-13 mm (Nobel biocare), 8-13 mm (Astra Tech), 8-12 mm (Straumann ) and 8-11 mm (Ankylos).This study reached a conclusion that the width of fibula is sufficient for placement of most frequently used dental implants for oral rehabilitation after mandibular reconstructive procedures.
Background: The incidence of head and neck cancer is relatively low in developed countries and highest in South East Asia. Notwithstanding advances in surgery and radiotherapy over the past several decades, the 5-year survival rate for head and neck cancer has stagnated and remains at 50-55%. This is due, in large part, to both regional and distant disease spread, including spinal metastasis. Spinal metastasis from head and neck cancer is rare, has a poor prognosis and can significantly impede end-stage quality of life; normally only palliative care is given.This study aims to conduct a systematic review of the evidence available on management of spinal metastasis from head and neck cancer and to use such evidence to draw up guiding principles in the management of the distant spread.
Methods: Systematic review of the electronic literature was conducted regarding the management of spinal metastasis of head and neck malignancies.
Results: Due to the exceptional rarity of head and neck cancers metastasizing to the spine, there is a paucity of good randomized controlled trials into the management of spinal metastasis. This review produced only 12 case studies/reports and 2 small retrospective cohort studies that lacked appropriate controls.
Conclusion: Management should aim to improve end-stage quality of life and maintain neurological function. This review has found that radiotherapy +/- medical adjuvant is considered the principle treatment of spinal metastasis of head and neck cancers.There is an absence of a definitive treatment protocol for head and neck cancer spinal metastasis. Our failure to find and cite high-quality scientific evidence only serves to stress the need for good quality research in this area.