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1.
BMJ Case Rep ; 17(2)2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38359957

ABSTRACT

A young male patient presented with an incidental finding of a large supraglottic vascular lesion. The lesion was initially noted during intubation 4 years ago. Although originally listed for elective excision, there was a significant delay and at the time of surgery, the lesion proved too large to remove and a significant threat to the patient's airway. An emergency tracheostomy was performed, followed by two consecutive treatments with sclerotherapy agents to reduce the size of the lesion. It was then successfully excised using a Thunderbeat ultrasound and bipolar dissection and cautery device.


Subject(s)
Sclerotherapy , Vascular Malformations , Humans , Male , Vascular Malformations/diagnostic imaging , Vascular Malformations/therapy
2.
Clin Endocrinol (Oxf) ; 99(3): 233-245, 2023 09.
Article in English | MEDLINE | ID: mdl-37272391

ABSTRACT

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.


Subject(s)
Adenoma , Hyperparathyroidism, Primary , Parathyroid Neoplasms , Humans , Positron Emission Tomography Computed Tomography , Hyperparathyroidism, Primary/diagnostic imaging , Hyperparathyroidism, Primary/etiology , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/complications , Retrospective Studies , Cohort Studies , Adenoma/diagnosis , Adenoma/diagnostic imaging , Methionine , Technetium Tc 99m Sestamibi , Racemethionine , United Kingdom , Parathyroid Glands
3.
Head Neck ; 45(3): 706-720, 2023 03.
Article in English | MEDLINE | ID: mdl-36563301

ABSTRACT

Intrathyroidal parathyroid adenomas (IPAs) are a rare cause of primary hyperparathyroidism. They are often difficult to localize preoperatively and intraoperatively, making diagnosis and treatment challenging. Current data on IPAs are sparse and fragmented in the literature. This makes it difficult to compare the effectiveness of different imaging and surgical techniques. To address this issue, this scoping review maps the literature on IPAs, focusing on four domains: clinical presentation, current localization methods, different surgical techniques, and histopathological features. A search of MEDLINE, Embase, and the Cochrane Library was conducted, with 19 studies meeting the inclusion criteria. The characteristics of IPAs on ultrasound, fine-needle aspiration, CT, MRI, sestamibi-based techniques, and selective venous sampling are summarized. Emerging imaging modalities, including autofluorescence, are introduced. Surgical methods and intraoperative factors that correlate with high success rates for removal are highlighted. This review also identifies gaps in knowledge to guide further research into this area.


Subject(s)
Adenoma , Parathyroid Neoplasms , Humans , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/surgery , Parathyroid Glands/pathology , Diagnostic Imaging , Radiopharmaceuticals , Ultrasonography , Adenoma/diagnostic imaging , Adenoma/surgery , Adenoma/pathology , Technetium Tc 99m Sestamibi
4.
Sci Rep ; 12(1): 20776, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36456616

ABSTRACT

This review aimed to examine the relationship between TP53 mutational status, as determined by genomic sequencing, and survival in squamous cell carcinoma of the head and neck. The databases Medline, Embase, Web of Science (core collection), Scopus and Cochrane Library were searched from inception to April 2021 for studies assessing P53 status and survival. Qualitative analysis was carried out using the REMARK criteria. A meta-analyses was performed and statistical analysis was carried out to test the stability and reliability of results. Twenty-five studies met the inclusion criteria, of which fifteen provided enough data for quantitative evaluation. TP53 mutation was associated with worse overall survival (HR 1.75 [95% CI 1.45-2.10], p < 0.001), disease-specific survival (HR 4.23 [95% CI 1.19-15.06], p = 0.03), and disease-free survival (HR 1.80 [95% CI 1.28-2.53], p < 0.001). Qualitative assessment identified room for improvement and the pooled analysis of all anatomical subsites leads to heterogeneity that may erode the validity of the observed overall effect and its subsequent extrapolation and application to individual patients. Our systematic review and meta-analysis supports the utility of TP53 mutational as a prognostic factor for survival in head and neck squamous cell carcinoma. A well designed prospective, multi-centre trial is needed to definitively answer this question.


Subject(s)
Head and Neck Neoplasms , Tumor Suppressor Protein p53 , Humans , Tumor Suppressor Protein p53/genetics , Prospective Studies , Reproducibility of Results , Head and Neck Neoplasms/genetics , Squamous Cell Carcinoma of Head and Neck/genetics
5.
Eur Arch Otorhinolaryngol ; 279(12): 5573-5581, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35562514

ABSTRACT

PURPOSE: Primary: To determine the rate of occult cervical metastases in primary temporal bone squamous cell carcinomas (TBSSC). Secondary: to perform a subgroup meta-analysis of the risk of occult metastases based on the clinical stage of the tumour and its risk based on corresponding levels of the neck. METHODS: A systematic review and meta-analysis of papers searched through Medline, Cochrane, Embase, Scopus and Web of Science up to November 2021 to determine the pooled rate of occult lymph node/parotid metastases. Quality assessment of the included studies was assessed through the Newcastle-Ottawa scale. RESULTS: Overall, 13 out of 3301 screened studies met the inclusion criteria, for a total of 1120 patients of which 550 had TBSCC. Out of the 267 patients who underwent a neck dissection, 33 had positive lymph nodes giving a pooled rate of occult metastases of 14% (95% CI 10-19%). Occult metastases rate varied according to Modified Pittsburg staging system, being 0% (0-16%) among 12 pT1, 7% (2-20%) among 43 pT2 cases, 21% (11-38%) among 45 pT3, and 18% (11-27%) among 102 pT4 cases. Data available showed that most of the positive nodes were in Level II. CONCLUSION: The rate of occult cervical metastases in TBSCC increases with pathological T category with majority of nodal disease found in level II of the neck.


Subject(s)
Carcinoma, Squamous Cell , Neck Dissection , Humans , Prevalence , Retrospective Studies , Carcinoma, Squamous Cell/pathology , Lymphatic Metastasis , Temporal Bone/pathology , Neoplasm Staging
7.
J Clin Endocrinol Metab ; 107(6): 1706-1713, 2022 05 17.
Article in English | MEDLINE | ID: mdl-35150267

ABSTRACT

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia driven by excess parathyroid hormone (PTH) secretion. PHPT is a common endocrine condition with a prevalence of 1 to 7 cases per 1000 adults. PHPT typically presents in the fifth or sixth decade and shows significant female preponderance. Solitary hyperfunctioning parathyroid adenomas account for 85% to 90% of PHPT cases. The remaining 10% to 15% include cases of multiglandular disease (multiple adenomas or hyperplasia) and, rarely, parathyroid carcinoma (1%). Ectopic parathyroid adenomas may arise due to abnormal embryological migration of the parathyroid glands and can be difficult to localize preoperatively, making surgical cure challenging on the first attempt. The potential existence of multiglandular disease should be considered in all patients in whom preoperative localization fails to identify a target adenoma or following unsuccessful parathyroidectomy. Risk factors for multiglandular disease include underlying genetic syndromes (eg, MEN1/2A), lithium therapy, or previous radiotherapy. In addition to multifocal disease, the possibility of an ectopic parathyroid gland should also be considered in patients requiring repeat parathyroid surgery. In this article, we use illustrative clinical vignettes to discuss the approach to a patient with primary hyperparathyroidism (PHPT) and a suspected ectopic parathyroid adenoma.


Subject(s)
Adenoma , Hyperparathyroidism, Primary , Parathyroid Neoplasms , Adenoma/complications , Adenoma/diagnosis , Adenoma/surgery , Adult , Female , Humans , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/diagnosis , Parathyroid Glands/surgery , Parathyroid Hormone , Parathyroid Neoplasms/complications , Parathyroid Neoplasms/diagnosis , Parathyroid Neoplasms/surgery , Parathyroidectomy/adverse effects
8.
Nat Rev Clin Oncol ; 19(5): 306-327, 2022 05.
Article in English | MEDLINE | ID: mdl-35105976

ABSTRACT

Human papillomavirus (HPV)-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the UICC/AJCC staging system separates HPV+ OPSCC from its HPV-negative (HPV-) counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment de-intensification as a means to improve quality of life while maintaining acceptable survival outcomes. In addition, owing to the distinct biology of HPV+ OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection. In this Review, we provide a summary of the epidemiology, molecular biology and clinical management of HPV+ OPSCC in an effort to highlight important advances in the field. Ultimately, a need exists for improved understanding of the molecular basis and clinical course of this disease to guide efforts towards early detection and precision care, and to improve patient outcomes.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , Humans , Molecular Epidemiology , Oropharyngeal Neoplasms/epidemiology , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Papillomavirus Infections/genetics , Quality of Life , Squamous Cell Carcinoma of Head and Neck
9.
Cancers (Basel) ; 13(19)2021 Sep 30.
Article in English | MEDLINE | ID: mdl-34638429

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor, most commonly located in the pharyngeal recess and endemic to parts of Asia. It is often detected at a late stage which is associated with poor prognosis (5-year survival rate of 63%). Treatment for this malignancy relies predominantly on radiotherapy and/or systemic chemotherapy, which can be associated with significant morbidity and impaired quality of life. In endemic regions NPC is associated with infection by Epstein-Barr virus (EBV) which was shown to upregulate the somatostatin receptor 2 (SSTR2) cell surface receptor. With recent advances in molecular techniques allowing for an improved understanding of the molecular aetiology of this disease and its relation to SSTR2 expression, we provide a comprehensive and up-to-date overview of this disease and highlight the emergence of SSTR2 as a key tumor biomarker and promising target for imaging and therapy.

10.
Cancers (Basel) ; 13(4)2021 Feb 13.
Article in English | MEDLINE | ID: mdl-33668519

ABSTRACT

OBJECTIVE: It has been suggested that the presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with a better prognosis in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic role of CD4+ and CD8+ TILs in head and neck squamous cell carcinoma (HNSCC). METHODS: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched up to September 2020. This study was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Risk ratios from individual studies were displayed in forest plots and the pooled hazard ratios (HR) of death and corresponding confidence intervals (CI) were calculated according to random-effects models. Risk of bias of the included studies was assessed through the Newcastle-Ottawa scale. RESULTS: 28 studies met the inclusion criteria. Studies conducted on HNSCC subsites combined reported a significant reduction in the risk of death for both high CD4+ (HR: 0.77; 95% CI: 0.65-0.93) and high CD8+ TILs (HR: 0.64; 95% CI: 0.47-0.88). High CD4+ TILs were associated with significantly better overall survival among oropharyngeal HNSCC (HR: 0.52; 95% CI: 0.31-0.89), as well as high CD8+ TILS in Human papillomavirus -ve and +ve cancers (HR: 0.39; 95% CI: 0.16-0.93 and HR: 0.40; 95% CI 0.21-0.76 respectively). CD8+ TILs were also associated with improved survival in hypopharyngeal cancers (HR = 0.43 CI: 0.30-0.63). No significant association emerged for patients with cancer of the oral cavity or larynx. CONCLUSIONS: The findings from this meta-analysis demonstrate the prognostic significance of CD8+ and CD4+ TILs in HNSCC and variation in tumor subsite warrants further focused investigation. We highlight how TILs may serve as predictive biomarkers to risk stratify patients into treatment groups, with applications in immune-checkpoint inhibitors notable areas for further research.

11.
Nat Commun ; 12(1): 117, 2021 01 05.
Article in English | MEDLINE | ID: mdl-33402692

ABSTRACT

Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.


Subject(s)
Epstein-Barr Virus Infections , Gene Expression Regulation, Neoplastic , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Receptors, Somatostatin , Viral Matrix Proteins , Animals , Female , Humans , Male , Mice , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/mortality , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/drug effects , Herpesvirus 4, Human/growth & development , Herpesvirus 4, Human/pathogenicity , Host-Pathogen Interactions/genetics , Lymphatic Metastasis , Mice, Nude , Molecular Targeted Therapy , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/virology , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/virology , NF-kappa B/genetics , NF-kappa B/metabolism , Octreotide/pharmacology , Positron Emission Tomography Computed Tomography , Receptors, Somatostatin/antagonists & inhibitors , Receptors, Somatostatin/genetics , Receptors, Somatostatin/metabolism , Signal Transduction , Survival Analysis , Viral Matrix Proteins/antagonists & inhibitors , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolism , Xenograft Model Antitumor Assays
12.
Eur Arch Otorhinolaryngol ; 278(7): 2225-2228, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32869160

ABSTRACT

BACKGROUND AND AIMS: Squamous cell carcinoma (SCC) of the temporal bone is a rare malignancy accounting for only 0.2% of head and neck cancers. There is currently no clear consensus on staging or common approach to management. It is the aim of this work to provide the readers with a review of the current literature on this malignancy. METHODS: A literature review was performed identifying 16 case series with patient numbers ranging from 12 to 124. A total of 708 patients were included in this review, 67% presented with advanced disease. 578 cases were managed operatively with lateral temporal bone resection, some underwent local resection alone in early stage disease. In all studies radiation therapy was used as an adjunct to some degree. RESULTS: More than half of studies reported 100% either 2-, 3- or 5-year survival for T1 and T2 disease with no nodal involvement. Survival correlated with disease stage and in five studies SCC differentiation was found to be a significant prognostic factor. Post-operative radiotherapy was found to improve survival in only one study. CONCLUSIONS: Temporal bone SCC is a readily treatable malignancy in early stage disease, however late stage disease has a poor prognosis. Differentiation of the SCC and stage of disease at presentation appear to have the greatest influence on 5-year survival rates. Further work is required in both the identification of early stage disease and in the treatment of later T3 and T4 lesions.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Humans , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Rate , Temporal Bone/pathology
13.
Int J Cancer ; 146(8): 2305-2314, 2020 04 15.
Article in English | MEDLINE | ID: mdl-31950498

ABSTRACT

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I-II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5-34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I-III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , CTLA-4 Antigen/antagonists & inhibitors , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Neoplasms/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B7-H1 Antigen/immunology , CTLA-4 Antigen/immunology , Chemoradiotherapy , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Humans , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Neoplasms/immunology , Nivolumab/administration & dosage , Nivolumab/therapeutic use , Programmed Cell Death 1 Receptor/immunology
16.
Laryngoscope ; 129(12): 2721-2726, 2019 12.
Article in English | MEDLINE | ID: mdl-30548865

ABSTRACT

OBJECTIVES/HYPOTHESIS: To present yield of transnasal esophagoscopy (TNE) biopsies of upper aerodigestive tract (UADT) lesions and define the role of TNE as a safe alternative to rigid endoscopy. STUDY DESIGN: Retrospective case series. METHODS: All patients who underwent TNE-guided biopsies attempted over a 2-year period were included. Patients were identified using coding records and outpatient diaries. Demographic data were recorded as well as the histological diagnosis and additional histological diagnostic procedures. RESULTS: During the observation period, 134 TNE-guided procedures were attempted. The procedure could not be completed in 19 patients. There were 102/115 (89%) patients who did not require further interventions for histological diagnosis of the tumor. The most common biopsied area was the larynx (53), followed by the tongue base (29). The most common malignancy was invasive squamous cell carcinoma in 42/115 (36.5%). CONCLUSIONS: The work presented in this article strongly suggests that TNE-guided biopsy is a valuable diagnostic tool for patients suspected of having carcinoma of the UADT. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2721-2726, 2019.


Subject(s)
Biopsy/methods , Esophagoscopy/methods , Head and Neck Neoplasms/pathology , Aged , Female , Humans , Male , Nose , Reproducibility of Results , Retrospective Studies
17.
Cochrane Database Syst Rev ; 12: CD012939, 2018 12 14.
Article in English | MEDLINE | ID: mdl-30550641

ABSTRACT

BACKGROUND: More than 400,000 cases of oropharyngeal squamous cell cancer (OPSCC) are diagnosed every year worldwide and this is rising. Much of the increase has been attributed to human papillomavirus (HPV). HPV-positive OPSCC patients are often younger and have significantly improved survival relative to HPV-negative patients. Traditional management of OPSCC has been with radiotherapy with or without chemotherapy, as this was shown to have similar survival to open surgery but with significantly lower morbidity. Techniques have evolved, however, with the development of computerised planning and intensity-modulated radiotherapy, and of minimally invasive surgical techniques. Acute and late toxicities associated with chemoradiotherapy are a significant burden for OPSCC patients and with an ever-younger cohort, any strategies that could decrease treatment-associated morbidity should be investigated. OBJECTIVES: To assess the effects of de-intensified adjuvant (chemo)radiotherapy in comparison to standard adjuvant (chemo)radiotherapy in patients treated with minimally invasive transoral surgery (transoral robotic surgery or transoral laser microsurgery) for resectable HPV-positive oropharyngeal squamous cell carcinoma. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 26 April 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with carcinoma of the oropharynx (as defined by the World Health Organization classification C09, C10). Cancers included were primary HPV-positive squamous cell tumours originating from the oropharyngeal mucosa. Tumours were classified as T1-4a with or without nodal spread and with no evidence of distant metastatic spread. The intervention was minimally invasive transoral surgery followed by de-intensified adjuvant therapy (either omission of chemotherapy or reduced-dose radiotherapy). The comparator was minimally invasive transoral surgery followed by standard concurrent chemoradiotherapy or standard-dose radiotherapy. The treatments received were of curative intent and patients had not undergone any prior intervention, other than diagnostic biopsy. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related survival was to be studied where possible) and disease-free survival, measured at one, two, three and five years. Our secondary outcomes included assessment of swallowing ability and voice, measured at one, six, 12 and 24 months. We planned to use GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: We did not identify any completed RCTs that met our inclusion criteria. However, three eligible studies are in progress:ADEPT is a phase III trial comparing postoperative radiotherapy with or without cisplatin in HPV-positive T1-4a OPSCC patients. Included patients must have received minimally invasive surgery and demonstrated extra-capsular spread from disease in the neck.ECOG-E3311 is a phase II trial of treatment for HPV-positive locally advanced OPSCC (stages III-IVa + IVb without distant metastasis). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy.PATHOS is a phase III trial of treatment for HPV-positive OPSCC (T1-3, N0-2b). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy. High-risk patients are randomised to radiotherapy with or without concurrent cisplatin. AUTHORS' CONCLUSIONS: This review highlights the current lack of high-quality randomised controlled trials studying treatment de-escalation after minimally invasive surgery in patients with HPV-positive OPSCC. However, trials that will meet the inclusion criteria for this review are in progress with results expected between 2021 and 2023.


Subject(s)
Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/virology , Chemoradiotherapy, Adjuvant/methods , Oropharyngeal Neoplasms/therapy , Oropharyngeal Neoplasms/virology , Papillomaviridae , Carcinoma, Squamous Cell/surgery , Chemoradiotherapy, Adjuvant/standards , Humans , Laser Therapy/methods , Microsurgery/methods , Oropharyngeal Neoplasms/surgery , Radiotherapy Dosage , Robotic Surgical Procedures
18.
Oral Oncol ; 83: 32-37, 2018 08.
Article in English | MEDLINE | ID: mdl-30098776

ABSTRACT

OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression. RESULTS: While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (-) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (-) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (-)/p16-high tumors. CONCLUSIONS: RPPA data suggest high p16 protein expression in many HPV (-) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1.


Subject(s)
Alphapapillomavirus/isolation & purification , Biomarkers, Tumor/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Head and Neck Neoplasms/metabolism , Squamous Cell Carcinoma of Head and Neck/metabolism , Alphapapillomavirus/metabolism , Cohort Studies , Cyclin-Dependent Kinase Inhibitor p16/genetics , G1 Phase , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/virology , Humans , Mutation , Papillomavirus Infections/metabolism , Papillomavirus Infections/virology , S Phase , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/virology , Up-Regulation
19.
BMJ Open ; 8(7): e023339, 2018 07 28.
Article in English | MEDLINE | ID: mdl-30056394

ABSTRACT

OBJECTIVES: To examine the level of awareness of the link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) and epidemiological trends in HPV-related OPC among general practitioners (GPs) in the UK. DESIGN: Cross-sectional survey. PARTICIPANTS: 384 GPs from England, Scotland, Wales and Northern Ireland. SETTING: The survey was administered at GP training courses and via email to lists of training course attendees. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of respondents aware of the link between HPV and OPC; respondents' self-rated knowledge of OPC; proportion of participants aware of the epidemiological trends in HPV-associated OPC. RESULTS: 384 questionnaires were completed with an overall response rate of 72.9%. 74.0% of participants recognised HPV as a risk factor for OPC, which was lower than knowledge about the role of smoking, chewing tobacco and alcohol consumption (all >90% recognition). Overall, 19.4% rated their knowledge of OPC as very good or good, 62.7% as average and 17.7% as poor or very poor. The majority (71.9%) were aware that rates of HPV-associated OPC have increased over the last two decades. Fewer than half (41.5%) of the participants correctly identified being male as a risk factor of HPV-associated OPC, while 58.8% were aware that patients with HPV-associated OPC tend to be younger than those with non-HPV-associated disease. CONCLUSIONS: The association of HPV infection with OPC is a relatively recent discovery. Although the level of awareness of HPV and OPC among GPs was high, the characteristics of HPV-associated OPC were less well recognised, indicating the need for further education.


Subject(s)
Clinical Competence , General Practitioners , Oropharyngeal Neoplasms/epidemiology , Papillomavirus Infections/epidemiology , Squamous Cell Carcinoma of Head and Neck/epidemiology , Age Factors , Alcohol Drinking/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Risk Factors , Sex Factors , Smoking/epidemiology , Surveys and Questionnaires , Tobacco Use/epidemiology , United Kingdom/epidemiology
20.
JAMA Otolaryngol Head Neck Surg ; 144(3): 252-258, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29450472

ABSTRACT

IMPORTANCE: Scuba diving is becoming increasingly popular. However, scuba diving is associated with specific risks; 80% of adults and 85% of juvenile divers (aged 6-17 years) have been reputed to have an ear, nose, or throat complaint related to diving at some point during their diving career. Divers frequently seek advice from primary care physicians, diving physicians, and otorhinolaryngologists, not only in the acute setting, but also related to the long-term effects of diving. OBSERVATIONS: The principles underpinning diving-related injuries that may present to the otorhinolaryngologist rely on gas volume and gas saturation laws, and the prevention of these injuries requires both that the diver is skilled and that their anatomy allows for pressure equalization between the various anatomical compartments. The overlapping symptoms of middle ear barotrauma, inner ear barotrauma, and inner ear decompression sickness can cause a diagnostic conundrum, and a thorough history of both the diver's symptoms and the dive itself are required to elucidate the diagnosis. Correct diagnosis and appropriate treatment result in a more timely return to safe diving. CONCLUSIONS AND RELEVANCE: The aim of this review is to provide a comprehensive overview of otorhinolaryngological complications during diving. With the increasing popularity of diving and the frequency of ear, nose, or throat-related injuries, it could be expected that these injuries will become more common and this review provides a resource for otorhinolaryngologists to diagnose and treat these conditions.


Subject(s)
Diving/adverse effects , Otorhinolaryngologic Diseases/etiology , Barotrauma/etiology , Decompression Sickness/etiology , Epistaxis/etiology , Facial Paralysis/etiology , Humans
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