The effect of smoking, drinking and smoking cessation on morbidity and mortality in oral cancer: a controlled study

14 March 200

Is [F-18]-fluorodeoxy-D-glucose positron emission tomography of value in the management of patients with craniofacial bone sarcomas undergoing neo-adjuvant treatment?

We evaluated the role of 18FDG PET/CT used to assess response to preoperative chemotherapy in patients with primary craniofacial bone sarcomas

Head and neck sarcomas: A single institute series

BACKGROUND: Sarcomas are tumours of mesenchymal origin, accounting for 1% of all malignancies. METHODS: This is a retrospective analysis of 107 head and neck sarcoma cases, treated over a period of thirteen years. RESULTS: Fifty-four patients had with craniofacial bone sarcomas (BSs) (male: 33; female: 21) with high grade osteosarcoma being the most predominant type. The soft tissue sarcomas (STS) (53 patients; male: 28, female: 25) were histologically diverse with rhabdomyosarcomas and myxofibrosarcomas being the predominant types. The majority of BSs were managed with neoadjuvant chemotherapy followed by surgery, whereas in STSs treatment included predominantly surgery followed by radiotherapy. Overall survival estimates were 79% at 2years and 64% at 5years (mean follow-up period was 48months). CONCLUSIONS: The mesenchymal origin of sarcomas, the pattern of disease spread and the different extent of cancellous bone infiltration in contrast to epithelial tumours, dictate distinct principles for surgical clearance

Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.

BACKGROUND: Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach. METHODS: Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings. RESULTS: HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors. CONCLUSION: These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV negative disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT and mTOR inhibitors in HNSCC

Cardiopulmonary exercise testing and cardiopulmonary morbidity in patients undergoing major head and neck surgery

Cardiopulmonary exercise testing (CPET) is used as a risk stratification tool for patients undergoing major surgery. In this study, we investigated the role of CPET in predicting day five cardiopulmonary morbidity in patients undergoing head and neck surgery. This observational cohort study included 230 adults. We recorded preoperative CPET variables and day five postoperative cardiopulmonary morbidity. Full data from 187 patients were analysed; 43 patients either had incomplete data sets or declined surgery/CPET. One hundred and nineteen patients (63.6%) developed cardiopulmonary morbidity at day five. Increased preoperative heart rate and duration of surgery were independently associated with day five cardiopulmonary morbidity. Those with such morbidity also had lower peak V̇O2 11.4 (IQR 8.4-18.0) vs 16.0 (IQR 14.0-19.7) ml.kg-1.min-1, P<0.0001 and V̇O2 at AT 10.6 (IQR 9.1-13.1) vs 11.5 (IQR 10.5-13.0) ml.kg-1.min-1, p=0.03. Logistic regression model containing peak V̇O2 and duration of surgery demonstrated that increased peak V̇O2 was associated with a reduction in the likelihood of cardiopulmonary complications OR 0.92 (95%CI 0.87 to 0.96), p=0.001. The area under the receiver operating characteristic curve for this model was 0.75(95%CI 0.68 to 0.82), p<0.0001, 64% sensitivity, 81% specificity. CPET can help to predict day five cardiopulmonary morbidity in the patients undergoing head and neck surgery. A model containing peak V̇O2 allowed identification of those with such complications

Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort

BACKGROUND: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. // METHODS: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. // RESULTS: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001). // CONCLUSION: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. // CLINICAL TRIAL REGISTRATION: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.

ABSTRACT: BACKGROUND: Human Papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological entity compared with HPV negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA methylation analysis. METHODS: Using laser-capture microdissection of 42 formalin-fixed paraffin-embedded (FFPE) HNSCCs, we generated DNA methylation profiles of 18 HPV+ and 14 HPV- samples, using the Infinium 450k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh frozen and cell lines) using two independent methods (Infinium 450k and whole-genome MeDIP-seq). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7) and effects on methylation were assayed using the Infinium 450k technology. RESULTS AND DISCUSSION: Unsupervised clustering over the most methylation variable positions (MVPs) showed that samples segregated according to HPV status, but also that HPV+ tumours are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG Island Methylator Phenotype in a sub-group of the HPV+ tumours. Supervised analysis revealed a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancer confirmed the observed DNA methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions (DMRs) identified 43 hypermethylated promoter DMRs, including for three Cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the Cadherin gene family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature observed in HPV+ HNSCC tumours and established E6 as the main viral effector gene. CONCLUSIONS: Our data establish archival FFPE tissue to be highly suitable for this type of methylome analysis and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as Cadherins which are implicated in tumour progression and metastasis

Mouth cancer: presentation, detection and referral in primary dental care

Mouth cancer can present as a variety of abnormalities and visible changes affecting the oral mucosa, including ulceration, swelling and areas of erythema. The five-year survival from mouth cancer is poor at approximately 50%. Detection of the cancer while less than 2 cm in diameter with no metastasis greatly improves the outcome for the patient. Although many cancers in the mouth develop from what was previously an apparently normal mucosa, some arise in pre-existing conditions that are therefore regarded as potentially malignant. Regular assessment of the soft tissues within the mouth and the neck for the presence of abnormalities is an essential component of primary dental care. Any persistent and unexplained abnormality requires referral for definitive diagnosis and specialist management

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks