Head and neck squamous cell carcinomas (HNSCCs) are an aggressive, genetically complex and difficult to treat group of cancers. In lieu of truly effective targeted therapies, surgery and radiotherapy ...represent the primary treatment options for most patients. But these treatments are associated with significant morbidity and a reduction in quality of life. Resistance to both radiotherapy and the only available targeted therapy, and subsequent relapse are common. Research has therefore focussed on identifying biomarkers to stratify patients into clinically meaningful groups and to develop more effective targeted therapies. However, as we are now discovering, the poor response to therapy and aggressive nature of HNSCCs is not only affected by the complex alterations in intracellular signalling pathways but is also heavily influenced by the behaviour of the extracellular microenvironment. The HNSCC tumour landscape is an environment permissive of these tumours' aggressive nature, fostered by the actions of the immune system, the response to tumour hypoxia and the influence of the microbiome. Solving these challenges now rests on expanding our knowledge of these areas, in parallel with a greater understanding of the molecular biology of HNSCC subtypes. This update aims to build on our earlier 2014 review by bringing up to date our understanding of the molecular biology of HNSCCs and provide insights into areas of ongoing research and perspectives for the future.
Background: The interactions of genetic and environmental factors may account for the variability in the expression of malocclusion. The study of malocclusion etiology is fundamental to understand ...the biology underlying craniofacial growth and dental relations. Understanding biology will improve progress toward effective treatment and prevention, thereby decreasing the burden of this condition. Aims: The present study was set out to investigate the association of the single nucleotide polymorphisms (SNPs) in different genes (rs2249492 in COLA1A, rs4434184 in SOX2, rs2162540 in FGFR2, rs11696257 in MAFB, and rs881301 in FGFR1) with Class III malocclusion. Materials and Methods: A total of 10 patients, comprising 5 with Skeletal Class I and 5 with Skeletal Class III malocclusion, were included in the present study. Salivary DNA samples were collected and analyzed using Sanger sequencing. Digital tracing was performed on lateral cephalometric radiographs by using AutoCAD software for digitization to assess the anterio-posterior and vertical relationship of the maxillary and mandibular arch. Results: Out of five genes polymorphisms only two genes polymorphisms (SOX2 and FGFR1) showed an association with Cl.III malocclusion. Conclusion: This study reveals that SOX2 and FGFR1 genetic polymorphisms may be responsible for Class III malocclusion. However, more study with a larger participant pool is required to confirm these findings.
(1) Background: Human papillomavirus (HPV) infection is significantly associated with oropharyngeal squamous cell carcinoma (HPV-OPSCC), which is one of the fastest-growing cancer incidences ...globally. Dental practitioners play a crucial role in the primary and secondary prevention of HPV-OPSCC. There is little known about dental students' awareness regarding HPV-OPSCC and HPV vaccination, as well as their intention to promote 'primordial prevention' among their patients. HPV vaccine, and the extent of their professional responsibilities. (2) Methods: This cross-sectional study was conducted in the western region of Saudi Arabia and involved undergraduate dental students (
= 688) from six public and private dental schools. Participants were requested to complete a sequential-section anonymous online survey, with 257 successfully completing all sections of the questionnaire. The association between participant characteristics and HPV-OPSCC, HPV vaccination awareness ratings, and perceived engagement in prevention were analyzed using ANOVA and chi-squared testing. A binary logistic regression analysis was conducted to examine the variables linked to these outcomes. (3) Results: Generally, the overall level of awareness of HPV-OPSCC and HPV vaccination was acceptable, with an average score of 53.44 ± 29.3 out of 100. However, a significant knowledge gap was observed, with 53% of respondents being unaware of the common sites for HPV-OPSCC and 63.8% being uninformed of the appropriate age for HPV vaccination. Females and those with a prior history of sexually transmitted diseases (STDs) had considerably higher levels of HPV vaccination knowledge (
< 0.05). The participants showed a favorable attitude towards their responsibility of informing patients about HPV-OPSCC and advocating HPV immunization. (4) Conclusions: This study underscores the need to enhance dental students' understanding of HPV-OPSCC and HPV immunization, enabling them to effectively engage in primary and secondary preventative efforts against HPV-OPSCC.
Plant cells release tiny membranous vesicles called extracellular vesicles (EVs), which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. These plant-derived EVs ...(PDEVs) are safe and easily extractable and have been shown to have therapeutic effects against inflammation, cancer, bacteria, and aging. They have shown promise in preventing or treating colitis, cancer, alcoholic liver disease, and even COVID-19. PDEVs can also be used as natural carriers for small-molecule drugs and nucleic acids through various administration routes such as oral, transdermal, or injection. The unique advantages of PDEVs make them highly competitive in clinical applications and preventive healthcare products in the future. This review covers the latest methods for isolating and characterizing PDEVs, their applications in disease prevention and treatment, and their potential as a new drug carrier, with special attention to their commercial viability and toxicological profile, as the future of nanomedicine therapeutics. This review champions the formation of a new task force specializing in PDEVs to address a global need for rigor and standardization in PDEV research.
The personalized regenerative therapeutic strategies applicable in the structural and functional repair of maxillofacial/dental defects are expected to extend beyond the limits of what is currently ...possible in the management of dentofacial anomalies and treating malocclusions. The application of undifferentiated stem cells (SCs), including signaling molecule control and individualized tissue engineering based on targeted therapies, has been proposed to overcome therapeutic limitations and complications associated with treatments for craniofacial defects, including severe orthodontic discrepancies. This scoping, prospective review discusses comprehensively the current knowledge and prospects for improving clinical outcomes by the application of novel cell-required and cell-free regenerative strategies in biomedicine. The existing evidence, although scant, suggests that patients receiving an orthodontic treatment could benefit from precise tissue augmentation, allowing enhancement of tooth movement generated by orthognathic forces; faster, more predictable alignment of dental arches; optimal management of periodontal complications; and prevention of external root resorption. Ultimately, enriching orofacial tissues and "customizing" the repair of congenital/acquired defects in the craniofacial region can be vastly enhanced to provide a positive therapeutic outcome and improve patients' quality of life.
Aims
This qualitative study aimed to assess people with congenital bleeding disorders (CBDs) perspectives on why their dentists refused to treat them.
Methods
Using validated and reliable questions, ...people with CBDs were asked about their attitude toward dental visit and teeth brushing, perceived thought about dentists’ knowledge and skill in treating them, perceived dental anxiety, and perceived barriers toward receiving dental services. Free text responses were added to report reasons of why people with CBDs could not brush their teeth sometimes and why the dentists refused to treat them. An open card sorting method was used to analyze participants free text reports.
Results
A total of 30 participants were recruited for the purpose of this qualitative study (70% adults and 30% children). Hemophilia A affected the majority of both groups. The majority of participants (n = 20, 67%) reported that they have been refused to be treated by their dentists (71% of adults versus 56% of children, as reported by their parents, p‐value = 0.398). Adult participants reported that they have been refused to be treated by dentists due to fear of dentists from uncontrolled gingival bleeding, their dentists’ beliefs that no dental treatment required for them, their thoughts that their dentists will refuse to treat them and difficulty of accommodating the dental visit with other medical appointments. Parents of children reported other reasons such as parents did not ask for dental treatments, difficulty of dental treatment to dentists, young age of patient, and poor accessibility to dental services due to long waiting list. Fear of adult participants from uncontrolled gingival bleeding (n = 4, 57%) and poor compliance of children toward teeth brushing (n = 2, 29%) were the reasons behind why they could not brush their teeth sometimes.
Conclusions
Among several reported reasons, fear of dentists from uncontrolled gingival bleeding was the most reported reason of why dentists refused to treat adults with CBDs. While other reasons were reported by parents of children with CBDs such as parents did not ask for dental treatment to their children, difficulty of dental treatment to dentists, young age of patients, and poor accessibility due to long waiting list.
Background
The spleen is a multi‐functional organ that supports the immune system and is involved in the production of platelets and red blood cells. People with splenic dysfunctions or asplenia are ...predisposed to infection; hence, adults with splenic dysfunction, splenectomy or congenital asplenia may require antibiotic prophylaxis prior to dental procedures to prevent possible bacteraemia which could be caused by dental extraction.
Aims
To assess the current evidence to determine whether adults with splenic dysfunction, splenectomy or congenital asplenia require antibiotic prophylaxis prior to dental extraction.
Materials and Methods
A systematic review following the Preferred Reporting Item for Systematic Review and Meta‐analyses (PRISMA) guidelines (registration number: CRD42021230933) was conducted using Ovid MEDLINE and EMBASE databases. PROSPERO was searched for ongoing or recently completed systematic reviews and The ClinicalTrials.gov was searched for ongoing or recently completed trials. The evidence of all articles was evaluated based on the Oxford Level of Evidence. The Grading of Recommendations Assessment, Development and Evaluation approach was used to summarise the evidence.
Results
Nine articles published from 1984 to 2016 were included in the data synthesis and analysis. The included articles presented level 5 evidence; hence, all were identified at level D of the recommendation.
Conclusions
Antibiotic prophylaxis should not be routinely prescribed for adults with splenic dysfunctions, splenectomy or congenital asplenia prior to dental extraction as sepsis post‐dental extraction in this group of patients is very rare.
High-risk Human Papillomavirus (HPV) infections have recently emerged as an independent risk factor in head and neck squamous cell carcinoma (HNSCC). There has been a marked increase in the incidence ...of HPV-induced HNSCC subtype, which demonstrates different genetics with better treatment outcome. Despite the favourable prognosis of HPV-HNSCC, the treatment modality, consisting of high dose radiotherapy (RT) in combination with chemotherapy (CT), remains similar to HPV-negative tumours, associated with toxic side effects. Epidermal growth factor receptor (EGFR) is overexpressed in over 80% of HNSCC and correlates with RT resistance. EGFR inhibitor Cetuximab is the only FDA approved targeted therapy for both HNSCC subtypes, however the response varies between HNSCC subtypes. In HPV-negative HNSCC, Cetuximab sensitises HNSCC to RT improving survival rates. To reduce adverse cytotoxicity of CT, Cetuximab has been approved for treatment de-escalation of HPV-positive HNSCC. The results of several recent clinical trials have concluded differing outcome to HPV-negative HNSCC. Here we investigated the role of EGFR in HPV-positive HNSCC response to RT. Remarkably, in HPV-positive HNSCC cell lines and in vivo tumour models, EGFR activation was strongly indicative of increased RT response. In response to RT, EGFR activation induced impairment of DNA damage repair and increased RT response. Furthermore, EGFR was found to downregulate HPV oncoproteinE6 expression and induced p53 activity in response to RT. Collectively, our data uncovers a novel role for EGFR in virally induced HNSCC and highlights the importance of using EGFR-targeted therapies in the context of the genetic makeup of cancer.
•EGFR activation is strongly correlated with worse survival outcome and radiotherapy resistance in HNSCC.•HPV-positive HNSCC patients showed inferior outcomes when treated with Cetuximab, the only FDA-approved targeted agent for HNSCC.•EGFR activation in HPV-positive HNSCC cell lines induced clear radiosensitisation in mice.•EGFR overexpression inhibited DNA damage repair , suppressed HPV-E6, restorating p53 activity and increased radiotherapy response.•EGFR function differs in HPV---derived HNSCC subtype, which needs to be considered in using EGFR targeted therapies for treating head and neck cancer patients.
Head and neck squamous cell carcinoma (HNSCC), a group of heterogeneous cancers, represent an aggressive molecular biology and treatment challenge. These cancers develop near critical anatomical ...structures in the head and neck, which are sensitive to treatment, resulting in severe toxicities and reduced quality of life. High-risk Human Papilloma Virus (HPV) infections have recently emerged as an independent risk factor in HNSCC. There has been a marked increase in the incidence of HPV-positive HNSCC subtype. The HPV-induced tumours demonstrate different genetics and have favourable prognosis, however the treatment modality, which is mainly, high dose radiotherapy (RT) in combination with chemotherapy, is similar to HPV-negative tumours and is associated with severe adverse side effects. Epidermal growth factor receptor (EGFR) is overexpressed in more than 80% of HNSCC resulting in increased proliferation, survival, angiogenesis and is known to play an important role in HNSCC therapy resistance. EGFR inhibitor Cetuximab is the only FDA-approved targeted therapy for both HNSCC subtypes, though the response seems to be different between the two molecular subtypes. In HPV-negative tumours, EGFR overexpression is correlated with RT resistance and EGFR inhibitor Cetuximab sensitises HNSCC to radiotherapy and improves survival rates. The precise role of EGFR in HPV-positive HNSCC is unclear, nonetheless for the purpose of reducing adverse cytotoxicity of chemotherapy Cetuximab has been used for treatment de-intensification of HPV-positive HNSCC, but the results of several large-scale clinical trials have concluded surprising and differing outcome to HPV-negative cancers. This study investigated the role of EGFR in HPV-positive HNSCC cell lines particularly its role in radiotherapy response. The study results showed that EGFR signalling pathway is differentially regulated in HPV-derived HNSCC. In contrary to HPV-negative cancers, where EGFR activates DNA repair, in HPV-positive HNSCC cell lines EGFR activation strongly inhibited radiation-induced DNA repair resulting in enhanced radiosensitivity. EGFR was also found to significantly reduce HPV16-E6 expression resulting in restoration of p53 activity and induction of cell death. Notably, EGFR showed a differing regulatory role in modulating tumour-derived exosomes in HNSCC subtypes. The data presented in this study demonstrated an alternative role for EGFR in virally derived HNSCC cells and highlighted the importance of considering using EGFR-targeted therapy in the context of the genetic makeup of the tumour.
إن العلاقة بين مستوى الهيموجلوبين وانتشار تسوس الأسنان معروفة، ولكن المعلومات المتوفرة قليلة عن العلاقة بين مستوى الهيموجلوبين ومقياس التسوس، والأسنان المفقودة والمحشوة في السعودية. تهدف هذه الدراسة ...لتقييم العلاقة بين مستوى الهيموجلوبين لدى عينة عشوائية من الأطفال ومعدل تسوس، وفقد الأسنان وحشوها في السعودية.
تمت هذه الدراسة المقطعية على مدى ١١ شهرا خلال الفترة من مايو ٢٠١٤م وحتى إبريل ٢٠١٥م لعدد ١٦٠ طفلا من الزائرين لمستشفى طب الأسنان بجامعة الملك عبدالعزيز - جدة - السعودية. تم تقسيمهم إلى مجموعتين: المجموعة الأولى بدون فقر الدم والمجموعة الثانية الذين تم تشخيصهم بمرض فقر الدم. وتم قياس نسبة تسوس الأسنان بواسطة استخدام مقياس التسوس، والأسنان المفقودة والمحشوة. وبعد ذلك تم التحليل الإحصائي لتقييم العلاقة بينهما في البحث.
ضمت الدراسة ١٦٠ طفلا، ولوحظ أن الأطفال ذوي مستوى متدني من الهيموجلوبين في الدم (المجموعة الثانية) يعانون من نسبة أعلى في تسوس الأسنان بالمقارنة بالأطفال غير المصابين بفقر الدم (المجموعة الأولى) حسب مقياس التسوس، والأسنان المفقودة والمحشوة.
نتائج هذا البحث تبين أن الأطفال الذين لديهم مستويات متدنية للهيموجلوبين في الدم لديهم احتمالية عالية للإصابة بتسوس الأسنان. بينت نتائج البحث أهمية القيام بحملة صحة عامة تركز على الوعي بصحة الفم والوقاية من فقر الدم وعلاجه.
The relation between haemoglobin levels and the prevalence of dental caries is well-recognized; however, relatively little information is available regarding the decayed, missing and filled teeth (dmft) index in relation to haemoglobin levels in KSA. The objective of this study was to assess the association between the haemoglobin levels and the dmft index in a random sample of paediatric dental patients who visit a teaching hospital in KSA.
This 11-month cross sectional study was conducted at King Abdulaziz University Hospital, Jeddah, KSA from May 2014 to April 2015. A total of 160 children with dental caries were divided into 2 groups: non-anaemic and anaemic groups. The prevalence of caries was measured using the dmft index and was compared between the two groups. Statistical analyses were performed using the chi-square tests at a 0.05% significance level.
One hundred-sixty subjects were recruited in this study. Children with lower mean haemoglobin levels (anaemic children) had significantly higher mean dmft indices (11.20 ± 2.6) than the non-anaemic children (9.66 ± 1.2%, p < 0.05).
This study suggests that children with lower haemoglobin levels may be prone to develop dental caries. This study emphasizes the need for public health campaigns regarding oral hygiene and the prevention and treatment of anaemia.
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