Validation of Selected Head and Neck Cancer Prognostic Markers from the Pathology Atlas in an Oral Tongue Cancer Cohort.
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ABSTRACT:
SUBMITTER: Wirsing AM
PROVIDER: S-EPMC8156750 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS). The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Mesenchymal, Hypoxia and Classical); one OSCC-specific signature (13 genes); two metabolism-related signatures (3 genes and signatures raised from 6 metabolic pathways associated with prognosis in HNSCC and OSCC, respectively); a hypoxia gene signature. The molecular stratification and high versus low expression of the signatures were correlated with OCFS by Kaplan-Meier analyses. The association of gene expression profiles among the tested biological models and clinical covariates was tested through variance partition analysis. Patients with Mesenchymal, Hypoxia and Classical clusters showed an higher risk of malignant transformation in comparison with immune-related ones (log-rank test, p = 0.0052) and they expressed four enriched hallmarks: "TGF beta signaling" "angiogenesis", "unfolded protein response", "apical junction". Overall, 54 cases entered in the immune related clusters, while the remaining 32 cases belonged to the other clusters. No other signatures showed association with OCFS. Our variance partition analysis proved that clinical and molecular features are able to explain only 21% of gene expression data variability, while the remaining 79% refers to residuals independent of known parameters. Applying the existing signatures derived from HNSCC to OPL, we identified only a protective effect for immune-related signatures. Other gene expression profiles derived from overt cancers were not able to identify the risk of malignant transformation, possibly because they are linked to later stages of cancer progression. The availability of a new well-characterized set of OPL patients and further research is needed to improve the identification of adequate prognosticators in OPLs.
| S-EPMC7466020 | biostudies-literature
Project description:BackgroundPoor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs.MethodsIn a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption.ResultsInverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer.ConclusionGood oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.
| S-EPMC4959929 | biostudies-literature
Project description:Therapeutic improvements and epidemiologic changes in head and neck cancer (HNC) over the last three decades have led to increased numbers of survivors, resulting in greater need for continuing management of oral and dental health in this population. Generally, the HNC patient oral health needs are complex, requiring multidisciplinary collaboration among oncologists and dental professionals with special knowledge and training in the field of oral oncology. In this review, we focus on the impact of cancer treatment on oral health, and the oral care protocols recommended prior to, during and after cancer therapy. The management of oral complications such as mucositis, pain, infection, salivary function, taste and dental needs are briefly reviewed. Other complications and their management, including osteonecrosis of the jaw and recurrent/new primary malignancies are also described. This review offers clinical protocols and information for medical providers to assist in understanding oral complications and their management in HNC patients and survivors, and their oral and dental health care needs. Oral and dental care is impacted by the patient's initial oral and dental status, as well as the specific cancer location, type, and its treatment; thus, close communication between the dental professional and the oncology team is required for appropriate therapy.
| S-EPMC6460838 | biostudies-literature
Project description:B7-H3 was the only molecule identified with prognostic potential from a recent systematic review of the prognostic value of immune checkpoints in oral cancer. We aimed to validate this finding in a multicenter international cohort. We retrospectively retrieved 323 oral tongue squamous cell carcinoma (OTSCC) samples from three different countries (Brazil, Finland, and Norway) for immunostaining and scoring for B7-H3. We evaluated tumor immunogenicity by analyzing the amount of tumor-infiltrating lymphocytes and divided the tumors into immune hot and cold. To increase the reliability of the results, both digital and manual visual scoring were used. Survival curves were constructed based on the Kaplan-Meier method, and the Cox proportional hazard model was utilized for univariate and multivariate survival analysis. B7-H3 expression was not significantly associated with overall or disease-specific survival in the whole OTSCC cohort. When divided into immune hot and cold tumors, high B7-H3 expression was significantly associated with poor disease-specific and overall survival in the immune hot group, depending on the scoring method and the country of the cohort. This was achieved only in the univariate analysis. In conclusion, B7-H3 was a negative prognosticator for OTSCC patient survival in the subgroup of immune hot tumors, and was not validated as a prognosticator in the full cohort. Our findings suggest that the immune activity of the tumor should be considered when testing immune checkpoints as biomarkers.
| S-EPMC8134649 | biostudies-literature
Project description:BackgroundIntensity modulated radiotherapy for head and neck cancer necessitates accurate definition of organs at risk (OAR) and clinical target volumes (CTV). This crucial step is time consuming and prone to inter- and intra-observer variations. Automatic segmentation by atlas deformable registration may help to reduce time and variations. We aim to test a new commercial atlas algorithm for automatic segmentation of OAR and CTV in both ideal and clinical conditions.MethodsThe updated Brainlab automatic head and neck atlas segmentation was tested on 20 patients: 10 cN0-stages (ideal population) and 10 unselected N-stages (clinical population). Following manual delineation of OAR and CTV, automatic segmentation of the same set of structures was performed and afterwards manually corrected. Dice Similarity Coefficient (DSC), Average Surface Distance (ASD) and Maximal Surface Distance (MSD) were calculated for "manual to automatic" and "manual to corrected" volumes comparisons.ResultsIn both groups, automatic segmentation saved about 40% of the corresponding manual segmentation time. This effect was more pronounced for OAR than for CTV. The edition of the automatically obtained contours significantly improved DSC, ASD and MSD. Large distortions of normal anatomy or lack of iodine contrast were the limiting factors.ConclusionsThe updated Brainlab atlas-based automatic segmentation tool for head and neck Cancer patients is timesaving but still necessitates review and corrections by an expert.
| S-EPMC3722083 | biostudies-literature
Project description:Deformable image registration (DIR) is often validated based on a distance-to-agreement (DTA) criterion of automatically propagated anatomical landmarks that were manually identified. Due to human observer variability, however, the performance of the registration method is diluted. The purpose of this study was to evaluate an analysis of variance (ANOVA) based validation to account for such observer variation.Weekly cone beam CTs (CBCTs) of ten head and neck cancer patients undergoing five weeks of radiotherapy were used. An expert identified 23 anatomical features (landmarks) on the planning CT. The landmarks were automatically propagated to the CBCT using multiregion-of-interest (mROI) registration. Additionally, two human observers independently localized these landmarks on the CBCTs. Subsequently, ANOVA was used to compute the variance of each observer on the pairwise distance (PWD).ANOVA based analysis demonstrated that a classical DTA approach underestimated the precision for the mROI due to human observer variation by about 25%. The systematic error (accuracy) of mROI ranged from 0.13 to 0.17 mm; the variability (1 SD) (precision) ranged from 1.3 to 1.5 mm demonstrating that its performance is dominated by the precision.The PWD-ANOVA method accounts for human observer variation allowing a better estimation of the of DIR errors.
| S-EPMC3494727 | biostudies-other
Project description:Quality assured pathology services are integral to provision of optimal management for patients with head and neck cancer. Pathology services vary globally and are dependent on resources in terms of both laboratory provision and availability of a highly trained and accredited workforce. Ensuring a high-quality pathology service depends largely on close working and effective communication between the clinical team providing treatment and the pathologists providing laboratory input. Laboratory services should be quality assured by achieving external accreditation, most often by conforming to International Organization for Standardization (ISO) standards such as ISO15189 sometimes with ISO17025 or alternatively ISO17020. Quality of diagnostic reporting can be assured by the ISO but clinical teams should endeavor to work with pathologists who engage in continuing professional development, external quality assurance and audit. Research also contributes to diagnostic reporting quality. A number of initiatives in the UK such as the EPSRC/MRC funded Molecular Pathology Nodes and the National Cancer Research Institute Cellular-Molecular Pathology initiative (C-M Path), for example, have linked pathologists, industry and researchers. This has resulted in centers leading in digital innovation, artificial intelligence, translational research and clinical trials supported by pathologists. For rare tumors and contemporary molecular diagnostics, biopsy material can increasingly be shared with expert specialist pathologists working in specialist centers, particularly by using digital pathology platforms with potentially global reach. High quality services for the majority of diagnostic processes required for head and neck cancer management is best provided by local pathologists where communication with the treating team is more effective than with pathologists working in remote centers. Quality assurance is an increasingly important aspect of pathology, assuring not only effective turnaround times and accuracy for the diagnostic service but also high quality consistent reporting for clinical trials where even small pathology errors can potentially produce a significant bias and in the worst case negate the value of a completed trial. Better outcomes have been associated with centers engaged in clinical trials than in non-participating centers. Provision of a quality assured pathology service should extend to both the research and diagnostic services.
| S-EPMC7105634 | biostudies-literature
Project description:PurposePatients with head and neck cancer (HNC) are at high risk of malnutrition due to eating difficulties partly mediated by sensory alterations and salivary dysfunction. Clinical studies have mostly focused on taste and smell alterations, while changes in oral somatosensory perception are largely understudied. The study aimed to investigate oral somatosensory (tactile, texture, chemesthetic, and thermal) responses and salivary functions of HNC patients in comparison to healthy controls.MethodsA cross-sectional study was conducted using psychophysical tests in HNC patients (n = 30) and in age- and gender-matched control subjects (n = 30). The tests included measurements of point-pressure tactile sensitivity, whole-mouth chemesthetic stimulation, food texture discrimination, and temperature discrimination. Salivary functions, including hydration, saliva consistency, pH, volume, and buffering capacity, were also evaluated.ResultsHNC patients demonstrated significantly lower chemesthetic sensitivity (for medium and high concentrations, p < 0.05), thermal sensitivity (p = 0.038), and salivary functions (p = 0.001). There were indications of lower tactile sensitivity in the patient group (p = 0.101). Patients were also less sensitive to differences in food roughness (p = 0.003) and firmness (p = 0.025).ConclusionThis study provided evidence that sensory alterations in HNC patients extend beyond their taste and smell. The measurements demonstrated lower somatosensory responses, in part associated with their reduced salivary function. Oral somatosensory alterations and salivary dysfunction may consequently impart the eating experience of HNC patients. Thus, further investigations on food adjustments for this patient group seem warranted.
| S-EPMC10570204 | biostudies-literature
Project description:Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03-1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41-3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65-1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.
| S-EPMC6488153 | biostudies-literature
Project description:Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high-throughput data from The Cancer Genome Atlas (TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas (HNSCC) including oropharyngeal squamous cell carcinoma (OPSCC) and other subtypes. In this study, we analyzed miRNA-seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified miRNAs were further tested with an independent cohort. miRNA-seq data from TCGA was also analyzed to identify prognostic miRNAs in oral cavity squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC). Our study identified that miR-193b-3p and miR-455-5p were positively associated with survival, and miR-92a-3p and miR-497-5p were negatively associated with survival in OPSCC. A combined expression signature of these four miRNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four miRNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4-miRNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.
| S-EPMC4944889 | biostudies-literature