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Medicina (Kaunas, Lithuania) Oct 2022: The research aimed at evaluating the capacity of salivary exosomal miR-10b-5p and miR-486-5p for oral and oropharyngeal cancer detection. : The saliva samples were...
: The research aimed at evaluating the capacity of salivary exosomal miR-10b-5p and miR-486-5p for oral and oropharyngeal cancer detection. : The saliva samples were harvested from histopathological diagnosed oral and oropharyngeal squamous cell carcinoma patients and healthy volunteer subjects. The exosomes were isolated by differential ultracentrifugation and quantified by Nano Track Analysis. The microRNAs were extracted and quantified from salivary exosomes by quantitative Real-Time Polymerase Chain Reaction. : This research comprised fifty participants. When compared to healthy controls, salivary exosomal miR-486-5p was elevated and miR-10b-5p was reduced in oral and oropharyngeal squamous cell carcinoma. Moreover, miR-486-5p had a high expression level in stage II of cancer in comparison to the other cancer stages. The cancer samples presented an increased exosome dimension compared to the control samples. : Salivary exosomal miR-10b-5p and miR-486-5p have an altered expression in oral and oropharyngeal cancer.
Topics: Humans; Exosomes; Gene Expression Regulation, Neoplastic; MicroRNAs; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 36295638
DOI: 10.3390/medicina58101478 -
Journal of Experimental & Clinical... Sep 2022Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and...
The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors.
BACKGROUND
Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and second-line settings. However, only 15-20% of patients benefit from this treatment, a feature increasingly ascribed to the peculiar characteristics of the tumor immune microenvironment (TIME).
METHODS
Immune-related gene expression profiling (GEP) and multiplex immunofluorescence (mIF) including spatial proximity analysis, were used to characterize the TIME of 39 treatment-naïve oropharyngeal squamous cell carcinomas (OPSCC) and the corresponding lymph node metastases. GEP and mIF results were correlated with disease-free survival (DFS). HPV-positive tumors disclosed a stronger activation of several immune signalling pathways, as well as a higher expression of genes related to total tumor-infiltrating lymphocytes, CD8 T cells, cytotoxic cells and exhausted CD8 cells, than HPV-negative patients. Accordingly, mIF revealed that HPV-positive lesions were heavily infiltrated as compared to HPV-negative counterparts, with a higher density of T cells and checkpoint molecules. CD8+ T cells appeared in closer proximity to tumor cells, CD163+ macrophages and FoxP3+ cells in HPV-positive primary tumors, and related metastases. In HPV-positive lesions, PD-L1 expression was increased as compared to HPV-negative samples, and PD-L1+ tumor cells and macrophages were closer to PD-1+ cytotoxic T lymphocytes. Considering the whole cohort, a positive correlation was observed between DFS and higher levels of activating immune signatures and T cell responses, higher density of PD-1+ T cells and their closer proximity to tumor cells or PD-L1+ macrophages. HPV-positive patients with higher infiltration of T cells and macrophages had a longer DFS, while CD163+ macrophages had a negative role in prognosis of HPV-negative patients.
CONCLUSIONS
Our results suggest that checkpoint expression may reflect an ongoing antitumor immune response. Thus, these observations provide the rationale for the incorporation of ICI in the loco-regional therapy strategies for patients with heavily infiltrated treatment-naïve OPSCC, and for the combination of ICI with tumor-specific T cell response inducers or TAM modulators for the "cold" OPSCC counterparts.
Topics: B7-H1 Antigen; Carcinoma, Squamous Cell; Forkhead Transcription Factors; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Oropharyngeal Neoplasms; Papillomavirus Infections; Programmed Cell Death 1 Receptor; Spatial Analysis; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 36123711
DOI: 10.1186/s13046-022-02481-4 -
Frontiers in Public Health 2023Higher educational attainment (EA) has proven to be beneficial for preventing and treating various types of cancers. Currently, there is little evidence on the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Higher educational attainment (EA) has proven to be beneficial for preventing and treating various types of cancers. Currently, there is little evidence on the association between EA and prevention of oral cavity and pharyngeal cancer (OCPC).
METHODS
Several databases were searched until October 1, 2022, and a meta-analysis was performed. A Mendelian randomization (MR) study was conducted with EA (i.e., the exposure) data derived from the Social Science Genetic Association Consortium and 6,034 cases of OCPC (i.e., outcome) selected from the Integrative Epidemiology Unit genome-wide association study. Five methods were used to evaluate the causality between EA and OCPC. The leave-one-out sensitivity test, MR-Egger regression, and multivariable MR (MVMR) analysis were applied to evaluate the MR results.
RESULTS
The meta-analysis included 36 eligible studies. EA was significantly and negatively associated with OCPC risk (odds ratio [OR]: 0.439, 95% confidence interval [CI]: 0.383-0.503, < 0.001). MR analysis revealed that the risk of OCPC, oropharyngeal cancer, and oral cavity cancer decreased with an increase in education (OR: 0.349, 95% CI: 0.222-0.548, < 0.001; OR: 0.343, 95% CI: 0.198-0.597; < 0.001; OR: 0.342, 95% CI: 0.195-0.601, < 0.001, respectively). Even after correcting for mediators, high EA still significantly reduced the risk of OCPC (OR: 0.361, 95% CI: 0.281-0.463, < 0.001).
CONCLUSION
Both the meta-analysis and MR results demonstrated that high levels of EA can reduce the risk of OCPC in the general population.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Oropharyngeal Neoplasms; Educational Status; Databases, Factual
PubMed: 37124787
DOI: 10.3389/fpubh.2023.1132035 -
Head & Neck Jul 2021Outcomes of oropharyngeal squamous cell carcinoma (OPSCC) after development of distant metastases (DM) in the context of human papillomavirus (HPV) tumor status remain...
BACKGROUND
Outcomes of oropharyngeal squamous cell carcinoma (OPSCC) after development of distant metastases (DM) in the context of human papillomavirus (HPV) tumor status remain controversial in the literature.
METHODS
OPSCC patients with DM treated between June 2015 and March 2019 were included from a prospectively enrolled database. Characteristics of DM including sites, episodes, and timing of disease were analyzed in addition to survival after DM.
RESULTS
Sixty-nine HPV-positive and 18 HPV-negative OPSCC patients with DM were included. The 2-year survival after DM was higher for HPV-positive patients (54.0% vs. 11.3%, p < 0.001). HPV-positive patients did not demonstrate greater episodes or sites of DM. Multiple sites of DM, early development of DM, and Charlson comorbidity Index were independently associated with worse survival after DM.
CONCLUSIONS
While multiple sites, early DM, and comorbidities were poor prognostic factors, OPSCC patients with distant progression can have substantial survival after DM, including M1 patients.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck
PubMed: 33738875
DOI: 10.1002/hed.26678 -
Journal (Canadian Dental Association) Dec 2022The aims of this study were to determine demographic profiles, tumour characteristics and treatment factors related to oral cavity and oropharyngeal cancer (OCC and OPC)...
OBJECTIVES
The aims of this study were to determine demographic profiles, tumour characteristics and treatment factors related to oral cavity and oropharyngeal cancer (OCC and OPC) and comparatively analyze these cancers in the adult population of Alberta, Canada, over 12 years.
METHODS
Demographic, tumour characteristics and treatment data regarding OCC and OPC incidence in Alberta residents ≥18 years in 2005-2017 were extracted from the Alberta Cancer Registry database. Age-standardized incidence and mortality rates (ASIR and ASMR) were computed.
RESULTS
Among 3448 OCC and OPC cases, mean (standard deviation) age at diagnosis was 63.9 (14.4) and 60.1 (10.2) years, respectively. There was a male predilection for both OCC (58.2%) and OPC (81.7%). With some fluctuations, ASIR remained the same for OCC but increased for OPC. ASMR increased for both. The most common site for OCC was tongue and for OPC tonsil. Squamous cell carcinoma was the most common diagnosis for OCC and OPC. Involvement of at least 1 lymph node was observed in 38.5% of OCC and 85.8% of OPC cases. For 45.2% of OCC and 82.3% of OPC cases, diagnosis occurred at stage IV. The most common initial treatments for OCC were surgery, alone or combined with radiation, whereas radiation with chemotherapy was the main treatment modality for OPC.
CONCLUSION
The incidence of OPC in younger males was higher than that of OCC. Although incidence of OPC per 100 000 population increased over the 12-year study period, it remained largely unchanged for OCC. For both cancers, initial diagnoses were made at advanced stages, with almost twice as many stage IV OPC cases than OCC cases.
Topics: Adult; Male; Humans; Mouth Neoplasms; Alberta; Oropharyngeal Neoplasms; Incidence
PubMed: 37098276
DOI: No ID Found -
The Lancet. Digital Health Jun 2023Pretreatment identification of pathological extranodal extension (ENE) would guide therapy de-escalation strategies for in human papillomavirus (HPV)-associated... (Randomized Controlled Trial)
Randomized Controlled Trial
Screening for extranodal extension in HPV-associated oropharyngeal carcinoma: evaluation of a CT-based deep learning algorithm in patient data from a multicentre, randomised de-escalation trial.
BACKGROUND
Pretreatment identification of pathological extranodal extension (ENE) would guide therapy de-escalation strategies for in human papillomavirus (HPV)-associated oropharyngeal carcinoma but is diagnostically challenging. ECOG-ACRIN Cancer Research Group E3311 was a multicentre trial wherein patients with HPV-associated oropharyngeal carcinoma were treated surgically and assigned to a pathological risk-based adjuvant strategy of observation, radiation, or concurrent chemoradiation. Despite protocol exclusion of patients with overt radiographic ENE, more than 30% had pathological ENE and required postoperative chemoradiation. We aimed to evaluate a CT-based deep learning algorithm for prediction of ENE in E3311, a diagnostically challenging cohort wherein algorithm use would be impactful in guiding decision-making.
METHODS
For this retrospective evaluation of deep learning algorithm performance, we obtained pretreatment CTs and corresponding surgical pathology reports from the multicentre, randomised de-escalation trial E3311. All enrolled patients on E3311 required pretreatment and diagnostic head and neck imaging; patients with radiographically overt ENE were excluded per study protocol. The lymph node with largest short-axis diameter and up to two additional nodes were segmented on each scan and annotated for ENE per pathology reports. Deep learning algorithm performance for ENE prediction was compared with four board-certified head and neck radiologists. The primary endpoint was the area under the curve (AUC) of the receiver operating characteristic.
FINDINGS
From 178 collected scans, 313 nodes were annotated: 71 (23%) with ENE in general, 39 (13%) with ENE larger than 1 mm ENE. The deep learning algorithm AUC for ENE classification was 0·86 (95% CI 0·82-0·90), outperforming all readers (p<0·0001 for each). Among radiologists, there was high variability in specificity (43-86%) and sensitivity (45-96%) with poor inter-reader agreement (κ 0·32). Matching the algorithm specificity to that of the reader with highest AUC (R2, false positive rate 22%) yielded improved sensitivity to 75% (+ 13%). Setting the algorithm false positive rate to 30% yielded 90% sensitivity. The algorithm showed improved performance compared with radiologists for ENE larger than 1 mm (p<0·0001) and in nodes with short-axis diameter 1 cm or larger.
INTERPRETATION
The deep learning algorithm outperformed experts in predicting pathological ENE on a challenging cohort of patients with HPV-associated oropharyngeal carcinoma from a randomised clinical trial. Deep learning algorithms should be evaluated prospectively as a treatment selection tool.
FUNDING
ECOG-ACRIN Cancer Research Group and the National Cancer Institute of the US National Institutes of Health.
Topics: Humans; Human Papillomavirus Viruses; Retrospective Studies; Papillomavirus Infections; Deep Learning; Extranodal Extension; Oropharyngeal Neoplasms; Algorithms; Carcinoma; Tomography, X-Ray Computed
PubMed: 37087370
DOI: 10.1016/S2589-7500(23)00046-8 -
Current Oncology (Toronto, Ont.) May 2022The prevalence of oropharyngeal squamous cell carcinoma has been increasing in North America due to human papillomavirus-associated disease. It is molecularly distinct... (Review)
Review
The prevalence of oropharyngeal squamous cell carcinoma has been increasing in North America due to human papillomavirus-associated disease. It is molecularly distinct and differs from other head and neck cancers due to the young population and high survival rate. The treatment regimens currently in place cause significant long-term toxicities. Studies have transitioned from mortality-based outcomes to patient-reported outcomes assessing quality of life. There are many completed and ongoing trials investigating alternative therapy regimens or de-escalation strategies to minimize the negative secondary effects while maintaining overall survival and disease-free survival. The goal of this review is to discuss the most recent advancements within the field while summarizing and reviewing the available evidence.
Topics: Alphapapillomavirus; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Quality of Life; Squamous Cell Carcinoma of Head and Neck
PubMed: 35621685
DOI: 10.3390/curroncol29050295 -
Radiotherapy and Oncology : Journal of... Jan 2020The aim was to evaluate in oropharyngeal carcinoma the: (1) incidence and predictors of retropharyngeal (RP) lymph node (LN) involvement, (2) pattern of...
INTRODUCTION
The aim was to evaluate in oropharyngeal carcinoma the: (1) incidence and predictors of retropharyngeal (RP) lymph node (LN) involvement, (2) pattern of ipsilateral/bilateral/contralateral-only RP LNs (3) location of RP LNs in relation to contouring guidelines.
METHODS
Single centre retrospective analysis of 402 patients with oropharyngeal carcinoma treated non-surgically between 2010 and 2017. All patients had a baseline FDG PET-CT and contrast-enhanced MRI and/or CT. All cases with reported abnormal RP LNs underwent radiology review.
RESULTS
Abnormal RP LNs were identified in 40/402 (10%) of patients. On multivariate analysis, RP LN involvement was associated with posterior pharyngeal wall/soft palate primaries (OR 10.13 (95% CI 2.29-19.08), p = 0.002) and contralateral cervical LN involvement (OR 2.26 (95% CI 1.05-4.86), p = 0.036). T stage, largest LN size, levels of ipsilateral LN level involvement, HPV and smoking status did not predict risk. 5/402 (1.2%) patients had bilateral RP involvement. 3/402 patients (0.7%) had contralateral-only RP LNs. All patients with contralateral RP LNs had contralateral neck nodes or primary cancers extending across midline. In 5/40 (12.5%) cases with involved RP LNs, the RP LNs were superior to hard palate/upper edge of body of C1 vertebra.
CONCLUSIONS
RP LNs were identified in 10% of oropharyngeal carcinoma patients, and were associated with contralateral neck disease and/or posterior pharyngeal wall/soft palate primary. Contralateral RP LN involvement was rare and associated with contralateral neck disease and/or primary crossing midline, suggesting potential for omission from target volumes for selected patients. Involvement of RP LNs close to the skull base highlights the need for generous elective outlining.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Incidence; Lymph Nodes; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Oropharyngeal Neoplasms; Positron Emission Tomography Computed Tomography; Retrospective Studies; Young Adult
PubMed: 31431388
DOI: 10.1016/j.radonc.2019.07.021 -
Oral Oncology Dec 2021Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in... (Review)
Review
Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com).
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Retrospective Studies
PubMed: 34798575
DOI: 10.1016/j.oraloncology.2021.105620 -
Viruses Jul 2021Squamous cell carcinoma of unknown primary (SCCUP) is a challenging diagnostic subgroup of oropharyngeal squamous cell carcinoma (OPSCC). The incidence of SCCUP is... (Review)
Review
Squamous cell carcinoma of unknown primary (SCCUP) is a challenging diagnostic subgroup of oropharyngeal squamous cell carcinoma (OPSCC). The incidence of SCCUP is increasing in parallel with the well-documented increase in OPSCC and is likewise driven by the increase in human papillomavirus (HPV). The SCCUP patient often presents with a cystic lymph node metastasis and undergoes an aggressive diagnostic and treatment program. Detection of HPV in cytologic specimens indicates an oropharyngeal primary tumor origin and can guide the further diagnostic strategy. Advances in diagnostic modalities, e.g., transoral robotic surgery and transoral laser microsurgery, have increased the successful identification of the primary tumor site in HPV-induced SCCUP, and this harbors a potential for de-escalation treatment and increased survival. This review provides an overview of HPV-induced SCCUP, diagnostic modalities, and treatment options.
Topics: Alphapapillomavirus; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Oropharyngeal Neoplasms; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 34372502
DOI: 10.3390/v13071297