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Microbiology Spectrum Jul 2024The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA)...
The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2-9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6-17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity ( = 28/35) for HPV16 and HPV33 and a specificity of 97% ( = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% ( = 17/20), while in samples with <750 µL plasma, it was 73% ( = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material.IMPORTANCEHPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC.
Topics: Humans; DNA, Viral; Papillomavirus Infections; Cell-Free Nucleic Acids; Polymerase Chain Reaction; Oropharyngeal Neoplasms; Papillomaviridae; Female; Sensitivity and Specificity; Male; Middle Aged; Aged; Human papillomavirus 16; Human Papillomavirus Viruses
PubMed: 38829114
DOI: 10.1128/spectrum.00024-24 -
Prognostic role of lymph node micrometastasis in oral and oropharyngeal cancer: A systematic review.Oral Oncology Jul 2024An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph... (Review)
Review
BACKGROUND
An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC.
METHODS
PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact.
RESULTS
Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis.
CONCLUSION
The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.
Topics: Humans; Oropharyngeal Neoplasms; Mouth Neoplasms; Prognosis; Neoplasm Micrometastasis; Lymphatic Metastasis; Lymph Nodes; Carcinoma, Squamous Cell
PubMed: 38823172
DOI: 10.1016/j.oraloncology.2024.106808 -
Scientific Reports May 2024While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also...
While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also leaving room for further investigation into the underlying mechanisms. This study was designed to delve into the possible causal link between periodontitis and 20 standard cancers while concurrently identifying potential mediators. We initiated a Mendelian randomization analysis that drew from either publicly accessible or personally obtained genome-wide association study (GWAS) datasets. The inverse variance weighting (IVW) method served as our primary tool for analysis. To ensure the strength and consistency of our results, we implemented additional strategies, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), bolstered by funnel plots. Our analysis unveiled an elevated risk of head and neck cancer concomitant with periodontitis (p = 0.041, OR 0.999, 95% CI 0.999-1.000), specifically a heightened risk of oropharyngeal cancer (p = 0.022, OR 0.999, 95% CI 0.999-1.000). As a result of probing into potential mediators, Fusobacterium nucleatum emerged as a likely intermediary in the promoting effect of periodontitis on oropharyngeal cancer (p = 0.021, OR 0.999, 95% CI 0.998-1.000). Inversely, basal cell carcinoma and endometrial cancer demonstrated an association with an increased incidence of periodontitis (basal cell carcinoma: p = 0.020, OR 0.987, 95% CI 0.976-0.998; endometrial cancer: p = 0.027, OR 0.984, 95% CI 0.970-0.998). However, periodontitis exerted no significant causal impact on the 19 other common cancers or the three subtypes of head and neck cancer. To conclude, our results support the theory that periodontitis contributes to an enhanced risk of head and neck cancer, particularly oropharyngeal cancer, with Fusobacterium nucleatum functioning as a potential intermediary.
Topics: Humans; Mendelian Randomization Analysis; Periodontitis; Oropharyngeal Neoplasms; Genome-Wide Association Study; Risk Factors; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38822160
DOI: 10.1038/s41598-024-63447-4 -
Journal of Medical Virology Jun 2024Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma...
Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16 immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16 immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.
Topics: Humans; Oropharyngeal Neoplasms; Retrospective Studies; Papillomavirus Infections; Middle Aged; Male; Female; Paraffin Embedding; Oncogene Proteins, Viral; Genotype; Aged; DNA, Viral; Papillomaviridae; Polymerase Chain Reaction; Genotyping Techniques; China; Adult; Formaldehyde; Human Papillomavirus Viruses
PubMed: 38818787
DOI: 10.1002/jmv.29716 -
Internal Medicine (Tokyo, Japan) May 2024Pulmonary tumor embolisms (PTEs) are primarily caused by adenocarcinoma. However, only a few cases of oropharyngeal carcinoma have been reported. We herein report a...
Pulmonary tumor embolisms (PTEs) are primarily caused by adenocarcinoma. However, only a few cases of oropharyngeal carcinoma have been reported. We herein report a 47-year-old man who presented with a fever, cough, and dyspnea 6 months after treatment for stage II oropharyngeal carcinoma. Chest computed tomography revealed centrilobular granular and nodular shadows and subpleural consolidation. A transbronchial lung biopsy revealed a mass of squamous tumor cells forming emboli in the small vessels, resulting in the diagnosis of PTE due to oropharyngeal carcinoma. Therefore, PTE should be considered for patients with a history of hypoxia.
PubMed: 38811224
DOI: 10.2169/internalmedicine.3596-24 -
Community Dental Health May 2024Autoimmune diseases (AIDs) are linked to oropharyngeal cancer (OPC), but the exact nature of this association remains unclear. This study aims to examine the potential...
BACKGROUND
Autoimmune diseases (AIDs) are linked to oropharyngeal cancer (OPC), but the exact nature of this association remains unclear. This study aims to examine the potential causal effect of AIDs on the risk of developing OPC.
METHOD
Information regarding AIDs was collected from the UK Biobank dataset and the Finn Gen study. OPC data were sourced from the IEU Open GWAS project. All data were derived from European populations. Inverse variance weighted (IVW) to two-sample Mendelian randomization (MR) was complemented by weighted median and MR Egger validation analyses.
RESULT
The development of asthma (AS), multiple sclerosis (MS), and rheumatoid arthritis (RA) influenced the risk of developing OPC. However, the reverse MR analysis did not provide evidence for the impact of OPC on AIDs. Sensitivity analysis using MR corroborated the IVW results. The IVW results indicate OR values of 1.004 for AS, 0.936 for MS, and 1.0002 for RA.
CONCLUSION
This MR study supports a causal relationship between asthma and rheumatoid arthritis for OPC in a European population. Multiple sclerosis was protective against OPC.
Topics: Humans; Oropharyngeal Neoplasms; Autoimmune Diseases; Mendelian Randomization Analysis; Multiple Sclerosis; Arthritis, Rheumatoid; Asthma; Genome-Wide Association Study; Risk Factors; Causality; United Kingdom; Male; Female
PubMed: 38809691
DOI: 10.1922/CDH_00274Hua07 -
Asian Pacific Journal of Cancer... May 2024The current research compared radiobiological and dosimetric results for simultaneous integrated boost (SIB) plans employing RapidArc and IMRT planning procedures in...
Assessment of the Dosimetric Index from IMRT and Rapid arc Plan for Oropharyngeal Cancer with Simultaneous Integrated Boost (SIB) Technique in Combination with EUD-based NTCP and TCP Radiobiological Models.
PURPOSE
The current research compared radiobiological and dosimetric results for simultaneous integrated boost (SIB) plans employing RapidArc and IMRT planning procedures in oropharyngeal cancer from head-and-neck cancer (HNC) patients.
MATERIALS AND METHODS
The indigenously developed Python-based software was used in this study for generation and analysis. Twelve patients with forty-eight total plans with SIB were planned using Rapid arc (2 and 3 arcs) and IMRT (7 and 9 fields) and compared with radiobiological models Lyman, Kutcher, Burman (LKB) and EUD (Equivalent Uniform Dose) along with physical index such as homogeneity index(HI), conformity index(CI) of target volumes.
RESULTS
These models' inputs are the dose-volume histograms (DVHs) calculated by the treatment planning system (TPS). The values obtained vary from one model to the other for the same technique and patient. The maximum dose to the brainstem and spinal cord and the mean dose to the parotids were analysed both dosimetrically and radiobiologically, such as the LKB model effective volume, equivalent uniform dose, EUD-based normal tissue complication probability, and normal tissue integral dose. The mean and max dose to target volume with conformity, homogeneity index, tumor control probability compared with treatment times, and monitor units.
CONCLUSION
Rapid arc (3 arcs) resulted in significantly better OAR sparing, dose homogeneity, and conformity. The findings indicate that the rapid arc plan has improved dose distribution in the target volume compared with IMRT, but the tumor control probability obtained for the two planning methods, Rapid arc (3 arcs) and IMRT (7 fields), are similar. The treatment time and monitor units for the Rapid arc (3 arcs) were superior to other planning methods and considered to be standard in head & neck radiotherapy.
Topics: Humans; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Oropharyngeal Neoplasms; Radiotherapy Dosage; Organs at Risk; Prognosis; Radiometry; Radiobiology
PubMed: 38809623
DOI: 10.31557/APJCP.2024.25.5.1515 -
Revista Paulista de Pediatria : Orgao... 2024Pediatric cardiac tumors are rare and, among them, 90% are benign. Cardiac fibroma is the second most frequent tumor, after rhabdomyoma. The objective of this study is...
OBJECTIVE
Pediatric cardiac tumors are rare and, among them, 90% are benign. Cardiac fibroma is the second most frequent tumor, after rhabdomyoma. The objective of this study is to report a case of cardiac fibroma diagnosed incidentally in a patient admitted with acute viral bronchiolitis.
CASE DESCRIPTION
A 5-month-old male infant was admitted to the pediatric emergency department with acute viral bronchiolitis requiring hospitalization. He presented a detectable respiratory syncytial virus in oropharyngeal swab, blood test with lymphocytosis and a chest radiography revealed cardiomegaly. Further cardiologic testing was performed detecting elevation of cardiac biomarkers, an electrocardiogram with alteration of left ventricular repolarization and echocardiogram with a heterogeneous mass in the left ventricular, with areas of calcification. A chest angiotomography suggested rhabdomyosarcoma or cardiac fibroma and a magnetic resonance showed a mass, with characteristics suggesting fibroma. The final diagnosis was made after two cardiac catheterizations for biopsy of the lesion, confirming cardiac fibroma by anatomopathological examination. Because the patient had moderate to severe systolic dysfunction, he was submitted to heart transplant.
COMMENTS
One third of cardiac fibromas are asymptomatic, generally diagnosed late through tests ordered for other reasons. The gold-standard test for definitive diagnosis is biopsy. Cardiac fibroma usually does not present spontaneous regression and, in most cases, partial or total surgical resection is necessary. When tumors are unresectable, heart transplantation should be indicated. It is essential to have detailed characterization of the cardiac mass to establish the most appropriate therapeutic approach for each patient.
Topics: Humans; Male; Heart Neoplasms; Fibroma; Infant; Incidental Findings; Bronchiolitis, Viral; Acute Disease
PubMed: 38808864
DOI: 10.1590/1984-0462/2024/42/2022157 -
Journal of Robotic Surgery May 2024We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year...
We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.
Topics: Humans; Robotic Surgical Procedures; Retrospective Studies; Oropharyngeal Neoplasms; Male; Female; Middle Aged; Aged; Treatment Outcome; Neoplasm Recurrence, Local; Australia; Adult; Papillomavirus Infections; Carcinoma, Squamous Cell; Margins of Excision; Squamous Cell Carcinoma of Head and Neck; Neck Dissection; Aged, 80 and over
PubMed: 38806847
DOI: 10.1007/s11701-024-01910-0 -
Frontiers in Oral Health 2024HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of...
INTRODUCTION
HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood.
OBJECTIVE
To investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV- OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk.
MATERIALS AND METHODS
A retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication.
RESULTS
HPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV-positive group (Log-Rank = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV- OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs.
CONCLUSION
This investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.
PubMed: 38803348
DOI: 10.3389/froh.2024.1390081