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Oncology Reports Aug 2022The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant...
The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer‑specific biomarkers. The application of three membrane‑bound receptors, namely urokinase‑type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)‑positive and 48 HPV‑negative groups, the IHC‑determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow‑up data, overall survival (OS) and recurrence‑free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log‑rank test following Kaplan‑Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor‑specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92‑4.37). Taken together, these results suggest that uPAR, TF and EGFR may be suitable targets for molecular imaging and therapy in OPSCC. In particular, uPAR may be an attractive target owing to their high positive expression rates in tumors and a highly tumor‑specific expression pattern.
Topics: Biomarkers, Tumor; ErbB Receptors; Humans; Molecular Imaging; Molecular Targeted Therapy; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Receptors, Urokinase Plasminogen Activator; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Thromboplastin
PubMed: 35775375
DOI: 10.3892/or.2022.8359 -
Cancer Imaging : the Official... Nov 2005Imaging studies have an important role in defining the extent of oropharyngeal neoplasms and coming to an accurate staging of these lesions. Besides influencing...
Imaging studies have an important role in defining the extent of oropharyngeal neoplasms and coming to an accurate staging of these lesions. Besides influencing treatment choice, imaging studies can also be used to monitor tumour response to treatment, and as an adjunct to clinical follow-up in order to detect treatment failure as early as possible.
Topics: Carcinoma, Squamous Cell; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Neoplasm Staging; Oropharyngeal Neoplasms; Tomography, X-Ray Computed
PubMed: 16361137
DOI: 10.1102/1470-7330.2005.0030 -
ORL; Journal For Oto-rhino-laryngology... 2023The aim of this study was to investigate the impact of primary transoral robotic surgery (TORS) versus radiotherapy (RT) on progression-free survival (PFS), overall...
INTRODUCTION
The aim of this study was to investigate the impact of primary transoral robotic surgery (TORS) versus radiotherapy (RT) on progression-free survival (PFS), overall survival (OS), and 1-year swallowing function for patients with early-stage HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).
METHODS
Patients with stage I-II (AJCC 8th Ed.) HPV-associated OPSCC treated with TORS followed by risk-adapted adjuvant therapy or (chemo)radiotherapy between 2014 and 2019 were identified. PFS, OS, and swallowing outcomes including gastrostomy tube (GT) use/dependence, and Functional Oral Intake Scale (FOIS) change over 1 year were compared.
RESULTS
One hundred sixty-seven patients were analyzed: 116 treated with TORS with or without adjuvant RT and 51 treated with RT (50 chemoRT). The RT group had more advanced tumor/nodal stage, higher comorbidity, and higher rates of concurrent chemotherapy. There were no differences in 3-year PFS (88% TORS vs. 75% RT) or OS (90% vs. 81%) between groups, which persisted after adjusting for stage, age, and comorbidity. GT use/dependence rates were higher in the RT group. Mean (SD) FOIS scores in the TORS group were 6.9 (0.4) at baseline and 6.4 (1.0) at 1 year, compared with 6.7 (0.6) and 5.6 (1.7) for the RT group. Only clinical nodal stage was found to be significantly associated with FOIS change from baseline to 1 year.
CONCLUSION
There were no differences in PFS or OS between patients treated with primary TORS or RT for early-stage HPV-associated OPSCC. Clinical N2 status is associated with FOIS change at 1 year and may be the major factor affecting long-term swallowing function, irrespective of primary treatment modality.
Topics: Humans; Deglutition; Head and Neck Neoplasms; Human Papillomavirus Viruses; Oropharyngeal Neoplasms; Papillomavirus Infections; Robotic Surgical Procedures; Squamous Cell Carcinoma of Head and Neck; Postoperative Complications
PubMed: 37647863
DOI: 10.1159/000531995 -
Cancer Apr 2017
Topics: Carcinoma, Squamous Cell; Female; Humans; Male; Mouth; Oropharyngeal Neoplasms; Papillomaviridae; Sexual Behavior
PubMed: 28195637
DOI: 10.1002/cncr.30563 -
Papillomavirus Research (Amsterdam,... Jun 2018We investigated the prognostic value of pre-treatment hematological parameters in patients with p16-positive oropharyngeal squamous-cell carcinoma (OPSCC).
OBJECTIVES
We investigated the prognostic value of pre-treatment hematological parameters in patients with p16-positive oropharyngeal squamous-cell carcinoma (OPSCC).
MATERIAL AND METHODS
Neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and hemoglobin concentration measurement (Hb), were collected on day one of treatment. Endpoints were overall survival (OS) and progression-free survival (PFS). All patients were planned to receive concurrent chemoradiation. Staging were reviewed according to the recent AJCC 8th edition.
RESULTS
We included 167 patients in this study. In multivariate analyses, a smoking history > 30 packyears was associated with decreased OS (p = 0.009; HR, 3.4827) and PFS (p = 0.042; HR, 2.421); Hb < 12g/dL was associated with impaired OS (p = 0.007; HR, 6.527) and PFS (p = 0.014; HR, 4.092); an NLR > 5 before treatment was associated with decreased OS (p = 0.042; HR, 2.945). Hemoglobin concentration and the NLR were not correlated (p = 0.577), nor anemia and an NLR > 5 (p = 0.167). Patients with an NLR > 5 had a significantly higher rate of disease recurrence (30.8% vs. 8.4%, p = 0.0299, RR = 3.922, 95% CI 1.351-11.386).
DISCUSSION
We found hemoglobin level and the NLR to be independent prognostic factors in p16-positive OPSCC patients. This approach is to be considered for further clinical investigations, and its significance in treatment decision-making should be further explored.
Topics: Adult; Aged; Anemia; Chemoradiotherapy; Clinical Decision-Making; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Hemoglobins; Humans; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Oropharyngeal Neoplasms; Papillomaviridae; Prognosis; Progression-Free Survival; Retrospective Studies; Smoking; Squamous Cell Carcinoma of Head and Neck
PubMed: 29253748
DOI: 10.1016/j.pvr.2017.12.002 -
Wiener Klinische Wochenschrift Nov 2021The aim was to assess the prognostic value of the newly proposed prognostic index (PI) in patients with p16-positive oropharyngeal squamous cell carcinoma.
BACKGROUND
The aim was to assess the prognostic value of the newly proposed prognostic index (PI) in patients with p16-positive oropharyngeal squamous cell carcinoma.
METHODS
Patients treated with primary surgery from 2012 to 2019 with available preoperative (0-2 days) values of C‑reactive protein and white blood cell counts needed for calculation of the PI, were included. Main outcome measures were overall survival (OS) and disease-free survival (DFS). The PI was dichotomized into low (PI = 0) and high (PI ≥ 1).
RESULTS
In this study 36 patients were included. Average overall (OS) and disease-free survival (DFS) were 3.3 years (range 0.2-12.3 years) and 2.8 years (0.0-9.8 years), respectively. The overall mortality was 16.7% (n = 6) and a recurrent disease was observed in 30.6% of patients (n = 11). Low PI was associated with better overall survival (mean OS 10.1 ± 1.4 years, 95% confidence interval, CI 7.3-12.9 years vs. 1.9 ± 0.4, 95% CI 1.3-2.6 years, p < 0.01; mean DFS 8.5 ± 0.7 years, 95% CI 7.1-9.6 years vs. 1.0 ± 0.3 years, 95% CI 0.5-1.5 years, p < 0.01).
CONCLUSION
The PI might be an easily obtainable outcome prognosticator in p16-positive oropharyngeal squamous cell carcinoma patients. Analyzing routinely obtained blood samples can contribute to identifying high-risk patients.
Topics: Disease-Free Survival; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 34143263
DOI: 10.1007/s00508-021-01885-0 -
Oncology (Williston Park, N.Y.) Jul 2023Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC), which accounts for an increasing proportion of all head and neck cancers, represents a... (Review)
Review
Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC), which accounts for an increasing proportion of all head and neck cancers, represents a specific entity with distinct clinical and molecular characteristics. It is now firmly established that patients with HPV-positive oropharyngeal SCC have a significantly improved prognosis because this variant has exquisite radiosensitivity compared with HPV-negative oropharyngeal SCC; thus, it can be targeted with de-escalated approaches using reduced doses of radiation and/or chemotherapy. The overriding goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain high rates of cure and preserve the quality of life for appropriately selected patients with this disease. However, these studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. How treatment paradigms will evolve, particularly in the era of precision medicine, is a provocative question and is the subject of this review.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Prospective Studies; Quality of Life; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Papillomaviridae
PubMed: 37499250
DOI: 10.46883/2023.25921000 -
Oral Oncology Jun 2023Routine haematoxylin and eosin (H&E) photomicrographs from human papillomavirus-associated oropharyngeal squamous cell carcinomas (HPV + OpSCC) contain a wealth of...
Multifactorial estimation of clinical outcome in HPV-associated oropharyngeal squamous cell carcinoma via automated image analysis of routine diagnostic H&E slides and neural network modelling.
OBJECTIVE
Routine haematoxylin and eosin (H&E) photomicrographs from human papillomavirus-associated oropharyngeal squamous cell carcinomas (HPV + OpSCC) contain a wealth of prognostic information. In this study, we developed a high content image analysis (HCIA) workflow to quantify features of H&E images from HPV + OpSCC patients to identify prognostic features and predict patient outcomes.
METHODS
First, we have developed an open-source HCIA tool for single-cell segmentation and classification of H&E images. Subsequently, we have used our HCIA tool to analyse a set of 889 images from diagnostic H&E slides in a retrospective cohort of HPV + OpSCC patients with favourable (FO, n = 60) or unfavourable (UO, n = 30) outcomes. We have identified and measured 31 prognostic features which were quantified in each sample and used to train a neural network (NN) model to predict patient outcomes.
RESULTS
Univariate and multivariate statistical analyses revealed significant differences between FO and UO patients in 31 and 17 variables, respectively (P < 0.05). At the single-image level, the NN model had an overall accuracy of 72.5% and 71.2% in recognising FO and UO patients when applied to test or validation sets, respectively. When considering 10 images per patient, the accuracy of the NN model increased to 86.7% in the test set.
CONCLUSION
Our open-source H&E analysis workflow and predictive models confirm previously reported prognostic features and identifies novel factors which predict HPV + OpSCC outcomes with promising accuracy. Our work supports the use of machine learning in digital pathology to exploit clinically relevant features in routine diagnostic pathology without additional biomarkers.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Eosine Yellowish-(YS); Retrospective Studies; Carcinoma, Squamous Cell; Papillomavirus Infections; Prognosis; Human Papillomavirus Viruses; Head and Neck Neoplasms; Neural Networks, Computer; Papillomaviridae
PubMed: 37098302
DOI: 10.1016/j.oraloncology.2023.106399 -
Journal of Cancer Research and... 2015In recent years there has been change in trends in the incidence of head and neck squamous cell carcinoma (HNSCC) with oropharyngeal carcinoma (OPC) showing an increased... (Review)
Review
In recent years there has been change in trends in the incidence of head and neck squamous cell carcinoma (HNSCC) with oropharyngeal carcinoma (OPC) showing an increased incidence, attributable specifically to infection by human papillomavirus (HPV). At the same time there is change in demographic characteristics and prognosis of this subset of HNSCC. Considering the better prognosis, researchers are trying to reduce the acute and long-term toxicities by alteration of various components of treatment protocols. Although treatment deintensification is an option for this group of patients, there is no standard protocol available and should be tried only in the protocol setting.
Topics: Head and Neck Neoplasms; Humans; Incidence; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 25879328
DOI: 10.4103/0973-1482.151445 -
International Journal of Molecular... Nov 2022Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is... (Review)
Review
Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.
Topics: Humans; Alphapapillomavirus; Papillomaviridae; Oropharyngeal Neoplasms; Biomarkers; Carcinoma
PubMed: 36430813
DOI: 10.3390/ijms232214336