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Scientific Reports Jan 2020Pathological staging and histological grading systems are useful, but imperfect, predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Aberrant...
Pathological staging and histological grading systems are useful, but imperfect, predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Aberrant promoter methylation is the main type of epigenetic modification that plays a role in the inactivation of tumor suppressor genes. To identify new potential prognostic markers, we investigated the promoter methylation status of five neuropeptide receptor genes. The methylation status of the target genes was compared with clinical characteristics in 278 cases; 72 hypopharyngeal cancers, 54 laryngeal cancers, 75 oropharyngeal cancers, and 77 oral cavity cancers were studied. We found that the NTSR1, NTSR2, GHSR, MLNR, and NMUR1 promoters were methylated in 47.8%, 46.8%, 54.3%, 39.2%, and 43.5% of the samples, respectively. GHSR and NMUR1 promoter methylation independently predicted recurrence in HNSCC. In patients with oropharyngeal cancer (n = 75), GHSR and NMUR1 promoter methylation significantly correlates with survival in surgically treated patients. We classified our patients as having a low, intermediate, or high-risk of death based on three factors: HPV status, and GHSR and NMUR1 promoter methylation. The disease-free survival (DFS) rates were 87.1%, 42.7%, and 17.0%, respectively. Combined data analysis of the methylation status of ten-eleven translocation (TET) family genes indicated a trend toward greater methylation indices as the number of TET methylation events increased. In the current study, we presented the relationship between the methylation status of the GHSR and NMUR1 genes and recurrence in HNSCC, specifically in risk classification of oropharyngeal carcinomas cases with HPV status.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; DNA Methylation; DNA-Binding Proteins; Dioxygenases; Disease-Free Survival; Female; Humans; Male; Middle Aged; Mixed Function Oxygenases; Neoplasm Recurrence, Local; Neoplasm Staging; Oropharyngeal Neoplasms; Promoter Regions, Genetic; Proto-Oncogene Proteins; Receptors, Ghrelin; Receptors, Neurotransmitter; Squamous Cell Carcinoma of Head and Neck
PubMed: 31974445
DOI: 10.1038/s41598-020-57920-z -
Journal of Otolaryngology - Head & Neck... Apr 2020The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Patients with HPV-associated and HPV-unassociated...
BACKGROUND
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Patients with HPV-associated and HPV-unassociated OPSCC differ in many aspects, which may also impact their diagnostic and management timelines. This study aims at studying the patient, primary health care (PHC) and specialist-care (SC) delays and possible differences between these two patient groups in seeking medical care.
METHODS
We reviewed all new patients with OPSCC treated between 2016 and 2018 at our institute, which covers a referral area of 1.6 million people. We collected data on patients' symptoms and factors influencing why they sought medical care using a patient-reported questionnaire and hospital records. We compared delays based on patient and tumor characteristics.
RESULTS
In our study population of 83 patients, the median patient delay was 30 days (range, 0-366), with a median PHC delay of 15 days (range, 0 days-2.5 years), and a median SC delay of 54 days (range, 12-231). The SC delay was further divided into diagnostic hospital delay and treatment delay, each with a median length of 16 days (range, 0-237) and 29 days (range, 0-73), respectively. Furthermore, we found that p16 status did not associate with delays. A longer patient delay associated with specific tumor factors, such as a larger primary tumor and a lower UICC 7th edition stage. Patients that had multiple visits or did not have a follow-up visit scheduled at the initial appointment had longer PHC delays. Treatment delay was significantly longer for patients scheduled for (chemo-)radiotherapy than for those undergoing surgery with or without (chemo-)radiotherapy.
CONCLUSIONS
Although delays remained short for the majority of OPSCC patients, long delays require further evaluation and improvement of management. Awareness of presenting symptoms among cancer risk patients and prompt referral practice or a follow-up visit at PHC represent key factors to shortening these delays. Ultimately, the causes for delays in SC appear multifactorial and require institutional quality control.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Finland; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasm Grading; Oropharyngeal Neoplasms; Papillomavirus Infections; Referral and Consultation; Smoking; Time-to-Treatment
PubMed: 32326977
DOI: 10.1186/s40463-020-00413-w -
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 -
Medicine May 2019This study used radiomics image analysis to examine the differences of texture feature values extracted from oropharyngeal and hypopharyngeal cancer positron emission... (Observational Study)
Observational Study
This study used radiomics image analysis to examine the differences of texture feature values extracted from oropharyngeal and hypopharyngeal cancer positron emission tomography (PET) images on various tumor segmentations, and finds the proper and stable feature groups. A total of 80 oropharyngeal and hypopharyngeal cancer cases were retrospectively recruited. Radiomics method was applied to the PET image for the 80 oropharyngeal and hypopharyngeal cancer cases to extract texture features from various defined metabolic volumes. Kruskal-Wallis one-way analysis of variance method was used to test whether feature value difference exists between groups, which were grouped by stage, response to treatment, and recurrence. If there was a significant difference, the corresponding feature cutoff value was applied to the Kaplan-Meier estimator to estimate the survival functions. For the various defined metabolic volumes, there were 16 features that had significant differences between early (T1, T2) and late tumor stages (T3, T4). Five images and 2 textural features were found to be able to predict the tumor response and recurrence, respectively, with the areas under the receiver operating characteristic curves reaching 0.7. The histogram entropy was found to be a good predictor of overall survival (OS) and primary relapse-free survival (PRFS) of oropharyngeal and hypopharyngeal cancer patients. Textural features from PET images provide predictive and prognostic information in tumor staging, tumor response, recurrence, and have the potential to be a prognosticator for OS and PRFS in oropharyngeal and hypopharyngeal cancer.
Topics: Adult; Aged; Female; Humans; Hypopharyngeal Neoplasms; Image Processing, Computer-Assisted; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Oropharyngeal Neoplasms; Positron Emission Tomography Computed Tomography; Prognosis; ROC Curve; Retrospective Studies
PubMed: 31045814
DOI: 10.1097/MD.0000000000015446 -
International Journal of Clinical and... 2014In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal... (Comparative Study)
Comparative Study
In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal lamina, connective tissue degradation and surrounding stroma markers. We evaluated these associations in Chilean patients. A convenience sample of 37 cases of OCSCC (n=16) and OPSCC (n=21) was analyzed clinically (TNM, clinical stage) and histologically (WHO grade of differentiation, pattern of tumor invasion). We assessed the expression of p53, Ki67, HOXA1, HOXB7, type IV collagen (ColIV) and carcinoma-associated fibroblast (α-SMA-positive cells). Additionally we conducted a univariate/bivariate analysis to assess the relationship of these variables with survival rates. Males were mostly affected (56.2% OCSCC, 76.2% OPSCC). Patients were mainly diagnosed at III/IV clinical stages (68.8% OCSCC, 90.5% OPSCC) with a predominantly infiltrative pattern invasion (62.9% OCSCC, 57.1% OPSCC). Significant association between regional lymph nodes (N) and clinical stage with OCSCC-HOXB7 expression (Chi-Square test P < 0.05) was observed. In OPSCC a statistically significant association exists between p53, Ki67 with gender (Chi-Square test P < 0.05). In OCSCC and OPSCC was statistically significant association between ki67 with HOXA1, HOXB7, and between these last two antigens (Pearson's Correlation test P < 0.05). Furthermore OPSCC-p53 showed significant correlation when it was compared with α-SMA (Kendall's Tau-c test P < 0.05). Only OCSCC-pattern invasion and OPSCC-primary tumor (T) pattern resulted associated with survival at the end of the follow up period (Chi-Square Likelihood Ratio, P < 0.05). Clinical, histological and immunohistochemical features are similar to seen in other countries. Cancer proliferation markers were associated strongly from each other. Our sample highlights prognostic value of T and pattern of invasion, but the conclusions may be limited and should be considered with caution (small sample). Many cases were diagnosed in the advanced stages of the disease, which suggests that the diagnosis of OCSCC and OPSCC is made late.
Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Chi-Square Distribution; Chile; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Likelihood Functions; Male; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Oropharyngeal Neoplasms; Predictive Value of Tests; Retrospective Studies; Risk Factors; Squamous Cell Carcinoma of Head and Neck; Time Factors
PubMed: 25337241
DOI: No ID Found -
Auris, Nasus, Larynx Oct 2016The purpose of this study was to suggest general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to... (Review)
Review
The purpose of this study was to suggest general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0-14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations, such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not related to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation.
Topics: Carcinoma, Adenoid Cystic; Disease Management; Humans; Lymph Nodes; Lymphatic Metastasis; Mouth Neoplasms; Neck; Neck Dissection; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Radiotherapy
PubMed: 27017314
DOI: 10.1016/j.anl.2016.02.013 -
Journal of Otolaryngology - Head & Neck... Jan 2017Epigenetic modifications are heritable changes in gene expression that do not directly alter DNA sequence. These modifications include DNA methylation, histone... (Review)
Review
Epigenetic modifications are heritable changes in gene expression that do not directly alter DNA sequence. These modifications include DNA methylation, histone post-translational modifications, small and non-coding RNAs. Alterations in epigenetic profiles cause deregulation of fundamental gene expression pathways associated with carcinogenesis. The role of epigenetics in oropharyngeal squamous cell carcinoma (OPSCC) has recently been recognized, with implications for novel biomarkers, molecular diagnostics and chemotherapeutics. In this review, important epigenetic pathways in human papillomavirus (HPV) positive and negative OPSCC are summarized, as well as the potential clinical utility of this knowledge.This material has never been published and is not currently under evaluation in any other peer-reviewed publication.
Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Epigenomics; Humans; Oropharyngeal Neoplasms
PubMed: 28143553
DOI: 10.1186/s40463-017-0185-3 -
Head & Neck Sep 2016There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations.... (Review)
Review
BACKGROUND
There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)-associated oropharyngeal SCC.
METHODS
The Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use.
RESULTS
A multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high-risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC.
CONCLUSION
T1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1-2N1-2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1-2N2b-3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1299-1309, 2016.
Topics: Aged; Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Delphi Technique; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neck Dissection; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Oropharyngeal Neoplasms; Oropharynx; Papillomavirus Infections; Pharyngectomy; Practice Guidelines as Topic; Prognosis; Risk Assessment; Societies, Medical; Squamous Cell Carcinoma of Head and Neck; Survival Analysis
PubMed: 27330003
DOI: 10.1002/hed.24447 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Oct 2022In recent years, the incidence of oropharyngeal carcinoma (OPC) is increasing, while the better prognosis of patients with Human papillomavirus (HPV) positive...
In recent years, the incidence of oropharyngeal carcinoma (OPC) is increasing, while the better prognosis of patients with Human papillomavirus (HPV) positive oropharyngeal carcinoma has been confirmed in a number of studies. There are a variety of detection methods for HPV-associated oropharyngeal carcinoma. Including P16 immunohistochemistry, Polymerase Chain Reaction (PCR) or In situ hybridization (ISH) detection of HPV DNA, HPV RNA, Revers transcriptase Polymerase Chain Reaction (RT PCR) was used to detect HPV RNA. The better prognosis of patients with HPV-positive oropharyngeal carcinoma has led to the emergence of a large number of degraded treatment trials. The traditional P16 test has certain limitations in the diagnosis of patients with HPV-positive oropharyngeal carcinoma. It is necessary to combine with other detection methods to accurately screen out patients with HPV-positive oropharyngeal carcinoma and better apply to degraded therapy. In this article, we will briefly introduce the trend of HPV-associated oropharyngeal carcinoma, the detection methods and the new progress of degraded treatment trials.
Topics: Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; RNA
PubMed: 36217663
DOI: 10.13201/j.issn.2096-7993.2022.10.015 -
European Journal of Cancer (Oxford,... Apr 2017In the context of locally advanced oropharyngeal cancer (LAOC) treated with definitive radiotherapy (RT) (combined with chemotherapy or cetuximab), the aims of this...
PURPOSE
In the context of locally advanced oropharyngeal cancer (LAOC) treated with definitive radiotherapy (RT) (combined with chemotherapy or cetuximab), the aims of this study were: (1) to identify PET-FDG parameters correlated with overall survival (OS) from a first cohort of patients; then (2) to compute a prognostic score; and (3) finally to validate this scoring system in a second independent cohort of patients.
MATERIALS AND METHODS
A total of 76 consecutive patients (training cohort from Rennes) treated with chemoradiotherapy or RT with cetuximab for LAOC were used to build a predictive model of locoregional control (LRC) and OS based on PET-FDG parameters. After internal calibration and validation of this model, a nomogram and a scoring system were developed and tested in a validation cohort of 46 consecutive patients treated with definitive RT for LAOC in Lausanne.
RESULTS
In multivariate analysis, the metabolic tumour volume (MTV) of the primary tumour and the lymph nodes were independent predictive factors for LRC and OS. Internal calibration showed a very good adjustment between the predicted OS and the observed OS at 24 months. Using the predictive score, two risk groups were identified (median OS 42 versus 14 months, p < 0.001) and confirmed in the validation cohort from Lausanne (median OS not reached versus 26 months, p=0.008).
CONCLUSIONS
This is the first report of a PET-based nomogram in oropharyngeal cancer. Interestingly, it appeared stronger than the classical prognostic factors and was validated in independent cohorts markedly diverging in many aspects, which suggest that the observed signal was robust.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cetuximab; Chemoradiotherapy; Cisplatin; Female; Humans; Male; Middle Aged; Neoplasm Staging; Nomograms; Oropharyngeal Neoplasms; Positron Emission Tomography Computed Tomography; Prognosis; Radiotherapy, Intensity-Modulated; Young Adult
PubMed: 28237868
DOI: 10.1016/j.ejca.2017.01.018