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Cancer Treatment and Research... 2021Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET-CT) is clinically useful and extensively used... (Observational Study)
Observational Study
INTRODUCTION
Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET-CT) is clinically useful and extensively used in initial staging and follow-up of patients with head and neck squamous cell carcinoma (HNSCC). We studied the potential prognostic significance of primary tumor maximum standard uptake value (SUVmax) by 18F-FDG PET-CT in oropharyngeal cancer.
METHODS
Sixty patients with early and locally advanced histopathologically proven oropharyngeal squamous cell cancer were staged using FDG PET-CT at diagnosis. All patient received radiation therapy and concurrent chemotherapy (in stage III and IVA disease) and were assessed prospectively for treatment outcome. Groups were created based on stage and cut off for SUVmax. The association of SUVmax of primary tumour and stage with disease-free survival and overall survival was analyzed by univariate and multivariate statistics.
RESULTS
In univariate analysis, a primary tumour SUVmax of greater than 13.0 and advanced stage (IVA) predicted inferior disease-free survival (P=0.0241 and 0.0005, respectively) and overall survival (P=0.0510, toward significance and 0.0003, respectively). In proportional hazards analysis, stage was significant only when adjusted for primary SUVmax.
CONCLUSION
SUVmax failed to demonstrate predictive significance in oropharyngeal cancer, and an increase in primary tumor uptake is possibly a direct effect of advanced disease and consequently increased metabolic activity and aggressiveness.
Topics: Adult; Aged; Chemoradiotherapy; Disease-Free Survival; Feasibility Studies; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Radiopharmaceuticals; Risk Assessment; Squamous Cell Carcinoma of Head and Neck; Tissue Distribution
PubMed: 33461080
DOI: 10.1016/j.ctarc.2021.100305 -
Head & Neck Nov 2020Self-management regimens for oral and oropharyngeal cancer survivors can be complex and challenging. Effective self-management skills can foster better outcomes. We...
BACKGROUND
Self-management regimens for oral and oropharyngeal cancer survivors can be complex and challenging. Effective self-management skills can foster better outcomes. We report on the development, feasibility, and pilot testing of a web-based self-management tool called "Empowered Survivor" (ES) for survivors of oral and oropharyngeal cancer.
METHODS
ES content was developed in two phases, with modules focusing on oral care, swallowing and muscle strength, and long-term follow-up. This single-arm pilot study consisted of a pre-, 2-month, and a 6-month postintervention survey.
RESULTS
Enrollment rates were relatively low. Once enrolled, data collected from the ES website indicated that 81.8% viewed ES. Participants provided positive evaluations of ES. Preliminary results indicate that ES had a beneficial impact on self-management self-efficacy, preparedness for survivorship care, and quality of life. ES improved survivors' engagement in oral self-exams and head and neck strengthening exercises, improved ability to address barriers, and decreased information and support needs.
CONCLUSIONS
This study provides preliminary evidence of engagement, acceptability, and beneficial impact of ES, which should be evaluated in a larger controlled clinical trial.
Topics: Humans; Oropharyngeal Neoplasms; Pilot Projects; Quality of Life; Self-Management; Survivors; Telemedicine
PubMed: 32830404
DOI: 10.1002/hed.26403 -
BMC Cancer Jan 2021Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway,...
BACKGROUND
Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).
METHODS
The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC.
RESULTS
The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression.
CONCLUSIONS
These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC.
Topics: Apoptosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Cycle; Cell Movement; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; Japan; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Rapamycin-Insensitive Companion of mTOR Protein; Regulatory-Associated Protein of mTOR; Survival Rate; Tumor Cells, Cultured
PubMed: 33482765
DOI: 10.1186/s12885-021-07794-9 -
AIDS Research and Human Retroviruses Oct 2019HIV-positive people are at increased risk for malignancies associated with human papillomavirus (HPV) infection, including oropharyngeal squamous cell carcinoma (OPSCC).... (Comparative Study)
Comparative Study
HIV-positive people are at increased risk for malignancies associated with human papillomavirus (HPV) infection, including oropharyngeal squamous cell carcinoma (OPSCC). The purpose of this study was to determine whether cancer treatment disparities exist between HIV-positive and HIV-negative people with OPSCC. We conducted a retrospective cohort study comparing OPSCC treatment adequacy and treatment outcomes in HIV-positive and HIV-negative people in the post-antiretroviral therapy era. Treatment adequacy was determined by measuring two primary endpoints associated with OPSCC survival: time to therapy and total radiation dose. Treatment outcomes were assessed by measuring disease-free and overall survival. We identified a total of 37 HIV-positive and 149 HIV-negative people with OPSCC. HIV-positive people experienced a median delay of 10 days from time of OPSCC diagnosis to start of therapy compared with HIV-negative people [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.38-0.98]. Total post-radiation dose in HIV-positive people was lower than that in HIV-negative people [58.5 Gray (Gy) versus 64.4 Gy, = .04]. HIV-positive people also experienced greater hazards for disease recurrence (HR 3.43, 95% CI 1.39-8.46) and death (HR 4.21, 95% CI 1.29-13.80) compared with HIV-negative people. In conclusion, we detected a clinically important delay in time to therapy as well as worse disease-free and overall survival in HIV-positive people with OPSCC compared with their HIV-negative counterparts. These findings are relevant to understanding how HIV-positive people are diagnosed and undergo therapy for HPV-associated malignancies and highlight the need to address cancer treatment disparities in this group.
Topics: Adult; Aged; Anti-HIV Agents; Carcinoma, Squamous Cell; Combined Modality Therapy; Comorbidity; Confounding Factors, Epidemiologic; Disease-Free Survival; Female; HIV Infections; HIV Seronegativity; HIV Seropositivity; Human papillomavirus 16; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Odds Ratio; Oropharyngeal Neoplasms; Papillomavirus Infections; Proportional Hazards Models; Retrospective Studies; Time-to-Treatment; Tobacco Smoking; Treatment Outcome; United States; Viral Load
PubMed: 31347379
DOI: 10.1089/AID.2019.0009 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Sep 2023To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. A retrospective analysis was performed on 468 pathologically...
To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%(42/66) were synchronous and 36.4%(24/66) were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%(=0.001); The second primary cancer accounted for 11.2%(12/107) of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%(9/12). There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer(8.1%). Among them, 65.0%(13/20) were synchronous and 35.0%(7/20) were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%(2/52) of all deaths in p16 positvie group. The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Topics: Humans; Carcinoma; Oropharyngeal Neoplasms; Retrospective Studies; Neoplasms, Second Primary
PubMed: 37640995
DOI: 10.13201/j.issn.2096-7993.2023.09.007 -
Head & Neck Dec 2022Pretreatment determination of extranodal extension (ENE) has significant clinical implications in human papillomavirus positive (HPV+) oropharyngeal squamous cell... (Meta-Analysis)
Meta-Analysis Review
Pretreatment determination of extranodal extension (ENE) has significant clinical implications in human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Unfortunately there is no gold-standard imaging modality for radiological assessment of ENE in HPV+ OPSCC, leading to subjective assessments and complex decision making concerning ENE. A systematic review of diagnostic test accuracy was therefore undertaken, with five databases systemically searched to evaluate the diagnostic performance of an imaging modality for detection of ENE in HPV+ OPSCC. A meta-analysis was conducted on four CT studies using a random-effects model. While a narrative synthesis was provided for the studies using PET/CT and "CT and MRI." Out of 1772 hits, six studies were included in the review. Meta-analysis on four CT studies showed CT had an overall sensitivity of 77% and specificity of 60%. PET/CT had a sensitivity of 37.5% and specificity of 97%. "CT and MRI" had a sensitivity of 62% and specificity of 78%. Further diagnostic studies involving CT, PET/CT and MRI are ultimately required.
Topics: Humans; Extranodal Extension; Papillomavirus Infections; Positron Emission Tomography Computed Tomography; Carcinoma, Squamous Cell; Neoplasm Staging; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
PubMed: 36071683
DOI: 10.1002/hed.27183 -
Head and Neck Pathology Dec 2021While P16 immunohistochemistry (IHC) is a well-established surrogate marker of Human Papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC), Retinoblastoma...
While P16 immunohistochemistry (IHC) is a well-established surrogate marker of Human Papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC), Retinoblastoma 1 (RB1) loss may lead to p16 overexpression in the absence of HPV. We determined the proportion of p16-positive/HPV-negative OSCC with RB1 loss and other alterations in RB1/p16 pathway, and tested RB1 IHC as a prognostic biomarker for OSCC, along with the 8th edition of AJCC staging manual. P16 and RB1 IHC and HPV DNA in situ hybridization (ISH) were performed on 257 OSCC. High risk HPV RNA ISH, RB1 fluorescence in situ hybridization (FISH), and next generation sequencing (NGS) were done on p16-positive/HPV DNA ISH-negative OSCC. Disease free survival (DFS) was used as an endpoint. In the entire cohort and in p16-positive (n = 184) and p16-negative (n = 73) subgroups, AJCC 8th edition staging correlated with DFS (p < 0.01). RB1 IHC showed RB1 loss in p16-positive OSCC only (79/184, 43%). RB1 loss by IHC is associated with a better DFS, without providing additional prognostic information for patients with p16-positive OSCC. HPV RNA ISH was positive in 12 of 14 HPV DNA ISH-negative cases. RB1 IHC showed loss in 10 of 15 HPV DNA ISH-negative cases and in 1 of 2 HPV RNA ISH-negative cases. Overall, only one case of p16-positive/HPV RNA ISH-negative OSCC showed RB1 loss by IHC (1/184, 0.5%). Of the 10 p16-positive and HPV DNA ISH-negative cases with RB1 loss by IHC, 2 had RB1 hemizygous deletion and 3 showed Chromosome 13 monosomy by FISH. No RB1 mutations were detected by NGS. Other molecular alterations in p16-positive/HPV DNA ISH-negative cases included TP53 and TERT mutations and DDX3X loss. HPV-independent RB1 inactivation rarely results in false positive p16 IHC. RB1 inactivation by high risk HPV E7 oncoprotein may co-exist with RB1 deletion. RB1 loss is a favorable prognosticator and occurs exclusively in p16-positive OSCC. The 8th edition of the AJCC staging manual satisfactorily predicts DFS of OSCC patients.
Topics: Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Disease-Free Survival; E2F1 Transcription Factor; Female; Genome, Viral; High-Throughput Nucleotide Sequencing; Humans; In Situ Hybridization, Fluorescence; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomaviridae; RNA, Viral
PubMed: 33830464
DOI: 10.1007/s12105-021-01317-5 -
Head and Neck Pathology Dec 2021Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human...
Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.
Topics: Carcinoma, Squamous Cell; Genome, Viral; Genotype; High-Throughput Nucleotide Sequencing; Human papillomavirus 16; Humans; Oropharyngeal Neoplasms; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 33797697
DOI: 10.1007/s12105-021-01318-4 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Sep 2023The number of new cases of oropharyngeal cancer is increasing year by year among the world, and HPV infection is one of the risk factors for this malignant tumor.... (Review)
Review
The number of new cases of oropharyngeal cancer is increasing year by year among the world, and HPV infection is one of the risk factors for this malignant tumor. Compared with HPV-negative oropharyngeal cancer, HPV-positive patients are more sensitive to radiotherapy and have a better prognosis, but there is no accepted treatment for HPV-positive patients. Reducing treatment intensity moderately and exploring the best option to minimize side effects of treatment are urgent issues to be addressed. This article reviews the research progress on the treatment improvement of HPV-associated oropharyngeal cancer in recent years.
Topics: Humans; Papillomavirus Infections; Oropharyngeal Neoplasms; Risk Factors
PubMed: 37640997
DOI: 10.13201/j.issn.2096-7993.2023.09.010 -
The British Journal of Radiology Sep 2022The clinical behaviour and outcomes of patients with oropharyngeal cancer (OPC) may be dichotomised according to their association with human papilloma virus (HPV)... (Review)
Review
The clinical behaviour and outcomes of patients with oropharyngeal cancer (OPC) may be dichotomised according to their association with human papilloma virus (HPV) infection. Patients with HPV-associated disease (HPV+OPC) have a distinct demographic profile, clinical phenotype and demonstrate considerably better responses to chemoradiotherapy. This has led to a reappraisal of staging and treatment strategies for HPV+OPC, which are underpinned by radiological data. Structural modalities, such as CT and MRI can provide accurate staging information. These can be combined with ultrasound-guided tissue sampling and functional techniques (such as diffusion-weighted MRI and F-fludeoxyglucose positron emission tomography-CT) to monitor response to treatment, derive prognostic information, and to identify individuals who might benefit from intensification or deintensification strategies. Furthermore, advanced MRI techniques, such as intravoxel incoherent motion and perfusion MRI as well as application of artificial intelligence and radiomic techniques, have shown promise in treatment response monitoring and prognostication. The following review will consider the contemporary role and knowledge on imaging in HPV+OPC.
Topics: Alphapapillomavirus; Artificial Intelligence; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tomography, X-Ray Computed
PubMed: 35687667
DOI: 10.1259/bjr.20220149