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HNO Apr 2021Etiologically, oropharyngeal squamous cell carcinoma (OPSCC) can be divided into OPSCC caused by noxious agents and human papillomavirus (HPV)-driven carcinoma. These... (Review)
Review
BACKGROUND
Etiologically, oropharyngeal squamous cell carcinoma (OPSCC) can be divided into OPSCC caused by noxious agents and human papillomavirus (HPV)-driven carcinoma. These types differ with regard to clinical features and prognosis-differences which are rooted in the underlying molecular biology of the tumor.
OBJECTIVE
The aim of this work is to provide an overview of the molecular biological characteristics of the genetics, epigenetics, and immunology of OPSCC.
MATERIALS AND METHODS
A literature review was performed on a selection of genetic, epigenetic, and immunological factors characterizing OPSCC.
RESULTS
The understanding of genetic aberrations and their consequences for cancerogenesis and tumor biology is increasing. Epigenetic phenomena are complementing functional relationships. However, epigenetic mechanisms of gene regulation are complex and much research is still required in this field. Immunological aspects of cancer molecular biology have moved into the focus in light of recent advances in the field of immunotherapy.
CONCLUSION
The tumor biology of OPSCC is primarily defined by its HPV status. Additionally, HPV-independent genetic, epigenetic, and immunological signatures are being defined. From these advances, rationales for new treatment concepts may evolve.
Topics: Biology; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis
PubMed: 33215226
DOI: 10.1007/s00106-020-00964-4 -
Seminars in Cutaneous Medicine and... Dec 2015HPV is the most common sexually transmitted disease, but the overwhelming majority of individuals clear the infection. A small percentage of individuals develop... (Review)
Review
HPV is the most common sexually transmitted disease, but the overwhelming majority of individuals clear the infection. A small percentage of individuals develop persistence of oncogenic HPV types, especially HPV-16; and as a result, squamous cell carcinoma can develop in the tonsils and base of the tongue. Over 70% of oropharyngeal cancers are now thought to be associated with oncogenic HPV infection. Immunohistochemistry for p16 protein is often used as a surrogate marker for oncogenic HPV in the oropharyngeal tissues, although alternative HPV DNA testing methods are under intensive study. The clinical profile of patients with HPV-associated oropharyngeal cancer (OPC) differs quite notably from that of traditional head and neck cancer patients, and the prognosis for HPV-associated OPC is significantly better. As a result, experimental clinical trials are focused on de-intensification of therapies with the hope of preserving an improved long-term quality of life for these patients.
Topics: DNA, Viral; Diagnosis, Differential; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Prognosis
PubMed: 26650695
DOI: 10.12788/j.sder.2015.0182 -
Clinical Oral Investigations Dec 2023To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC).
MATERIALS AND METHODS
Literature was searched through October 2022 in main databases to address the question "What is the global prevalence of Human Papillomavirus in oral and oropharyngeal cancer?" Studies had to identify HPV by PCR, ISH, or p16 immunohistochemistry to be eligible. Quality was assessed using the JBI checklist for prevalence studies. Meta-analyses were performed, and reporting followed PRISMA guidelines.
RESULTS
Sixty-five studies were included, and most of them had methodological limitations related to sampling and the HPV detection tool. The pooled prevalence of HPV-positivity was 10% (event rate = 0.1; 95% CI: 0.07, 0.13; P < 0.01; I = 88%) in the oral cavity and 42% (event rate = 0.42; 95% CI: 0.36, 0.49; P = 0.02; I2 = 97%) in oropharynx. The highest HPV prevalence in OSCC was reached by Japan, meanwhile, in OPSCC, Finland and Sweden were the most prevalent. HPV16 is the genotype most frequent with 69% in OSCC and 89% in OPSCC, being the tonsils the intraoral location more affected by HPV (63%, p < 0.01, I 76%).
CONCLUSION
The evidence points to an apparent burden in HPV-related OPSCC, mostly in North America, Northern Europe, and Oceania, especially due to the HPV16 infection suggesting different trends across continents.
CLINICAL RELEVANCE
This updated systematic review and meta-analysis provide sufficient evidence about the global HPV prevalence in OSCC and OPSCC and the most frequent HPV subtype worldwide.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Human Papillomavirus Viruses; Papillomavirus Infections; Prevalence; Mouth Neoplasms; Oropharyngeal Neoplasms; Head and Neck Neoplasms
PubMed: 38158517
DOI: 10.1007/s00784-023-05425-0 -
Cancer May 2021Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct...
BACKGROUND
Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct pathologic nodal systems. Given that quantitative lymph node (LN) burden is the dominant prognostic factor in most head and neck cancers, we investigated whether HPV- and HPV+ OPC warrant divergent pathologic nodal classification.
METHODS
Multivariable Cox regression models of OPC surgical patients identified via U.S. cancer registry data were constructed to determine associations between survival and nodal characteristics. Nonlinear associations between metastatic LN number and survival were modeled with restricted cubic splines. Recursive partitioning analysis (RPA) was used to derive unbiased nodal schema.
RESULTS
Mortality risk escalated continuously with each successive positive LN in both OPC subtypes, with analogous slope. Survival hazard increased by 18.5% (hazard ratio [HR], 1.19 [95% CI, 1.16-1.21]; P < .001) and 19.1% (HR, 1.19 [95% CI, 1.17-1.21]; P < .001), with each added positive LN for HPV- and HPV+ OPC, respectively, up to identical change points of 5 positive LNs. Extranodal extension (ENE) was an independent predictor of HPV- OPC (HR, 1.55 [95% CI, 1.20-1.99]; P < .001) and HPV+ OPC (HR 1.73 [95% CI, 1.36-2.20]; P < .001) mortality. In RPA for both diseases, metastatic LN was the principal nodal covariate driving survival, with ENE as a secondary determinant. Given the similarities across analyses, we propose a concise, unifying HPV-/HPV+ OPC pathologic nodal classification schema: N1, 1-5 LN+/ENE-; N2, 1-5 LN+/ENE+; N3, >5 LN+.
CONCLUSION
HPV- and HPV+ OPC exhibit parallel relationships between nodal characteristics and relative mortality. In both diseases, metastatic LN number represents the principal nodal covariate governing survival, with ENE being an influential secondary element. A consolidated OPC pathologic nodal staging system that is based on these covariates may best convey prognosis.
LAY SUMMARY
The current nodal staging system for oropharyngeal carcinoma (OPC) has divided human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) OPC into distinct systems that rely upon criteria that establish them as separate entities, a complexity that may undermine the core objective of staging schema to clearly communicate prognosis. Our large-scale analysis revealed that HPV- and HPV+ pathologic nodal staging systems in fact mirror each other. Multiple analyses produced conspicuously similar nodal staging systems, with metastatic lymph node number and extranodal extension delineating the highest risk groups that shape prognosis. We propose unifying HPV- and HPV+ nodal systems to best streamline prognostication and maximize staging accuracy.
Topics: Carcinoma; Humans; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis
PubMed: 33595897
DOI: 10.1002/cncr.33414 -
Journal of Global Oncology Sep 2018Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence in the United States and in many countries worldwide primarily as a result of increasing rates... (Review)
Review
Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence in the United States and in many countries worldwide primarily as a result of increasing rates of human papillomavirus (HPV) infection. HPV-positive OPSCC represents a distinct disease entity from head and neck squamous cell carcinoma caused by traditional risk factors such as tobacco and alcohol, with different epidemiology, patterns of failure, and expected outcomes. Because patients with HPV-positive OPSCC have a younger median age and superior prognosis compared with their HPV-negative counterparts, they live longer with the morbidity of treatment, which can be severe. Therefore, efforts are under way to de-escalate therapy in favorable-risk patients while maintaining treatment efficacy. Additional work is being undertaken to discover new therapies that may benefit both HPV-positive and HPV-negative patient subsets. Herein, we will review the available data for the evolving treatment paradigms in OPSCC as well as discuss ongoing clinical trials.
Topics: Carcinoma, Squamous Cell; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Oropharyngeal Neoplasms; Treatment Outcome
PubMed: 30241193
DOI: 10.1200/JGO.2016.006304 -
Folia Medica Cracoviensia Oct 2023Our umbrella review aimed to summarize and revisit the evidence from all of the meta-analyses and systematic reviews regarding the treatments of oropharyngeal squamous... (Review)
Review
INTRODUCTION
Our umbrella review aimed to summarize and revisit the evidence from all of the meta-analyses and systematic reviews regarding the treatments of oropharyngeal squamous cell carcinoma (OPSCC).
MATERIALS AND METHODS
Major medical databases such as PubMed, Scopus, Embase, Web of Science, Google Scholar, Cochrane Library, BIOSIS, and EBSCO were searched. The overall search process was conducted in 3 stages.
RESULTS
Finally, a total of 28 studies met the inclusion criteria and were included in this study. Out of those 28 meta-analyses, a total of 315 primary studies were screened in order to extract the data and perform the statistical analysis. In total, data from 22,619 patients was analyzed.
CONCLUSION
The main objective of the present umbrella review was to summarize and analyze all of the evidence-based data provided by numerous meta-analyses and systematic reviews regarding the treatment of OPSCC. Our study delivers the most up-to-date and evidence-based results regarding the different therapeutic modalities of this malignancy in one concise review, making it the ultimate tool for physicians treating OPSCC.
Topics: Humans; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38310532
DOI: 10.24425/fmc.2023.147217 -
Laryngo- Rhino- Otologie Oct 2021Oropharynx carcinoma (OPSCC) is a genetically heterogeneous tumor group with high prognostic diversity due to its worldwide increase in incidence and the association... (Review)
Review
BACKGROUND
Oropharynx carcinoma (OPSCC) is a genetically heterogeneous tumor group with high prognostic diversity due to its worldwide increase in incidence and the association with the human papillomavirus HPV 16, but also chronic tobacco/alcohol consumption.
OBJECTIVE
The review attempts to present the current view on therapy and prevention of OPSCC with respect to association with HPV 16.
MATERIAL & METHODS
The overview is based on the current relevant literature as well as current studies.
RESULTS & DISCUSSION
The OPSCC presents itself as a very complex, genetically heterogeneous group of head and neck tumors, which should therefore be considered in detail. The currently contradictory trial situation of retrospective studies versus prospective trials, the current TNM classification (8th edition) and the scarce prospective data arguing for non-inferiority of therapy de-intensification attempts currently admonish to encourage a more conservative treatment.
Topics: Carcinoma; Human papillomavirus 16; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Prospective Studies; Retrospective Studies
PubMed: 34614529
DOI: 10.1055/a-1523-9045 -
Cancer Treatment Reviews Jan 2016The incidence of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), which is both biologically and clinically distinct from tobacco- and alcohol-related OPSCC,... (Review)
Review
The incidence of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), which is both biologically and clinically distinct from tobacco- and alcohol-related OPSCC, is dramatically increasing. The finding that individuals with HPV-positive local/regionally advanced OPSCC have a significantly better prognosis than their negative counterparts have led to efforts to de-escalate treatment in those patients to avoid serious side effects and to improve their long-term quality of life, while maintaining treatment efficacy. Identifying diagnostic tests that are able to distinguish cancers etiologically associated with HPV is thus becoming a pressing challenge for researchers. The purpose of this review is to provide an overview of the diagnostic tools presently available to evaluate HPV status in patients with OPSCC and, in particular, to discuss their strengths and weaknesses in identifying those infections that are the real driving force in the oropharyngeal carcinogenesis process.
Topics: Alcohol Drinking; Antibodies, Viral; Biomarkers; Carcinoma, Squamous Cell; Cell Transformation, Viral; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; DNA, Neoplasm; DNA, Viral; Diagnosis, Differential; Humans; Immunohistochemistry; In Situ Hybridization; Neoplasm Proteins; Oncogene Proteins, Viral; Oncogenes; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus E7 Proteins; Papillomavirus Infections; Polymerase Chain Reaction; Repressor Proteins; Retinoblastoma Protein; Smoking; Tumor Suppressor Protein p53
PubMed: 26547133
DOI: 10.1016/j.ctrv.2015.10.009 -
Current Oncology Reports Jul 2020The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic... (Review)
Review
PURPOSE OF REVIEW
The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic factor, and HPV+ OPSCC is considered a distinct pathological entity with dedicated NCCN guidelines and may deserve a more personalized therapeutic strategy. The possibility to reduce surgical invasiveness and acute and late toxicity of radiotherapy/chemotherapy has led to the new concept of de-escalation treatment strategies. In particular, several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. The aim of the present review is to systematically illustrate the current status of research in de-intensification surgical and non-surgical strategies in the treatment of the OPSCC.
RECENT FINDINGS
We categorized all completed and on-going trials on the basis of the specific de-escalated treatment protocol. Several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. Considering the conflicting results reported so far by preliminary studies, it is necessary to wait for the final results of the on-going trials to better clarify which is the best de-intensified strategy and which patients would really benefit from it.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Clinical Trials as Topic; Humans; Oropharyngeal Neoplasms; Radiotherapy; Radiotherapy Dosage
PubMed: 32643045
DOI: 10.1007/s11912-020-00948-1 -
Biochimica Et Biophysica Acta Dec 2016The last decade has brought about an unexpected rise in oropharyngeal squamous cell carcinoma (OPSCC) primarily in white males from the ages of 40-55years, with limited... (Review)
Review
The last decade has brought about an unexpected rise in oropharyngeal squamous cell carcinoma (OPSCC) primarily in white males from the ages of 40-55years, with limited exposure to alcohol and tobacco. This subset of squamous cell carcinoma (SCC) has been found to be associated with human papillomavirus infection (HPV). Other Head and Neck Squamous Cell carcinoma (HNSCC) subtypes include oral cavity, hypopharyngeal, nasopharyngeal, and laryngeal SCC which tend to be HPV negative. HPV associated oropharyngeal cancer has proven to differ from alcohol and tobacco associated oropharyngeal carcinoma in regards to the molecular pathophysiology, presentation, epidemiology, prognosis, and improved response to chemoradiation therapy. Given the improved survival of patients with HPV associated SCC, efforts to de-intensify treatment to decrease treatment related morbidity are at the forefront of clinical research. This review will focus on the important differences between HPV and tobacco related oropharyngeal cancer. We will review the molecular pathogenesis of HPV related oropharyngeal cancer with an emphasis on new paradigms for screening and treating this disease.
Topics: Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Virus Internalization
PubMed: 27487173
DOI: 10.1016/j.bbcan.2016.07.005