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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 -
Journal of Otolaryngology - Head & Neck... Sep 2018Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has an improved outcome and may allow for treatment de-escalation. High-risk HPV...
BACKGROUND
Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has an improved outcome and may allow for treatment de-escalation. High-risk HPV (HR-HPV) infection is associated with deregulated expression of the cell cycle-associated proteins p16, pRB, cyclin D1 and p53. The objective of this study was to assess cell cycle proteins as potential surrogate markers for HR-HPV DNA testing to identify OPSCC with favorable prognosis after resection.
METHODS
Tissue microarray cores of 313 surgically treated OPSCC were stained for p16, pRB, cyclin D1 and p53 using immunohistochemistry. Protein expression was scored as high or low based on the proportion of positive carcinoma cells. Tumor samples were analysed for HR-HPV DNA with polymerase chain reaction-based testing. Associations between cell cycle protein expression and HR-HPV DNA status were evaluated by calculating sensitivity, specificity, predictive values, and diagnostic odds ratios (DOR). Kaplan-Meier and Cox regression analysis were applied to evaluate associations between cell cycle protein expression and patient outcome.
RESULTS
High expression of p16, cyclin D1, pRB and p53 in tumor cells were observed in 51.8%, 51.4%, 41.9% and 33.5% of OPSCC, respectively. HR-HPV DNA positive were 158/313 (50.5%) tumor samples (HPV16: 147, HPV18: 1, HPV33: 5, HPV35: 2, HPV56: 2, and HPV59: 1). P16 showed a higher DOR to predict HR-HPV DNA positivity than pRB, cyclin D1 and p53. Both the p16/pRB and the p16/pRB/cyclin D1/p53 signatures had lower DOR than p16 alone. Improved 5-year overall and disease-specific survival were associated with HR-HPV DNA positivity, high p16, low pRB, low cyclin D1, and low p53 expression. Associations with improved outcome were also observed for the marker combinations high p16/positive HR-HPV DNA, high p16/low pRB and high p16/low pRB/low cyclin D1/low p53. In a multivariate analysis adjusted for age, smoking history, pT and pN category, high p16 expression showed the lowest hazard ratio for death.
CONCLUSIONS
High p16 expression is a reliable marker for survival prognostication in surgically treated OPSCC patients. Protein signatures including the pRB, cyclin D1 and p53 proteins do not further increase the prognostic performance of p16 as a single marker.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Cycle; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Human papillomavirus 16; Humans; Immunohistochemistry; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomavirus Infections; Polymerase Chain Reaction; Prognosis; Salivary Proline-Rich Proteins; Tumor Suppressor Protein p53
PubMed: 30189895
DOI: 10.1186/s40463-018-0298-3 -
Cancer Medicine Feb 2016Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor tyrosine kinase family. It has been identified as a promising...
Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor tyrosine kinase family. It has been identified as a promising therapeutic target in multiple types of cancer. We have investigated FGFR3 protein expression and FGFR3 gene copy-numbers in a single well-documented cohort of oral and oropharyngeal squamous cell carcinoma. Tissue microarray sets containing 452 formalin-fixed paraffin-embedded tissues were immunohistochemically stained with an anti-FGFR3 antibody and hybridized with a FGFR3 fluorescence in situ hybridization probe. FGFR3 protein expression was correlated with clinicopathological and survival data, which were retrieved from electronic medical records. FGFR3 mRNA data of 522 head and neck squamous cell carcinoma (HNSCC) were retrieved from The Cancer Genome Atlas (TCGA). Fibroblast growth factor receptor 3 (FGFR3) protein was overexpressed in 48% (89/185) of oral and 59% (124/211) of oropharyngeal squamous cell carcinoma. Overexpression of FGFR3 protein was not related to overall survival or disease-free survival in oral (HR[hazard ratio]: 0.94; 95% CI: 0.64-1.39; P = 0.77, HR: 0.94; 95% CI: 0.65-1.36; P = 0.75) and oropharyngeal squamous cell carcinoma (HR: 1.21; 95% CI: 0.81-1.80; P = 0.36, HR: 0.42; 95% CI: 0.79-1.77; P = 0.42). FGFR3 mRNA was upregulated in 3% (18/522) of HNSCC from the TCGA. The FGFR3 gene was gained in 0.6% (1/179) of oral squamous cell carcinoma but no amplification was found in oral and oropharyngeal squamous cell carcinoma. In conclusion, FGFR3 protein is frequently overexpressed in oral and oropharyngeal squamous cell carcinoma. Therefore, it may serve as a potential therapeutic target for FGFR3-directed therapies in oral and oropharyngeal squamous cell carcinoma.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Gene Dosage; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Oropharyngeal Neoplasms; Prognosis; Proportional Hazards Models; RNA, Messenger; Receptor, Fibroblast Growth Factor, Type 3
PubMed: 26711175
DOI: 10.1002/cam4.595 -
European Archives of... Mar 2019The aim of this study was to evaluate the 8th edition of the American Joint Committee on Cancer Staging Manual: Head and Neck Section on oropharyngeal squamous cell...
PURPOSE
The aim of this study was to evaluate the 8th edition of the American Joint Committee on Cancer Staging Manual: Head and Neck Section on oropharyngeal squamous cell cancer (OPSCC) and to clarify the relationship between p16 overexpression and the presence of human papillomavirus (HPV) DNA using fresh frozen samples.
METHODS
Samples from 100 OPSCC patients were analyzed using polymerase chain reaction (PCR) and p16 immunohistochemistry.
RESULTS
Five-year overall survival (OS) was 73.0%, 93.9%, and 62.2% in all, p16-positive (n = 34), and p16-negative (n = 66) cases, respectively. OS tended to be better aligned with stage in the 8th edition than in the 7th edition. The 5-year OS was 96.0% in never or light smokers (< 40 pack-years), and 87.5% in heavy smokers (≥ 40 pack-years) in the p16-positive group, respectively (p = 0.027). HPV infection was found in 100% of p16-positive and 21.2% of p16-negative cases. The p16-positive cases had higher viral load and integrated physical status than the p16-negative cases. Although 1 case with p16 overexpression showed no PCR amplification using consensus primers, PCR amplification was detected using HPV 16 E6-specific primers.
CONCLUSIONS
The 8th edition predicts OPSCC prognosis more accurately than the 7th edition and p16-overexpression is an excellent surrogate marker for detecting HPV infection. Although high-risk-type HPV infection was observed in p16-negative cases, it showed no significant effect in survival outcome.
Topics: Adult; Aged; DNA, Neoplasm; Female; Human papillomavirus 16; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomavirus Infections; Polymerase Chain Reaction; Prognosis; Smokers; United States
PubMed: 30594962
DOI: 10.1007/s00405-018-05263-x -
Modern Pathology : An Official Journal... Jan 2017As the human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma epidemic has developed in the past several decades, it has become clear that these tumors... (Review)
Review
As the human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma epidemic has developed in the past several decades, it has become clear that these tumors have a wide variety of morphologic tumor types and features. For the practicing pathologist, it is critical to have a working knowledge about these in order to make the correct diagnosis, not to confuse them with other lesions, and to counsel clinicians and patients on their significance (or lack of significance) for treatment and outcomes. In particular, there are a number of pitfalls and peculiarities regarding HPV-related tumors and their nodal metastases that can easily result in misclassification and confusion. This article will discuss the various morphologic types and features of HPV-related oropharyngeal carcinomas, specific differential diagnoses when challenging, and, if established, the clinical significance of each finding.
Topics: Carcinoma, Squamous Cell; Humans; Lymphatic Metastasis; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections
PubMed: 28060372
DOI: 10.1038/modpathol.2016.152 -
Ear, Nose, & Throat Journal Jun 2013A 52-year old man was referred to our service for evaluation after being diagnosed with oropharyngeal squamous cell carcinoma. Contrast-enhanced computed tomography (CT)... (Review)
Review
A 52-year old man was referred to our service for evaluation after being diagnosed with oropharyngeal squamous cell carcinoma. Contrast-enhanced computed tomography (CT) revealed a mass in the left tonsillar pillar, as well as submental lymphadenopathy. The extent of tumor infiltration was assessed by fluoro-2-deoxyglucose positron emission tomography scans, which showed increased uptake in the tumor bed and a suspicious-looking lymph node near the right hilum. No other signs or symptoms of distant metastasis were evident at that time, and the patient was treated with induction chemotherapy followed by chemoradiation. Several weeks after treatment completion, the patient returned, complaining of right medial foot edema. CT of the right lower extremity revealed multiple high-attenuation masses in the soft tissues of the right leg and foot, including a mass in the medial plantar region of the foot. Approximately 15 to 20% of patients with oropharyngeal squamous cell carcinoma develop distant metastasis throughout the course of the disease. Soft-tissue metastases from oropharyngeal cancers are rare, however, particularly when they present in the absence of widespread metastasis. A review of the current head and neck tumor literature describes soft-tissue metastases in less than 10% of patients with known distant metastases. Metastasis to distal regions such as the lower extremities has rarely been observed but should be included in the differential diagnosis for patients presenting with lower-extremity pain or edema.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Foot; Humans; Leg; Male; Middle Aged; Oropharyngeal Neoplasms; Positron-Emission Tomography; Soft Tissue Neoplasms; Tomography, X-Ray Computed
PubMed: 23780603
DOI: 10.1177/014556131309200621 -
Journal of Otolaryngology - Head & Neck... Aug 2017Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in...
Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options.
BACKGROUND
Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation. However, the EZH2 pathway is amenable to low toxicity therapies designed to promote differentiation to a more benign state and prevent recurrent disease by inhibiting the incorporation of HPV into the genome. This is the first study using clinical specimens to demonstrate EZH2 protein expression in oropharyngeal carcinoma (OPC).
METHODS
The study included eight patients with oropharyngeal carcinoma, confirmed p16INK4a- positive by immunohistochemistry (IHC). The tissue expression of E6/E7 messenger RNA (mRNA) was measured by RNAscope® in-situ hybridization technology. Expression of EZH2, Ki-67, and mitotic indices were assessed by morphoproteomic analysis. Biomedical analytics expanded the results with data from Ingenuity Pathway Analysis (IPA) and KEGG databases to construct a molecular network pathway for further insights.
RESULTS
Expression of E6 and E7 oncogenes in p16INK4a- positive oropharyngeal carcinoma was confirmed. EZH2 and its correlates, including elevated proliferation index (Ki-67) and mitotic progression were also present. Biomedical analytics validated the relationship between HPV- E6 and E7 and the expression of the EZH2 pathway.
CONCLUSION
There is morphoproteomic and mRNA evidence of the association of p16INK4a-HPV infection with the E6 and E7 oncogenes and the expression of EZH2, Ki-67 and mitotic progression in oropharyngeal carcinoma. The molecular network biology was confirmed by biomedical analytics as consistent with published literature. This is significant because the biology lends itself to targeted therapeutic options using metformin, curcumin, celecoxib and sulforaphane as therapeutic strategies to prevent progression or recurrence of disease.
Topics: Aged; Biopsy, Needle; Enhancer of Zeste Homolog 2 Protein; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Male; Molecular Targeted Therapy; Oncogene Proteins, Viral; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus E7 Proteins; Papillomavirus Infections; Prognosis; Proteomics; RNA, Messenger; Repressor Proteins; Sampling Studies; Treatment Outcome; Tumor Virus Infections
PubMed: 28818106
DOI: 10.1186/s40463-017-0230-2 -
Oral and Maxillofacial Surgery Clinics... May 2014Head and neck squamous cell carcinoma is the sixth most common cancer worldwide predominately associated with tobacco use. Changing cause and increased incidence in... (Review)
Review
Head and neck squamous cell carcinoma is the sixth most common cancer worldwide predominately associated with tobacco use. Changing cause and increased incidence in oropharyngeal carcinomas is associated with high-risk types of human papilloma virus and has an improved survival. Optical devices may augment visual oral examination; however, their lack of specificity still warrants tissue evaluation/biopsy. Histologic factors of oral carcinomas are critical for patient management and prognostic determination. Clinical biomarkers are still needed to improve early detection, predict malignant transformation, and optimize therapies.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Diagnostic Imaging; Head and Neck Neoplasms; Humans; Incidence; Mouth Diseases; Oropharyngeal Neoplasms; Papillomaviridae; Predictive Value of Tests; Risk Factors; Tobacco Use Disorder
PubMed: 24794262
DOI: 10.1016/j.coms.2014.01.001 -
Clinical Oral Investigations Mar 2022This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral...
OBJECTIVES
This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral carcinomas, as well as for the diagnosis of tumoral persistence after treatment.
MATERIAL AND METHODS
Seventy-five patients with suspicion of squamous cell carcinoma of the oropharynx or oral cavity were included. Two different study groups were analyzed according to the date of the sample collection: (1) during the first endoscopy exploration and (2) in the first control endoscopy after treatment for squamous cell carcinoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy diagnosis as well as for HPV-DNA detection on brush cytologies were assessed.
RESULTS
Before treatment, the brush cytology showed a sensitivity of 88%, specificity of 100%, and accuracy of 88%. After treatment, it showed a sensitivity of 71%, specificity of 77%, and accuracy of 75%. HPV-DNA detection in cytology samples showed a sensitivity of 85%, specificity of 100%, and accuracy of 91% before treatment and an accuracy of 100% after treatment.
CONCLUSIONS
Liquid-based brush cytology showed good accuracy for diagnosis of oropharyngeal and oral squamous cell carcinoma before treatment, but its value decreases after treatment. Nevertheless, it is useful for HPV-DNA detection, as well as to monitor the patients after treatment.
CLINICAL RELEVANCE
Brush cytology samples are reliable for the detection of HPV-DNA before and after treatment and may be a useful method to incorporate in the HPV testing guidelines.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Mouth Neoplasms; Oropharyngeal Neoplasms; Oropharynx; Papillomavirus Infections; Sensitivity and Specificity
PubMed: 34839418
DOI: 10.1007/s00784-021-04228-5 -
Physica Medica : PM : An International... Feb 2015The purpose of this study is to evaluate the treatment plan adequacy and delivery efficiency among volumetric-modulated arc therapy (VMAT) with one or two arcs and the... (Comparative Study)
Comparative Study
The purpose of this study is to evaluate the treatment plan adequacy and delivery efficiency among volumetric-modulated arc therapy (VMAT) with one or two arcs and the conventional static-field dynamic multileaf collimator (dMLC) intensity-modulated radiation therapy (IMRT) in patients undergoing oropharyngeal carcinoma. Fifteen patient cases were included in this investigation. Each of the cases was planned using step-and-shoot IMRT, VMAT with a single arc (Arc1) and VMAT with double arcs (Arc2). A two-dose level prescription for planning target volumes (PTVs) was delivered with 70 Gy/56 Gy in 30 fractions. Comparisons were performed of the dose-volume histograms (DVH) for PTVs, the DVH for organs at risk (OARs), the monitor units per fraction (MU/fx), and delivery time. IMRT and Arc2 achieved similar target coverage, but superior to Arc1. Apart from the oral cavity, Arc1 showed no advantage in sparing of OARs compared with IMRT, while Arc2 obtained equivalent or better sparing of OARs among the three techniques. VMAT reduced MU/fx and shortened delivery time remarkably compared with IMRT. Our results demonstrated that for oropharyngeal cases, Arc2 can achieve superior target coverage and normal tissue sparing, as well as a significant reduction in treatment time.
Topics: Carcinoma, Squamous Cell; Humans; Organs at Risk; Oropharyngeal Neoplasms; Radiometry; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Time Factors
PubMed: 25284321
DOI: 10.1016/j.ejmp.2014.09.003