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Dhar L, Singh S, Passey JC. Association of human papillomavirus and Epstein-Barr virus with squamous cell carcinoma of upper aerodigestive tract. Natl J Maxillofac Surg 2022; 13:367-375. [PMID: 36683943 PMCID: PMC9851353 DOI: 10.4103/njms.njms_315_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/09/2021] [Accepted: 05/20/2021] [Indexed: 01/24/2023] Open
Abstract
Background Cancers of the upper aero-digestive tract (UADT) are fifth most common cancer in the world with around 10,55,000 new cases and 7,25,000 deaths worldwide. Tobacco and alcohol act synergistically and are the two most important etiological factors responsible for about 75% of SCC. Studies have reported changing trends in the incidence of SCC showing an increasing shift in epidemiology attributed to the infection by viruses. The most commonly implicated viruses are the Human Papillomavirus (HPV) and Epstein-Barr virus (EBV). Aim and Objective To study association of Human Papilloma virus (HPV) and Epstein Barr virus (EBV) with 100 newly diagnosed cases of squamous cell carcinoma (SCC) of upper aerodigestive tract (UADT) and correlate its association with clinical parameters, histomorphological grade and staging using immunohistochemical markers p16, LMP1, p53, p63. Materials and Methods The study was conducted in the department of Pathology, Maulana Azad medical college and associated hospitals, New Delhi from September 2018-April 2019. Specimens was routinely processed. Immunohistochemistry (IHC) was done using p16, LMP1, p53, p63 monoclonal antibodies. Statistical Analysis Used SPSS 20 software. The quantitative analysis was done using Pearson chi-square test. Probability values < 0.05 was be considered statistically significant. Results HPV was present in 29% cases while EBV in 38% cases. Oral cavity was the most common site involved by both HPV and EBV. Co-infectivity was found in 4% cases. There was significant male predominance in both. HPV was more prevalent in age >45 years while EBV was equally distributed in <45 years and >45 years. Moderately differentiated squamous cell carcinoma was the commonest grade involved by both the viruses. A significant correlation was found between EBV and alcohol. p53 positivity had an inverse relationship with HPV positivity. P63 expression was higher in HPV and EBV positive cases. Conclusion In resource constraint settings, p16 and Latent membrane protein 1 can be used as surrogacy markers for Human Papilloma virus and Epstein Barr virus along with p53 and p63 for its association with histomorphological grade and stage.
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Affiliation(s)
- Lity Dhar
- Department of Pathology, Otorhinolaryngology, Maulana Azad Medical College, New Delhi, India
| | - Sarika Singh
- Department of Pathology, Otorhinolaryngology, Maulana Azad Medical College, New Delhi, India
| | - J. C. Passey
- Department of Pathology, Otorhinolaryngology, Maulana Azad Medical College, New Delhi, India
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McKeon MG, Gallant JN, Kim YJ, Das SR. It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer. Cancers (Basel) 2022; 14:cancers14133120. [PMID: 35804891 PMCID: PMC9265087 DOI: 10.3390/cancers14133120] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 06/04/2022] [Accepted: 06/21/2022] [Indexed: 12/04/2022] Open
Abstract
Simple Summary Certain viruses, specifically, human papillomavirus (HPV) and Epstein–Barr virus (EBV), have been linked with the development of head and neck cancer. In this study, we review the mechanisms by which (these) viruses lead to cellular transformation and a chronic inflammatory state. Given that the head and neck host a rich microbiome (which itself is intrinsically linked to inflammation), we scrutinize the literature to highlight the interplay between viruses, cellular transformation, inflammation, and the local host microbiome in head and neck cancer. Abstract While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)—a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present (with about 1% of the population having high-risk oral HPV infection at any one time), less than 1% of those infected with high-risk strains develop OPSCC—suggesting that additional cofactors or coinfections may be required. Epstein–Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions—leading to tumor growth.
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Affiliation(s)
- Mallory G. McKeon
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, Medical Center North, Suite A2200, Nashville, TN 37232, USA;
- Department of Otolaryngology—Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (J.-N.G.); (Y.J.K.)
| | - Jean-Nicolas Gallant
- Department of Otolaryngology—Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (J.-N.G.); (Y.J.K.)
| | - Young J. Kim
- Department of Otolaryngology—Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (J.-N.G.); (Y.J.K.)
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Suman R. Das
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, Medical Center North, Suite A2200, Nashville, TN 37232, USA;
- Correspondence: ; Tel.: +1-(615)-322-0322; Fax: +1-(615)-343-6160
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Mudhar HS, Milman T, Zhang PJL, Shields CL, Eagle RC, Lally SE, Shields JA, Salvi SM, Rundle PA, Tan J, Rennie IG. Conjunctival 'mucoepidermoid carcinoma' revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye. Mod Pathol 2020; 33:1242-1255. [PMID: 31932683 DOI: 10.1038/s41379-020-0456-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 12/11/2019] [Accepted: 12/26/2019] [Indexed: 02/08/2023]
Abstract
In 2018, the consensus meeting for the WHO Classification of Tumours of the Eye decided that conjunctival mucoepidermoid carcinoma should be reclassified as adenosquamous carcinoma, as this represented a better morphological fit. To examine the applicability of this terminology, we studied the clinical, histopathological, immunohistochemical and molecular pathology of 14 cases that were originally diagnosed as conjunctival mucoepidermoid carcinoma. There were 7 (50%) females and 7 (50%) males. The median age was 64 years. The left eye was affected in 8 and the right eye in 6 patients. In-situ carcinoma was present in 11/14 (79%) cases and comprised in-situ squamous cell carcinoma (SCC) and conjunctival intraepithelial neoplasia with mucinous differentiation (CIN-Muc). Invasive carcinoma was present in 11/14 (79%) cases. Group 1 (1/11 cases, 9%) comprised invasive SCC only. Group 2 (6/11 cases, 55%) comprised SCC with mucinous differentiation, manifesting as scattered intracellular mucin, occasionally together with intercellular mucin, with no evidence of true glandular differentiation. Group 3 (3/11 cases. 27%) comprised true adenosquamous carcinoma. Group 4 (1/11 cases, 9%) comprised pure adenocarcinoma. Thirteen of 14 cases (93%) underwent FISH for MAML2 translocation and none were rearranged. Two cases harboured high-risk HPV (type 16 and 18). The combined findings confirm that all lesions in our study were not mucoepidermoid carcinoma, but represented predominantly SCC with mucinous differentiation and adenosquamous carcinoma. We, therefore, recommend future revision of the WHO classification to include SCC with mucinous differentiation alongside adenosquamous carcinoma.
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Affiliation(s)
- Hardeep S Mudhar
- National Specialist Ophthalmic Pathology Service (NSOPS), Department of Histopathology, E-Floor, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK.
| | - Tatyana Milman
- Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.,Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA
| | - Paul J L Zhang
- Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Carol L Shields
- Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.,Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA
| | - Ralph C Eagle
- Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.,Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA
| | - Sara E Lally
- Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.,Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA
| | - Jerry A Shields
- Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.,Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA
| | - Sachin M Salvi
- Sheffield Ocular Oncology Service, Department of Ophthalmology, A-Floor, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK
| | - Paul A Rundle
- Sheffield Ocular Oncology Service, Department of Ophthalmology, A-Floor, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK
| | - Jennifer Tan
- Oculoplastic Service, Department of Ophthalmology, A-Floor, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK
| | - Ian G Rennie
- Sheffield Ocular Oncology Service, Department of Ophthalmology, A-Floor, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK
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Mirza S, Hadi N, Pervaiz S, Zeb Khan S, Mokeem SA, Abduljabbar T, Al-Hamoudi N, Vohra F. Expression of HER-2/neu in Oral Squamous Cell Carcinoma. Asian Pac J Cancer Prev 2020; 21:1465-1470. [PMID: 32458657 PMCID: PMC7541867 DOI: 10.31557/apjcp.2020.21.5.1465] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND HER-2/neu is a member of the human epidermal growth factor (HER) family of transmembrane tyrosine kinases, which is significantly associated with the pathogenesis of various cancer types. The aim was to evaluate the expression of HER-2/neu in oral squamous cell carcinoma (OSCC) as a potential biomarker to target antigens for specific immunotherapy in OSCC. METHODS One hundred and forty histologically diagnosed OSCC cases were identified. Four to five-micrometer thick formalin-fixed, paraffin-embedded tumor sections were stained with Haematoxylin and Eosin (H and E). Histological grade was assessed according to WHO/Broders classification, while tumors were staged according to the American Joint Committee on Cancer (AJCC) TNM classification from stage I to IV. Immunohistochemistry was performed by using Rabbit monoclonal antibody against HER-2/neu (EP700Y, cell marquee and diluted 1:50). FISH was performed on positive cases using Vysis PathVysion HER-2 DNA probe (Abbott USA). Probes consist of LSI HER gene spectrum orange and control probe CEP 17 spectrum green. RESULTS In this study, males were mostly effected (64.3%) with buccal mucosa (49%) to be the commonly involved site for OSCC. Majority of cases were moderately differentiated (62.1%) and 50.7% tumors were Stage IV. HER-2/neu was found to be positive (2+) in one case of OSCC, however weak to moderate complete membrane staining was observed in >10% of the tumor cells. One hundred and thirty nine cases were HER-2/neu negative. FISH analysis of HER-2/neu positive cases also showed gene amplification (Her2-neu/ CEp 17 = 225/33 = 7.2). CONCLUSIONS The study showed disparity in the expression of HER-2/neu in OSCC, which is due to multiple reasons. Therefore therapy against HER-2/neu in OSCC is debatable.
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Affiliation(s)
- Sana Mirza
- Department of Oral Pathology, College of Dentistry, Ziauddin Medical University, Karachi, Pakistan
| | - Naila Hadi
- Research and Development, Islamabad Medical and Dental College, Shaheed Zulfiqar Ali Bhutto Medical University, Ilamabad, Pakistan
| | - Shahid Pervaiz
- Department of Histopathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan
| | - Sultan Zeb Khan
- Department of Clinical Pathophysiology, Graduate School of Tokyo Dental College, 1-2-2 Masago, Mihama-Ku, Chiba 261-8502, Japan
| | - Sameer A Mokeem
- Department of Periodontics and Community Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Tariq Abduljabbar
- Department of Prosthetic Dental Science, College of Dentistry, King Saud University, Research Chair for Biological Research in Dental Health, Riyadh, Saudi Arabia
| | - Nawwaf Al-Hamoudi
- Department of Periodontics and Community Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Fahim Vohra
- Department of Prosthetic Dental Science, College of Dentistry, King Saud University, Research Chair for Biological Research in Dental Health, Riyadh, Saudi Arabia
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Devaraja K, Aggarwal S, Verma SS, Gupta SC. Clinico-pathological peculiarities of human papilloma virus driven head and neck squamous cell carcinoma: A comprehensive update. Life Sci 2020; 245:117383. [PMID: 32007572 DOI: 10.1016/j.lfs.2020.117383] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/17/2020] [Accepted: 01/28/2020] [Indexed: 01/11/2023]
Abstract
AIMS The current article provides a detailed account of the current understanding of molecular and clinico-pathological aspects of Human papilloma virus (HPV) driven head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS The literature review included most of the landmark trials and clinical studies related to the HPV driven HNSCC. KEY FINDINGS HPV positive HNSCC differ distinctly from HPV negative tobacco-related HNSCC, especially in oropharyngeal region. Therefore, the American joint committee on cancer`s latest manual for classification and staging of cancer suggests a separate staging system for HPV positive oropharyngeal cancers. Despite the younger patients being affected and the high propensity for cervical metastasis, the HPV positive oropharyngeal cancers respond much better to the treatment. The association with wild type TP53 and low EGFR expression confers the favorable prognosis in HPV driven HNSCC. Since the association is not universal, we suggest checking for p53 and EGFR expression status before considering de-intensification of therapy. In addition, the presence of matted lymph nodes and five or more nodes could mean relatively poorer prognosis, and are not suitable for de-intensification of therapy. The same is also true probably with higher T stage and co-existing tobacco use. The methods for the detection of p16, HPV DNA, HPV E6/E7 mRNA, anti-E6/E7 antibodies, in tissue, in serum and in saliva of patients, along with their clinical implications are also discussed. SIGNIFICANCE This article provides latest developments on the HPV driven HNSCC. 'Diagnosis of transcriptionally active HPV infection,' 'Modalities for surveillance,' 'Implication of de-escalation of therapy' are some of the critical issues that could serve the medical, the research as well as the patient communities.
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Affiliation(s)
- K Devaraja
- Department of Otorhinolaryngology and Head and Neck surgery, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, 576104, India.
| | - Sadhna Aggarwal
- Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Sumit Singh Verma
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221 005, India
| | - Subash Chandra Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221 005, India.
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Fernández-López C, Morales-Angulo C. Otorhinolaryngology Manifestations Secondary to Oral Sex. ACTA ACUST UNITED AC 2017. [DOI: 10.1016/j.otoeng.2016.04.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Ashraf MJ, Hosseini S, Monabati A, Valibeigi B, Khademi B, Abedi E, Azarpira N. The Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of Oral Tongue. IRANIAN JOURNAL OF PATHOLOGY 2017. [PMID: 29515636 PMCID: PMC5831070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND OBJECTIVE Oral tongue Squamous Cell carcinoma (SCC) commonly involves males between the sixth to eighth decades of life. Major risk factors are tobacco usage and alcohol consumption. The increasing number of patients developing oral tongue cancer without these well-known risk factors suggests that a viral infection, such as Human Papillomavirus (HPV), may be responsible for this increase, by acting as an oncogenic agent. This study investigated the prevalence of HPV infection and its clinicopathologic significance in oral tongue SCCs. METHODS Tissue blocks from a total of 50 cases (patients with oral tongue SCC) and 50 controls (palatine tonsillar tissues with benign diagnosis) were selected. DNA was extracted from tumoral and non-tumoral tissue blocks. Detection of common HPV DNA by nested Polymerase Chain Reaction (PCR), and high-risk genotypes, HPV 16 and HPV 18, by conventional PCR, was achieved and the results correlated with clinicopathological parameters. RESULTS Of the 50 patients (18 males and 32 females with a mean age of 57.36±12.18 years, and age range of 27 to 86 years), 7 (14%) had HPV positive results. None of the control group subjects had HPV DNA positive results (P-value of 0.012). The HPV genotype 16/18 was not detected in positive cases. No statistically significant association was found between HPV status and gender, age, tumor grade, tumor stage or lymph node involvement. CONCLUSION Although there was a significantly higher prevalence of HPV in oral tongue SCC, its association with carcinogenesis in this area requires further studies.
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Affiliation(s)
| | - Shahla Hosseini
- Pathology Department, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahmad Monabati
- Pathology Department, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Behnaz Valibeigi
- Pathology Department, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bijan Khademi
- Otolaryngology Department, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Elham Abedi
- Pathology Department, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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8
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Fernández-López C, Morales-Angulo C. Otorhinolaryngology manifestations secondary to oral sex. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2016; 68:169-180. [PMID: 27793330 DOI: 10.1016/j.otorri.2016.04.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 04/13/2016] [Accepted: 04/17/2016] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Over the last few years, oral and pharyngeal signs and symptoms due to oral sex have increased significantly. However, no review articles related to this subject have been found in the medical literature. The objective of our study was to identify otorhinolaryngological manifestations associated with orogenital/oroanal contact, both in adults and children, in the context of consensual sex or sexual abuse. METHODS We performed a review of the medical literature on otorhinolaryngological pathology associated with oral sex published in the last 20 years in the PubMed database. RESULTS Otorhinolaryngological manifestations secondary to oral sex practice in adults can be infectious, tumoral or secondary to trauma. The more common signs and symptoms found in the literature were human papillomavirus infection (above all, condyloma acuminata and papilloma/condyloma), oral or pharyngeal syphilis, gonococcal pharyngitis, herpes simplex virus infection and pharyngitis from Chlamydia trachomatis. The incidence of human papillomavirus -induced oropharyngeal carcinoma has dramatically increased. In children past the neonatal period, the presence of condyloma acuminatus, syphilis, gonorrhoea or palatal ecchymosis (the last one, unless justified by other causes) should make us suspect sexual abuse. CONCLUSIONS Sexual habits have changed in the last decades, resulting in the appearance of otorhinolaryngological pathology that was rarely seen previously. For this reason, it is important for primary care physicians to have knowledge about the subject to perform correct diagnosis and posterior treatment. Some sexual abuse cases in children may also be suspected based on the knowledge of the characteristic oropharyngeal manifestations secondary to them.
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Affiliation(s)
- Claudia Fernández-López
- Servicio de Otorrinolaringología, Facultad de Medicina, Universidad de Cantabria, HUMV Santander, IDIVAL, Cantabria, Santander, España
| | - Carmelo Morales-Angulo
- Servicio de Otorrinolaringología, Facultad de Medicina, Universidad de Cantabria, HUMV Santander, IDIVAL, Cantabria, Santander, España.
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Tsimplaki E, Argyri E, Sakellaridis A, Kyrodimos E, Xesfyngi D, Panotopoulou E. Oropharyngeal and laryngeal but not oral cancers are strongly associated with high-risk human papillomavirus in 172 Greek patients. J Med Virol 2016; 89:170-176. [PMID: 27335246 DOI: 10.1002/jmv.24614] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2016] [Indexed: 11/07/2022]
Abstract
A strong and consistent association has been reported between human papillomavirus (HPV) infection and oropharyngeal cancer, whereas a similar link has not yet been clarified in oral and laryngeal cancer. The purpose of this study was to investigate the association between HPV infection and head and neck squamous cell carcinoma (HNSCC) in Greek patients. Cytological or tissue specimens from 172 cases patients with HNSCC and cytological specimens from 91 control subjects were analyzed for HPV DNA detection and genotyping using a microarray-based assay. Multivariate logistic regression was used to estimate odds ratios (ORs) for the association between the presence of HPV infection and HNSCC for each of the tumor site, after adjustment for potential confounders. The adjusted ORs for positivity to high-risk HPV infection for oropharyngeal and laryngeal cancer were 20.3 (95% CI: 1.7-250.1) and 22.8 (95% CI: 2.5-206.2), respectively. High-risk HPV infection was not significantly associated with oral cancer. HPV infection was independently associated with poorly differentiated tumors (OR = 2.8; 95% CI: 1.1-7.5). Our results suggest a strong association of high-risk HPV infection with oropharyngeal and laryngeal cancer. J. Med. Virol. 89:170-176, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Elpida Tsimplaki
- Department of Virology, "St. Savvas" Regional Anticancer Oncology Hospital of Athens, Athens, Greece
| | - Elena Argyri
- Department of Virology, "St. Savvas" Regional Anticancer Oncology Hospital of Athens, Athens, Greece
| | - Athanassios Sakellaridis
- Department of Otolaryngology, Head and Neck Surgery, "St. Savvas" Regional Anticancer Oncology Hospital of Athens, Athens, Greece
| | - Efthimios Kyrodimos
- Department of Otolaryngology, Head and Neck Surgery, "Hippokration" General Hospital, National University of Athens, Athens, Greece
| | - Dimitra Xesfyngi
- Department of Radiotherapy, "St. Savvas" Regional Anticancer Oncology Hospital of Athens, Athens, Greece
| | - Efstathia Panotopoulou
- Department of Virology, "St. Savvas" Regional Anticancer Oncology Hospital of Athens, Athens, Greece.
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Saghravanian N, Zamanzadeh M, Meshkat Z, Afzal Aghaee M, Salek R. Evaluation of the Prevalence Rate and the Prognostic Effect of Human Papilloma Virus Infection in a Group of Patients With Oral Cavity Squamous Cell Carcinoma. IRANIAN JOURNAL OF CANCER PREVENTION 2016; 9:e3998. [PMID: 27703640 PMCID: PMC5038837 DOI: 10.17795/ijcp-3998] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 03/14/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Squamous cell carcinoma (SCC) is the most common malignancy of the oral cavity. A relationship between the human papilloma virus (HPV) infection and the prognosis of oral cavity SCC (OCSCC) has been discussed before. OBJECTIVES We investigated the prevalence rate of HPV status in patients with OCSCC, and its effects on clinicopathological characteristics of tumors and patients' prognosis. PATIENTS AND METHODS Sections of formalin-fixed, paraffin-embedded tissue blocks from 114 histopathologically confirmed OCSCC cases were investigated in this study. Polymerase chain reaction (PCR) was applied to evaluate the HPV status in the samples. RESULTS Fifteen (13.16%) cases were identified as HPV positive. The detected viral subtypes in this study were the subtypes 6 and 11. The stage and especially lymph node stage was significantly higher in the HPV positive group compared to the HPV negative group (P = 0.04). Disease free survival (DFS) was remarkably lower in the HPV positive group compared to the HPV negative group (13.9 vs. 49.9 months, P = 0.02). Overall survival (OS) was also significantly inferior in the HPV positive group (15.7 vs. 49.6 months, P = 0.01). In the current study, no significant differences were observed between two groups in relation to the variables of age, gender, tumors site, tumor size, tumor grading and also the recurrence rate. CONCLUSIONS The observed higher mortality rate among the HPV positive group indicates the poorer prognosis of this group in comparison with the HPV negative patients. The incidence rate of HPV infection was low in the studied samples; however, interaction of subtypes 6 and 11 of HPV in poorer prognosis of the patients and a carcinogenic role of HPV in OCSCC cannot be ruled out.
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Affiliation(s)
- Nasrollah Saghravanian
- Department of Oral and Maxillofacial Pathology, Dental Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Maryam Zamanzadeh
- Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mazandaran University of Medical Sciences, Sari, IR Iran
| | - Zahra Meshkat
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Monavar Afzal Aghaee
- Department of Community Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Roham Salek
- Clinical Radiation Oncology, Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran
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Woods RSR, O’Regan EM, Kennedy S, Martin C, O’Leary JJ, Timon C. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review. World J Clin Cases 2014; 2:172-193. [PMID: 24945004 PMCID: PMC4061306 DOI: 10.12998/wjcc.v2.i6.172] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Revised: 04/21/2014] [Accepted: 05/19/2014] [Indexed: 02/05/2023] Open
Abstract
Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.
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Woo SB, Cashman EC, Lerman MA. Human papillomavirus-associated oral intraepithelial neoplasia. Mod Pathol 2013; 26:1288-97. [PMID: 23599160 DOI: 10.1038/modpathol.2013.70] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Revised: 02/17/2013] [Accepted: 02/19/2013] [Indexed: 02/03/2023]
Abstract
This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer.
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Affiliation(s)
- Sook-Bin Woo
- 1] Harvard School of Dental Medicine, Boston, MA, USA [2] Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA [3] Strata Pathology Services, Cambridge, MA, USA
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Bates T, McQueen A, Iqbal MS, Kelly C, Robinson M. Small cell neuroendocrine carcinoma of the oropharynx harbouring oncogenic HPV-infection. Head Neck Pathol 2013; 8:127-31. [PMID: 23838856 PMCID: PMC3950381 DOI: 10.1007/s12105-013-0471-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 06/27/2013] [Indexed: 01/16/2023]
Abstract
Small cell carcinoma/neuroendocrine carcinoma (SCNEC) of the oropharynx is uncommon. Recently, an association has been reported between oropharyngeal SCNEC and high-risk human papillomavirus (HPV) infection. While HPV infection confers a better prognosis for oropharyngeal squamous cell carcinoma, HPV infection does not appear to influence the biological behaviour of SCNECs, which are generally associated with poor clinical outcomes. We document two cases of SCNEC arising in the oropharynx with evidence of high-risk HPV infection. The cases highlight the expanding range of malignant oropharyngeal neoplasms that harbour oncogenic HPV infection and support the concept that, irrespective of HPV infection, neuroendocrine differentiation portends a poor prognosis.
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Affiliation(s)
- Timothy Bates
- Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
| | - Andrew McQueen
- Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
| | | | - Charles Kelly
- Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
| | - Max Robinson
- Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
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Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, Roberts S. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer--systematic review and meta-analysis of trends by time and region. Head Neck 2012; 35:747-55. [PMID: 22267298 DOI: 10.1002/hed.22015] [Citation(s) in RCA: 610] [Impact Index Per Article: 46.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Revised: 02/23/2011] [Accepted: 10/12/2011] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Little information has been reported on regional and time trends of human papillomavirus (HPV) prevalence rates of oropharyngeal cancer (OPC) and non-OPC. METHODS The study consisted of a systematic review and meta-analysis using random effects logistic regression models. RESULTS Overall HPV prevalence in OPC (47.7%; 95% confidence interval [CI], 42.9-52.5%) increased significantly over time: from 40.5% (95% CI, 35.1-46.1) before 2000, to 64.3% (95% CI, 56.7-71.3) between 2000 and 2004, and 72.2% (95% CI, 52.9-85.7) between 2005 and 2009 (p < .001). Prevalence increased significantly in North America and Europe, and the significant gap between them that existed before 2000 (50.7% vs 35.3%, respectively, p = .008) has now disappeared (69.7% vs 73.1%, respectively, p = .8). Prevalence in non-OPC (21.8%; 95% CI, 18.9-25.1%) has not increased over time (p = .97). CONCLUSIONS The sharp increase in the proportion of HPV-positive OPC over the last decade has occurred at a faster rate in Europe compared with that in North America. In contrast, the relatively low prevalence of HPV in non-OPC remains unchanged.
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Affiliation(s)
- Hisham Mehanna
- Institute of Head and Neck Studies and Education, Coventry, United Kingdom.
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Kabeya M, Furuta R, Kawabata K, Takahashi S, Ishikawa Y. Prevalence of human papillomavirus in mobile tongue cancer with particular reference to young patients. Cancer Sci 2011; 103:161-8. [DOI: 10.1111/j.1349-7006.2011.02149.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
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GRIM-19 disrupts E6/E6AP complex to rescue p53 and induce apoptosis in cervical cancers. PLoS One 2011; 6:e22065. [PMID: 21765936 PMCID: PMC3134474 DOI: 10.1371/journal.pone.0022065] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2011] [Accepted: 06/14/2011] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Our previous studies showed a down-regulation of GRIM-19 in primary human cervical cancers, and restoration of GRIM-19 induced tumor regression. The induction of tumor suppressor protein p53 ubiquitination and degradation by E6 oncoportein of high risk-HPV through forming a stable complex with E6AP is considered as a critical mechanism for cervical tumor development. The aims of this study were to determine the potential role of GRIM-19 in rescuing p53 protein and inducing cervical cancer cell apoptosis. METHODOLOGY/PRINCIPAL FINDINGS The protein levels of GRIM-19 and p53 were detected in normal cervical tissues from 45 patients who underwent hysterectomy for reasons other than neoplasias of either the cervix or endometrium, and cervical cancer tissues from 60 patients with non-metastatic squamous epithelial carcinomas. Coimmunoprecipitation and GST pull-down assay were performed to examine the interaction of GRIM-19 with 18E6 and E6AP in vivo and in vitro respectively. The competition of 18E6 with E6AP in binding GRIM-19 by performing competition pull-down assays was designed to examine the disruption of E6/E6AP complex by GRIM-19. The augment of E6AP ubiquitination by GRIM-19 was detected in vivo and in vitro ubiquitination assay. The effects of GRIM-19-dependent p53 accumulation on cell proliferation, cell cycle, apoptosis were explored by MTT, flow cytometry and transmission electron microscopy respectively. The tumor suppression was detected by xenograft mouse model. CONCLUSION/SIGNIFICANCE The levels of GRIM-19 and p53 were concurrently down regulated in cervical cancers. The restoration of GRIM-19 can induce ubiquitination and degradation of E6AP, and disrupt the E6/E6AP complex through the interaction of N-terminus of GRIM-19 with both E6 and E6AP, which protected p53 from degradation and promoted cell apoptosis. Tumor xenograft studies also revealed the suppression of p53 degradation in presence of GRIM-19. These data suggest that GRIM-19 can block E6/E6AP complex; and synergistically suppress cervical tumor growth with p53.
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Papillomas of the external ear canal: report of ten cases in Chinese patients with HPV in situ hybridization. Head Neck Pathol 2009; 3:207-11. [PMID: 20596973 PMCID: PMC2811635 DOI: 10.1007/s12105-009-0131-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2009] [Accepted: 07/19/2009] [Indexed: 12/14/2022]
Abstract
Squamous papilloma is a benign exophytic proliferation which can occur occasionally in the external ear canal. It is widely assumed that the Human Papilloma Virus (HPV) is an etiologic factor of papillomas. Available techniques for detection of HPV genomes include immunohistochemistry, Southern blot hybridization, in situ hybridization (ISH), and polymerase chain reaction. To our knowledge, HPV typing has not been reported on tissue sections of papillomas in the external ear canal. We report HPV ISH analysis in ten cases of papillomas, involving the external ear canal in Chinese patients. These papilloma excrescences were less than 1 cm in diameter, and were benign morphologically. Automated HPV ISH analysis was performed for the hybridization of DNA probes, including both low-risk and high-risk HPV subtypes. HPV ISH results revealed that seven out of ten cases were positive for low-risk HPV (6, 11), three cases demonstrated no hybridization for low-risk HPV probe, and none of the cases revealed any detection of high-risk HPV (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, and 66). On follow-up after 18-29 months (average 24.5 months), eight patients were doing well, with no local recurrence after excision. Two patients were lost to follow-up. Our results confirm that benign papillomas of the external ear canal are associated with low-risk HPV infection with benign behavior and neither recurrence nor high grade dysplasia.
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