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Cui M, Cheng J, Cheng H, Zhao M, Zhou D, Zhang M, Jia J, Luo L. Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis. Arch Oral Biol 2024; 157:105830. [PMID: 37924712 DOI: 10.1016/j.archoralbio.2023.105830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/19/2023] [Accepted: 10/25/2023] [Indexed: 11/06/2023]
Abstract
OBJECTIVE This study aimed to explore the characteristics of human papillomavirus (HPV) in oropharyngeal carcinoma (OPC), in order to provide a new theoretical basis for the prevention, treatment, and management of OPC. METHODS The electronic databases were searched available publications relevant to HPV infection and OPC. Studies were collected until July, 2023. The effect sizes were combined using R 4.2.2 software. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. RESULTS Seventy-one studies were included with 10,908 OPC patients. The pooled prevalence of HPV and HR-HPV infection was 44.22% and 43.94%, respectively. The genotypes of HR-HPV were HPV16 (37.24%), HPV33 (2.44%), HPV18 (1.64%), HPV35 (1.53%), and HPV58 (0.89%). The highest HPV infection was in North America (66.87%), Oceania (43.09%), and Europe (41.49%), lowest in Africa (4.89%). Females exhibited higher HPV infection (43.18% vs 34.59% in males). Top subsites of HPV infection was tonsil (45.78%), followed by base of tongue (36.66%). Infection was higher in OPC patients aged > 60 (38.15%) than < 60 (34.73%). The prevalence of HPV infection in stage I-II of OPC patients is higher than that in stage III-IV. CONCLUSIONS HPV genotyping (16, 18, 33, 35, 58) is a key factor in the prevention and treatment of OPC. Identifying tonsils, base of tongue, and soft palate as common subsites to improve early detection. Elderly women with high HPV infection require attention to risk management and health education for prevention.
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Affiliation(s)
- Meimei Cui
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; Department of Pathology, Weifang Medical University, Weifang, China
| | - Jinling Cheng
- Digestive Department, Shandong Second Provincial General Hospital, Jinan, China
| | - Huijuan Cheng
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
| | - Ming Zhao
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; School of Public Health, Jiamusi University, Jiamusi, China
| | - Dan Zhou
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; School of Public Health, Jiamusi University, Jiamusi, China
| | - Min Zhang
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; School of Public Health, Jiamusi University, Jiamusi, China
| | - Jingjing Jia
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; Department of Basic medicine, Jiamusi University, China
| | - Limei Luo
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China.
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Sharkey Ochoa I, O’Regan E, Toner M, Kay E, Faul P, O’Keane C, O’Connor R, Mullen D, Nur M, O’Murchu E, Barry-O’Crowley J, Kernan N, Tewari P, Keegan H, O’Toole S, Woods R, Kennedy S, Feeley K, Sharp L, Gheit T, Tommasino M, O’Leary JJ, Martin CM. The Role of HPV in Determining Treatment, Survival, and Prognosis of Head and Neck Squamous Cell Carcinoma. Cancers (Basel) 2022; 14:4321. [PMID: 36077856 PMCID: PMC9454666 DOI: 10.3390/cancers14174321] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/29/2022] [Accepted: 09/01/2022] [Indexed: 12/02/2022] Open
Abstract
Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV's involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV's impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention.
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Affiliation(s)
- Imogen Sharkey Ochoa
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
| | - Esther O’Regan
- Trinity St James Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland
- Discipline of Histopathology, St. James’ University Hospital, Trinity College Dublin, D08 NHY1 Dublin, Ireland
| | - Mary Toner
- Discipline of Histopathology, St. James’ University Hospital, Trinity College Dublin, D08 NHY1 Dublin, Ireland
| | - Elaine Kay
- Department of Pathology, Beaumont University Hospital, D09 V2N0 Dublin, Ireland
| | - Peter Faul
- Department of Pathology, University Hospital Limerick, V94 F858 Limerick, Ireland
| | - Connor O’Keane
- Department of Pathology, Mater University Hospital, D07 R2WY Dublin, Ireland
| | - Roisin O’Connor
- Discipline of Histopathology, St. James’ University Hospital, Trinity College Dublin, D08 NHY1 Dublin, Ireland
| | - Dorinda Mullen
- Discipline of Histopathology, St. James’ University Hospital, Trinity College Dublin, D08 NHY1 Dublin, Ireland
| | - Mataz Nur
- Discipline of Histopathology, St. James’ University Hospital, Trinity College Dublin, D08 NHY1 Dublin, Ireland
| | - Eamon O’Murchu
- National Cancer Registry of Ireland, T12 CDF7 Cork, Ireland
| | - Jacqui Barry-O’Crowley
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
| | - Niamh Kernan
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
| | - Prerna Tewari
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
| | - Helen Keegan
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
| | - Sharon O’Toole
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
- Trinity St James Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland
| | - Robbie Woods
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
| | - Susan Kennedy
- Department of Pathology, St Vincent’s University Hospital, D04 T6F4 Dublin, Ireland
| | - Kenneth Feeley
- Department of Pathology, University Hospital Kerry, V92 NX94 Tralee, Ireland
| | - Linda Sharp
- Faculty of Medical Sciences, Newcastle University, Newcastle NE1 7RU, UK
| | - Tarik Gheit
- Infections and Cancer Biology Laboratory, International Agency for Research on Cancer, 69008 Lyon, France
| | - Massimo Tommasino
- Dipartimento di Farmacia-Scienze del Farmaco, University of Bari, 70121 Bari, Italy
| | - John J. O’Leary
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
- Trinity St James Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland
- Discipline of Histopathology, St. James’ University Hospital, Trinity College Dublin, D08 NHY1 Dublin, Ireland
| | - Cara M. Martin
- TCD CERVIVA Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland
- Trinity St James Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland
- Discipline of Histopathology, St. James’ University Hospital, Trinity College Dublin, D08 NHY1 Dublin, Ireland
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Piludu F, Marzi S, Gangemi E, Farneti A, Marucci L, Venuti A, Benevolo M, Pichi B, Pellini R, Sperati F, Covello R, Sanguineti G, Vidiri A. Multiparametric MRI Evaluation of Oropharyngeal Squamous Cell Carcinoma. A Mono-Institutional Study. J Clin Med 2021; 10:jcm10173865. [PMID: 34501313 PMCID: PMC8432241 DOI: 10.3390/jcm10173865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/10/2021] [Accepted: 08/20/2021] [Indexed: 12/30/2022] Open
Abstract
The aim of this paper is to define the pre-treatment radiological characteristics of oropharyngeal squamous cell carcinoma (OPSCC) using morphological and non-morphological magnetic resonance imaging (MRI), based on HPV status, in a single-institution cohort. In total, 100 patients affected by OPSCC were prospectively enrolled in the present study. All patients underwent 1.5T MR with standard sequences, including diffusion-weighted imaging with and intravoxel incoherent motion (IVIM-DWI) technique and a dynamic contrast-enhanced (DCE) MRI. For all patients, human papillomavirus (HPV) status was available. No statistically significant differences in the volume of primary tumors (PTs) and lymph nodes (LNs) were observed based on HPV status. When comparing the two patient groups, no significant differences were found for the PT radiologic characteristics (presence of well-defined borders, exophytic growth, ulceration, and necrosis) and LN morphology (solid/cystic/necrotic). Tumor subsite, smoking status, and alcohol intake significantly differed based on HPV status, as well as ADC and Dt values of both PTs and LNs. We detected no significant difference in DCE-MRI parameters by HPV status. Based on a multivariate logistic regression model, the combination of clinical factors, such as tumor subsite and alcohol habits, with the perfusion-free diffusion coefficient Dt of LNs, may help to accurately discriminate OPSCC by HPV status.
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Affiliation(s)
- Francesca Piludu
- Department of Radiology and Diagnostic Imaging, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (F.P.); (E.G.)
| | - Simona Marzi
- Medical Physics Laboratory, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy;
| | - Emma Gangemi
- Department of Radiology and Diagnostic Imaging, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (F.P.); (E.G.)
- Center for Integrated Research, Departmental Faculty of Medicine and Surgery, University Campus Bio-Medico of Rome, Via Álvaro del Portillo, 33, 00128 Rome, Italy
| | - Alessia Farneti
- Department of Radiotherapy, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (A.F.); (L.M.); (G.S.)
| | - Laura Marucci
- Department of Radiotherapy, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (A.F.); (L.M.); (G.S.)
| | - Aldo Venuti
- HPV Unit (UOSD), Department of Tumor Immunology and Immunotherapy, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy;
| | - Maria Benevolo
- Department of Pathology, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (M.B.); (R.C.)
| | - Barbara Pichi
- Department of Otolaryngology and Head and Neck Surgery, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (B.P.); (R.P.)
| | - Raul Pellini
- Department of Otolaryngology and Head and Neck Surgery, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (B.P.); (R.P.)
| | - Francesca Sperati
- Biostatistics-Scientific Direction, IRCCS San Gallicano Dermatological Institute, Via Elio Chianesi 53, 00144 Rome, Italy;
| | - Renato Covello
- Department of Pathology, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (M.B.); (R.C.)
| | - Giuseppe Sanguineti
- Department of Radiotherapy, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (A.F.); (L.M.); (G.S.)
| | - Antonello Vidiri
- Department of Radiology and Diagnostic Imaging, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; (F.P.); (E.G.)
- Correspondence: ; Tel.: +39-335-547-6057
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Rezaei M, Karimi Galougahi M, Kheradmand A, Pourabdollah Toutkaboni M, Mir Mohammad Sadeghi H, Abdollahi A, Emami Razavi A, Safavi Naini A, Bidari-Zerehpoosh F. The Frequency of Human Papillomavirus Positivity in Iranian Patients with Head and Neck Squamous Cell Carcinoma. IRANIAN JOURNAL OF PATHOLOGY 2020; 16:20-26. [PMID: 33391376 PMCID: PMC7691708 DOI: 10.30699/ijp.2020.119344.2300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 09/22/2020] [Indexed: 12/24/2022]
Abstract
Background & Objective: Human papillomavirus (HPV) has been associated with prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Similar to the global studies, different prevalence rates of this viral infection have been reported in Iran. Therefore, we aimed to report the prevalence of this virus and its significance in HNSCC patients. Methods: Patients who were referred to the five hospitals of Tehran city from May 2018 to May 2019 were enrolled in this study. All patients were diagnosed with HNSCC based on pathologic study. The pathologic disease staging was defined, and DNAs were extracted from the fresh tissue samples via kits. After polymerase chain reaction (PCR), HPV positive samples were evaluated for determining genotypes and data analysis. Results: Of the 46 patients, three patients (6.5%) showed positive HPV results with the following subtypes: 18 (in two patients), 52 (in three patients), 61 (in two patients), 67, and 73. Comparison of variables between the groups with and without HPV showed a significant difference based on the tumor’s lymphatic invasion (P=0.041), peripheral lymph node involvement (P=0.008), and histologic grade (P=0.011), but no statistically significant difference in terms of other variables such as age, primary tumor site, size, pathologic stage, vascular or perineural invasion, metastasis, smoking, and alcohol consumption was found.
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Affiliation(s)
- Mitra Rezaei
- Virology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahboobeh Karimi Galougahi
- Tracheal Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azin Kheradmand
- Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mihan Pourabdollah Toutkaboni
- Respiratory Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Alireza Abdollahi
- Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirnader Emami Razavi
- Iran National Tumor Bank, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Safavi Naini
- Department of ENT, National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran
| | - Farahnaz Bidari-Zerehpoosh
- Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Kim Y, Joo YH, Kim MS, Lee YS. Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas. J Pathol Transl Med 2020; 54:411-418. [PMID: 32683856 PMCID: PMC7483023 DOI: 10.4132/jptm.2020.06.22] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 06/22/2020] [Indexed: 12/23/2022] Open
Abstract
Background High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites. Methods Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method. Results During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively. Conclusions Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.
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Affiliation(s)
- Yuil Kim
- Department of Hospital Pathology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young-Hoon Joo
- Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min-Sik Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Youn Soo Lee
- Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Costa JM, Sumarroca A, Rodríguez C, Gutiérrez A, García J, López M, Quer M, León X. Prognostic Value of Nodal Involvement in Patients With Oropharyngeal Carcinoma According to the HPV Status. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2020. [DOI: 10.1016/j.otoeng.2019.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Costa JM, Sumarroca A, Rodríguez C, Gutiérrez A, García J, López M, Quer M, León X. Prognostic value of nodal involvement in patients with oropharyngeal carcinoma according to the HPV status. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2020; 71:212-218. [PMID: 31924300 DOI: 10.1016/j.otorri.2019.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Revised: 08/06/2019] [Accepted: 08/13/2019] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND OBJECTIVE Different studies performed in populations with a high incidence of HPV infection have found no prognostic capacity of clinical nodal involvement (cN+) in patients with HPV-positive oropharyngeal carcinomas. The objective of this study was to assess the prognostic ability of nodal involvement in patients with oropharyngeal carcinomas according to HPV status in a cancer population with a low incidence of HPV infection. MATERIAL AND METHODS Retrospective study of a cohort of 420 patients with oropharyngeal carcinomas treated during the period 1990-2016 for whom information on HPV status was available. RESULTS 14.8% of the patients included in the study had HPV-positive tumours. In relation to patients without nodal involvement (cN0), nodal involvement at diagnosis (cN+) significantly decreased the specific survival of patients with HPV-negative oropharyngeal carcinomas. Conversely, no differences in survival were found for patients with HPV-positive tumours according to the presence of nodal involvement. A history of toxic consumption did not change the absence of prognostic significance of nodal involvement for patients with HPV-positive tumours. CONCLUSIONS Regional involvement at the time of diagnosis is not a prognostic variable for patients with HPV-positive oropharyngeal carcinomas.
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Affiliation(s)
- Jose-Miguel Costa
- Servicio de ORL y Cirugía de Cabeza y Cuello, Hospital Moisès Broggi, Sant Joan Despí, Barcelona, España.
| | - Anna Sumarroca
- Servicio de ORL y Cirugía de Cabeza y Cuello, Hospital Moisès Broggi, Sant Joan Despí, Barcelona, España
| | - Camilo Rodríguez
- Servicio de Otorrinolaringología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España
| | - Alfons Gutiérrez
- Servicio de Otorrinolaringología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España
| | - Jacinto García
- Servicio de Otorrinolaringología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España
| | - Montserrat López
- Servicio de Otorrinolaringología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España
| | - Miquel Quer
- Servicio de Otorrinolaringología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España
| | - Xavier León
- Servicio de Otorrinolaringología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, España
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Wang C, Zou H, Yang H, Wang L, Chu H, Jiao J, Wang Y, Chen A. Long non‑coding RNA plasmacytoma variant translocation 1 gene promotes the development of cervical cancer via the NF‑κB pathway. Mol Med Rep 2019; 20:2433-2440. [PMID: 31322217 DOI: 10.3892/mmr.2019.10479] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 05/20/2019] [Indexed: 11/06/2022] Open
Abstract
The long noncoding RNA plasmacytoma variant translocation 1 gene (LncRNA PVT1) has an important role in tumor occurrence and development, yet the role and underlying molecular mechanisms of this RNA in cervical cancer have not yet been elucidated. In the present study, three cervical cancer cell lines (HeLa, Ca Ski and SiHa) were used to verify how LncRNA PVT1 mediates cervical cancer development, and the H8 cell line was used as a control. A LncRNA PVT1 overexpression vector or small interfering RNAs targeting LncRNA PVT1 were transfected into cervical cancer cells to generate LncRNA PVT1 overexpression and silencing in these cells. LncRNA PVT1 overexpression accelerated the growth of cervical cancer cells by advancing the cell cycle and inhibiting cellular apoptosis; increases in Cyclin D1 (CCND1) mRNA and activated Bcl‑2 protein expression levels also supported this finding. Furthermore, NF‑κB activation and expression was increased by LncRNA PVT1 overexpression. In addition, NF‑κB activation or inhibition induced changes in cell viability, accompanied by changes in CCND1 and Bcl‑2 expression. Increases or decreases in microRNA‑16 (miR‑16) expression (using miR mimics and inhibitors) also corresponded to changes in LncRNA PVT1 expression, in vitro. miR‑16 mimics and inhibitor had opposite effects to those of NF‑κB activity, and miR‑16 was demonstrated to directly interact with the NF‑κB gene as measured using the dual‑luciferase assay. In summary, LncRNA PVT1 inhibits the effect of miR‑16, promoting the cell cycle and inhibiting cellular apoptosis of cervical cancer cells, potentially via the NF‑κB pathway. The data from the present study will contribute to the current knowledge surrounding the theoretical basis of cervical cancer and provide a new perspective for the treatment of cervical cancer.
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Affiliation(s)
- Chang Wang
- Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266590, P.R. China
| | - Hao Zou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Hongjuan Yang
- Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266590, P.R. China
| | - Lei Wang
- Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266590, P.R. China
| | - Huijun Chu
- Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266590, P.R. China
| | - Jinwen Jiao
- Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266590, P.R. China
| | - Yankui Wang
- Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266590, P.R. China
| | - Aiping Chen
- Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266590, P.R. China
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9
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Götz C, Bischof C, Wolff KD, Kolk A. Detection of HPV infection in head and neck cancers: Promise and pitfalls in the last ten years: A meta-analysis. Mol Clin Oncol 2019; 10:17-28. [PMID: 30655973 PMCID: PMC6313947 DOI: 10.3892/mco.2018.1749] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 08/09/2018] [Indexed: 12/16/2022] Open
Abstract
The current controversial discussion on the disease-specific survival of patients with human papillomavirus (HPV)-positive (+) and -negative (-) squamous cell carcinoma (SCC) of the head neck region was the motivation for the present meta-analysis. Different detection methods for HPV are available, though these often lack sensitivity. As a consequence, there may be false interpretation of HPV positivity. A bias concerning HPV status and therefore also survival rates is serving a non-durable relevance in the discussion of tailored therapies. A literature search was performed via the online database PubMed/NCBI, and data extraction and statistical analysis were conducted. A total of 139 studies published between 2004 and 2014 were evaluated in the present meta-analysis. The HPV detection methods, patient characteristics, tumor localizations and stages, as well as (neo-) adjuvant therapies and survival times were analyzed. The average incidence rates of HPV+ patients with oropharyngeal tumors were higher than those of patients with cancers of other regions of the head and neck. Upon evaluating the results of different detection methods no significant differences were identified. We have compared the HPV incidence rates of each detection method, when studies have used more than one. Regarding overall survival, the pooled adjusted hazard ratio (HR) for oropharyngeal SCC was 0.31 [95% confidence interval (CI)=0.27-0.36]. Unfortunately, only 3 equivalent studies were available on nonoropharyngeal tumors, for which the pooled adjusted HR was 1 (95% CI=0.73-1.36). Overall, the evaluation demonstrated that the survival rates reported in numerous studies were not evaluated multifactorially and important confounders were excluded from the statistics. The HPV detection methods used were often not sufficient in representing HPV positivity. In addition, oropharyngeal and oral SCCs were assessed together in the localization. The widely differing number of HPV+ patients in each of the various studies may be explained by insufficient detection methods and by a lack of localization distinction. The considerations of a tailored therapy according to HPV status should be rejected based on the present information. The previously published studies should be read critically and do not represent a basis for therapeutic decisions.
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Affiliation(s)
- Carolin Götz
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Clara Bischof
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Klaus-Dietrich Wolff
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Andreas Kolk
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
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Farzal Z, Du E, Yim E, Mazul A, Zevallos JP, Huang BY, Hackman TG. Radiographic muscle invasion not a recurrence predictor in HPV-associated oropharyngeal squamous cell carcinoma. Laryngoscope 2018; 129:871-876. [PMID: 30325502 DOI: 10.1002/lary.27351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 05/16/2018] [Accepted: 05/22/2018] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To determine whether muscle invasion evident on pretreatment imaging in p16 + oropharyngeal squamous cell carcinoma (OPSCC) correlates with recurrence. STUDY DESIGN Retrospective review. METHODS Two-hundred and seventy-six patients with p16 + OPSCC treated at a tertiary referral center from 2003 to 2015 were analyzed. All scans were reviewed by a dedicated neuroradiologist with subspecialty expertise in head and neck imaging. Radiographic evidence of muscle invasion to the genioglossus, hyoglossus, medial pterygoid, and prevertebral muscles was analyzed. Local and regional recurrence rates were compared between the muscle invasion and no muscle invasion groups. RESULTS One hundred and ninety patients met inclusion criteria with adequate follow-up data and pretreatment imaging. Patients were predominantly male (87.5% male) and smokers (65.6% smokers) with a mean age of 56.7 (standard deviation: 9.0 years). Most commonly invaded muscles in the muscle invasion group were hyoglossus (57.8%) and genioglossus (56.3%). There was no statistically significant difference in primary site or nodal recurrence between the combined group, including definite or possible muscle invasion and the group without muscle invasion (P = 0.205 and P = 0.569, respectively). Additionally, no statistically significant difference was present in recurrence-free and disease-specific survival between the two groups at 3- and 5-year follow-up (P > 0.05). CONCLUSION Radiographic evidence of muscle invasion does not appear to be a predictor of human papilloma virus (+) OPSCC recurrence. Additional studies are needed to validate our findings. LEVEL OF EVIDENCE 4 Laryngoscope, 129:871-876, 2019.
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Affiliation(s)
- Zainab Farzal
- Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina
| | - Eugenie Du
- Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina
| | - Eunice Yim
- University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Angela Mazul
- Department of Otolaryngology/Head and Neck Surgery, Washington University, St. Louis, Missouri, U.S.A
| | - Jose P Zevallos
- Department of Otolaryngology/Head and Neck Surgery, Washington University, St. Louis, Missouri, U.S.A
| | - Benjamin Y Huang
- Department of Radiology, University of North Carolina, Chapel Hill, North Carolina
| | - Trevor G Hackman
- Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina
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11
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Faraji F, Padilla ES, Blitz D, Wenderoth MB, Blanco RG, Kawamoto S, Sheth S, Hamper UM, Fakhry C. Reader performance in the ultrasonographic evaluation of oropharyngeal carcinoma. Oral Oncol 2018; 77:105-110. [PMID: 29362115 DOI: 10.1016/j.oraloncology.2017.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Revised: 12/11/2017] [Accepted: 12/20/2017] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To examine reader performance in evaluating oropharyngeal anatomy on ultrasonography. MATERIALS AND METHODS Ultrasound images of the oropharynx comprising normal and malignant anatomic variants were organized into slideshows. Slideshows were administered to 6 readers blinded to participant tumor status and with varying experience reading oropharyngeal sonograms. A training slideshow oriented readers to images of the oropharynx with and without malignant lesions. Readers then evaluated images in a test slideshow for tumor presence and marked orthogonal long and short dimensions of the tumor. Results were analyzed for accuracy, sensitivity, specificity, inter-reader agreement, and measurement error relative to prospectively-identified reference measurements. RESULTS Eighty-seven percent of base of tongue (BOT) sonograms were identified correctly by a majority of readers. In identifying BOT tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 79%, 73%, 85%, and 0.51, respectively. Median measurement error in the long and short axes for BOT tumors was -2.6% (range: -40% to 29%) and -2.6% (range: -56% to 156%), respectively. Eighty-four percent of palatine tonsil sonograms were identified correctly by a majority of readers. In identifying tonsil tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 77%, 74%, 78%, and 0.41, respectively. Median measurement error in the long and short axes for tonsil tumors was 3.8% (range: -45% to 32%) and -6.5% (range: -83% to 42%), respectively. CONCLUSIONS Overall, US has clinically useful sensitivity for identification of oropharyngeal carcinoma among readers of diverse clinical backgrounds and experience. US may be useful for the evaluation of features such as tumor dimensions.
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Affiliation(s)
- Farhoud Faraji
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States.
| | - Ericka S Padilla
- The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, United States.
| | - Dana Blitz
- The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, United States.
| | - Meghan B Wenderoth
- The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, United States.
| | - Ray G Blanco
- Department of Surgery, Greater Baltimore Medical Center, Baltimore, MD, United States.
| | - Satomi Kawamoto
- The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, United States.
| | - Sheila Sheth
- The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, United States.
| | - Ulrike M Hamper
- The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, United States.
| | - Carole Fakhry
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States.
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Amsbaugh MJ, Yusuf M, Cash E, Silverman C, Potts K, Dunlap N. Effect of time to simulation and treatment for patients with oropharyngeal cancer receiving definitive radiotherapy in the era of risk stratification using smoking and human papillomavirus status. Head Neck 2018; 40:687-695. [DOI: 10.1002/hed.24963] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 08/03/2017] [Accepted: 08/16/2017] [Indexed: 11/10/2022] Open
Affiliation(s)
- Mark J. Amsbaugh
- Department of Radiation Oncology; University of Louisville; Louisville Kentucky
| | - Mehran Yusuf
- Department of Radiation Oncology; University of Louisville; Louisville Kentucky
| | - Elizabeth Cash
- Department of Otolaryngology - Head and Neck Surgery and Communicative Disorders; University of Louisville; Louisville Kentucky
| | - Craig Silverman
- Department of Radiation Oncology; University of Louisville; Louisville Kentucky
| | - Kevin Potts
- Department of Otolaryngology - Head and Neck Surgery and Communicative Disorders; University of Louisville; Louisville Kentucky
| | - Neal Dunlap
- Department of Radiation Oncology; University of Louisville; Louisville Kentucky
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Biomarker quantification by multiplexed quantum dot technology for predicting lymph node metastasis and prognosis in head and neck cancer. Oncotarget 2018; 7:44676-44685. [PMID: 27172790 PMCID: PMC5190127 DOI: 10.18632/oncotarget.9225] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 04/22/2016] [Indexed: 01/27/2023] Open
Abstract
Purpose To predict lymph node metastasis and prognosis in head and neck squamous cell carcinoma (HNSCC). Results The combination of membranous E-cadherin and membranous epidermal growth factor receptor (EGFR) quantified by QD technology with age, gender, and grade had greater predictive power than any of the single biomarkers or the two combined biomarkers quantified by conventional immunohistochemistry (IHC). The predictive power of this model was validated in another independent sample set; the predictive sensitivity of this model for LNM was 87.5%, with specificity up to 97.4%, and accuracy 92.9%. Furthermore, a higher membranous E-cadherin level was significantly correlated with better overall and disease-free survival (OS, DFS; P = 0.002, 0.033, respectively), while lower cytoplasmic vimentin and membranous EGFR levels were significantly correlated with better OS (P = 0.016 and 0.021, respectively). The combined biomarkers showed a stronger prognostic value for OS and DFS than any of the single biomarkers. Methods Multiplexed quantum dots (QDs) were used to simultaneously label E-cadherin, vimentin, and EGFR with β-actin as an internal control. Primary tissue samples from 97 HNSCC patients, 49 with and 48 without LNM were included in the training set. Levels of membranous E-cadherin, cytoplasmic vimentin, and membranous EGFR were quantified by InForm software and correlated with clinical characteristics. Conclusions Multiplexed subcellular QD quantification of EGFR and E-cadherin is a potential strategy for the prediction of LNM, DFS, and OS of HNSCC patients.
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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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Epithelial to mesenchymal transition and HPV infection in squamous cell oropharyngeal carcinomas: the papillophar study. Br J Cancer 2017; 116:362-369. [PMID: 28072763 PMCID: PMC5294488 DOI: 10.1038/bjc.2016.434] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 11/25/2016] [Accepted: 12/05/2016] [Indexed: 12/23/2022] Open
Abstract
Background: Human Papillomavirus (HPV) infection is recognised as aetiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPC). HPV-related OPC respond better to treatments and have a significantly favourable outcome. Epithelial to mesenchymal transition (EMT) implicated in tumour invasion, is a hallmark of a poor prognosis in carcinomas. Methods: We have studied the relationship of EMT markers (E-cadherin, β-catenin and vimentin) with HPV infection (DNA and E6/E7 mRNA detection), p16INK4a expression and survival outcomes in a cohort of 296 patients with OPC. Results: Among the 296 OPSSC, 26% were HPV positive, 20.3% had overt EMT (>25% of vimentin positive tumour cells). Lower E-cadherin expression was associated with a higher risk of distant metastasis in univariate (P=0.0110) and multivariate analyses (hazard ratios (HR)=6.86 (1.98; 23.84)). Vimentin expression tends towards worse metastasis-free survival (MFS; HR=2.53 (1.00; 6.41)) and was an independent prognostic factor of progression-free survival (HR=1.55 (1.03; 2.34)). Conclusions: There was a non significant association of EMT with HPV status. This may be explained by a mixed subpopulation of patients HPV positive with associated risk factors (HPV, tobacco and alcohol). Thus, the detection of EMT in OPC represents another reliable approach in the prognosis and the management of OPC whatever their HPV status.
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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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Kawai R, Isomura M, Sato N, Kato S, Yoshida W, Kamiya K, Nagaya Y, Hattori T, Suzuki K, Funato A, Yoshiyama M, Sugita Y, Kubo K, Maeda H. Human Papillomavirus Type 16 Infection and Local Lymph Node Metastasis in Patients with Squamous Cell Carcinoma. J HARD TISSUE BIOL 2016. [DOI: 10.2485/jhtb.25.115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Ryoko Kawai
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Madoka Isomura
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Nobuaki Sato
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Seeta Kato
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
- Research Institute of Advanced Oral Science, Graduate School of Dentistry, Aichi Gakuin University
| | - Waka Yoshida
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
- Research Institute of Advanced Oral Science, Graduate School of Dentistry, Aichi Gakuin University
| | - Kei Kamiya
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Yoshitaka Nagaya
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Tomofumi Hattori
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Koji Suzuki
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Akiyoshi Funato
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Masanori Yoshiyama
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
| | - Yoshihiko Sugita
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
- Research Institute of Advanced Oral Science, Graduate School of Dentistry, Aichi Gakuin University
| | - Katsutoshi Kubo
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
- Research Institute of Advanced Oral Science, Graduate School of Dentistry, Aichi Gakuin University
| | - Hatsuhiko Maeda
- Department of Oral Pathology, School of Dentistry, Aichi Gakuin University
- Research Institute of Advanced Oral Science, Graduate School of Dentistry, Aichi Gakuin University
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Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell carcinomas indicate HPV status? Clin Nucl Med 2015; 40:e196-200. [PMID: 25608156 DOI: 10.1097/rlu.0000000000000691] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVE The aim of this study was to explore the relationship of PET/CT parameters with human papillomavirus (HPV) status of oropharyngeal (OP) and oral cavity (OC) squamous cell carcinomas (SCCs). PATIENTS AND METHODS We retrospectively reviewed 39 patients with OC and OP-SCC who underwent staging 18F-FDG PET/CT. PET/CT parameters were measured for the primary tumor and the hottest involved node, including SUV max, SUV mean, SUV peak, metabolic tumor volume, total lesion glycolysis, standardized added metabolic activity (SAM), and normalized SAM. Patient characteristics were compared between HPV positive (HPV+) and negative (HPV-) groups. Receiver operating characteristic analysis was used to dichotomize PET/CT parameters into high and low. Logistic regression models predicting HPV status were fit for each PET/CT parameter. RESULTS The HPV+ group was composed of 18 patients all with OP-SCC; the HPV- group consisted of 21 patients, 4 OP cancer patients and 17 OC cancer patients. The HPV+ group had a higher proportion of N2 stage (94% vs 43%; P < 0.001). Nodal PET/CT parameters were higher in the HPV+ group (P < 0.01); this difference was not present for the primary lesion. After adjusting for sex and age, the association of higher nodal SUV max (odds ratio [OR], 9.67), SUV mean (OR, 10.48), SUV peak (OR 9.67), metabolic tumor volume (OR, 14.52), total lesion glycolysis (OR, 11.84), and SAM, normalized SAM (OR, 16.21) with HPV+ status remained statistically significant (P < 0.05). CONCLUSIONS Nodal PET/CT parameters predict HPV status. High nodal FDG uptake should raise suspicion for positive HPV status in the evaluation of the primary lesion.
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Wang MB, Liu IY, Gornbein JA, Nguyen CT. HPV-Positive Oropharyngeal Carcinoma. Otolaryngol Head Neck Surg 2015; 153:758-69. [DOI: 10.1177/0194599815592157] [Citation(s) in RCA: 92] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Accepted: 05/29/2015] [Indexed: 10/23/2022]
Abstract
Objective Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma is increasing in incidence and appears to exhibit improved response to treatment and better survival than that of HPV– head and neck squamous cell carcinoma. The purpose of this systematic review was to examine the current literature regarding treatment and prognosis of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) and identify whether type of treatment (primarily surgery vs primarily radiation) significantly affects survival rates. Data Sources PubMed and Cochrane Library databases. Review Methods A computerized search of the PubMed and Cochrane Library databases was performed to identify English-language articles published between January 1, 2000, and October 21, 2014. Studies were included only if they were prospective or retrospective observational series of OPSCC patients that reported HPV status, treatment regimen, and survival outcomes. Outcomes were determined for HPV+ and HPV– OPSCC patients, with subanalyses according to the type of treatment received. Results Fifty-six articles were eligible for this review. In the HPV+ analysis, the unadjusted hazard rate ratio (HR) for surgery vs radiation treatment was 1.33 ( P = .114). Nine confounders were considered, and HRs were adjusted for each covariate. While HRs were almost all >1 for all covariates, none of the HRs was statistically significant at P < .05. The HR for HPV– OPSCC was higher for radiation than surgery. Conclusions HPV+ OPSCC has an improved prognosis and lower rates of adverse events when compared with HPV– OPSCC. HPV– OPSCC had significantly worse outcomes when treated with primary radiation as compared with primary surgery. There was no statistically significant difference in HRs for HPV+ OPSCC with primary radiation vs primary surgery treatment.
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Affiliation(s)
- Marilene B. Wang
- Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA
| | - Isabelle Y. Liu
- Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA
| | - Jeffrey A. Gornbein
- Statistical/Biomathematical Consulting Clinic, Department of Biomathematics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA
| | - Chau T. Nguyen
- Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA
- Anacapa Surgical Associates, Ventura, California, USA
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Saito Y, Yoshida M, Omura G, Kobayashi K, Fujimoto C, Ando M, Sakamoto T, Asakage T, Yamasoba T. Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma. Jpn J Clin Oncol 2015; 45:828-36. [DOI: 10.1093/jjco/hyv085] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2014] [Accepted: 05/08/2015] [Indexed: 12/13/2022] Open
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Steinestel J, Al Ghazal A, Arndt A, Schnoeller TJ, Schrader AJ, Moeller P, Steinestel K. The role of histologic subtype, p16(INK4a) expression, and presence of human papillomavirus DNA in penile squamous cell carcinoma. BMC Cancer 2015; 15:220. [PMID: 25885064 PMCID: PMC4392470 DOI: 10.1186/s12885-015-1268-z] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2014] [Accepted: 03/25/2015] [Indexed: 12/22/2022] Open
Abstract
Background Up to 50% of penile squamous cell carcinomas (pSCC) develop in the context of high-risk human papillomavirus (HR-HPV) infection. Most of these tumours have been reported to show basaloid differentiation and overexpression of tumour suppressor protein p16INK4a. Whether HPV-triggered carcinogenesis in pSCC has an impact on tumour aggressiveness, however, is still subject to research. Methods In tissue specimens from 58 patients with surgically treated pSCC between 1995 and 2012, we performed p16INK4a immunohistochemistry and DNA extraction followed by HPV subtyping using a PCR-based approach. The results were correlated with histopathological and clinical parameters. Results 90.4% of tumours were of conventional (keratinizing) subtype. HR-HPV DNA was detected in 29.3%, and a variety of p16INK4a staining patterns was observed in 58.6% of samples regardless of histologic subtype. Sensitivity of basaloid subtype to predict HR-HPV positivity was poor (11.8%). In contrast, sensitivity and specificity of p16INK4a staining to predict presence of HR-HPV DNA was 100% and 57%, respectively. By focussing on those samples with intense nuclear staining pattern for p16INK4a, specificity could be improved to 83%. Both expression of p16INK4a and presence of HR-HPV DNA, but not histologic grade, were inversely associated with pSCC tumour invasion (p = 0.01, p = 0.03, and p = 0.71). However, none of these correlated with nodal involvement or distant metastasis. In contrast to pathological tumour stage, the HR-HPV status, histologic grade, and p16INK4a positivity failed to predict cancer-specific survival. Conclusions Our results confirm intense nuclear positivity for p16INK4a, rather than histologic subtype, as a good predictor for presence of HR-HPV DNA in pSCC. HR-HPV / p16INK4a positivity, independent of histological tumour grade, indicates a less aggressive local behaviour; however, its value as an independent prognostic indicator remains to be determined. Since local invasion can be judged without p16INK4a/HPV-detection on microscopic evaluation, our study argues against routine testing in the setting of pSCC.
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Affiliation(s)
- Julie Steinestel
- Department of Urology, Muenster University Medical Center, Albert-Schweitzer-Campus 1, A1, 48149, Muenster, Germany.
| | - Andreas Al Ghazal
- Department of Urology, University of Ulm, Prittwitzstrasse 43, 89075, Ulm, Germany.
| | - Annette Arndt
- Institute of Pathology and Molecular Pathology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany.
| | - Thomas J Schnoeller
- Department of Urology, University of Ulm, Prittwitzstrasse 43, 89075, Ulm, Germany.
| | - Andres J Schrader
- Department of Urology, Muenster University Medical Center, Albert-Schweitzer-Campus 1, A1, 48149, Muenster, Germany.
| | - Peter Moeller
- Institute of Pathology, University of Ulm, Albert-Einstein-Allee 23, 89070, Ulm, Germany.
| | - Konrad Steinestel
- Gerhard Domagk Institute of Pathology, University of Muenster, Domagkstrasse 17, 48149, Muenster, Germany.
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Joo YH, Yoo IR, Lee YS, Cho KJ, Park JO, Nam IC, Kim CS, Kim SY, Kim MS. Association between the standardized uptake value and high-risk HPV in hypopharyngeal squamous cell carcinoma. Acta Otolaryngol 2014; 134:1062-70. [PMID: 25220728 DOI: 10.3109/00016489.2014.905701] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONCLUSION Median (18)F-FDG PET/CT maximum standardized uptake values (SUV max) cut-off values of 7.9 or greater were associated with high-risk human papillomavirus (HPV) negativity in patients with hypopharyngeal squamous cell carcinoma (HPSCC). Furthermore, median (18)F-FDG PET/CT SUV max cut-off values of 7.9 or greater and high-risk HPV negativity were associated with adverse outcomes. OBJECTIVES We studied the association and the potential prognostic significance of (18)F-FDG PET/CT and high-risk HPV status in HPSCC. METHODS The medical records of 45 patients who underwent (18)F-FDG PET/CT for HPSCC before surgery were reviewed. High-risk HPV in situ hybridization was performed to detect HPV infection. RESULTS The median SUV max was 9.91 ± 4.91 (range 1.9-22.1) and the positive rate of high-risk HPV in situ hybridization was 11% (5 of 45). The SUV max values of negativity for the high-risk HPV subtypes (10.47 ± 4.87) and positivity (5.48 ± 2.45) were found to be significantly different (p = 0.030). The SUV max cut-off value for differentiating negativity for the high-risk HPV subtypes from positivity was 7.9, with a sensitivity of 65% and a specificity of 80%. The 5-year disease-specific survival rate (DSSR) in our cohort was 57%. Patients with an SUV max value higher than 7.9 (p = 0.005) and high-risk HPV negativity (p = 0.047) had decreased 5-year DSSR.
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Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via PI3K/Akt pathway. Tumour Biol 2014; 35:11261-7. [PMID: 25113250 DOI: 10.1007/s13277-014-2337-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 07/09/2014] [Indexed: 01/08/2023] Open
Abstract
Cervical cancer (CC) is a malignant neoplasm arising from cells originating in the cervix uteri, among the top causes of death from cancer in women. In a gene expression profiling study of metabolic response to treatment, PI3K/Akt signaling pathway are associated with the development of CC. A common mechanism of Akt activation seen in cancer types is alterations in the upstream regulators of Akt such as phosphatidylinositol 3-kinase (PI3K), which is overexpressed in cervical cancer tissues, and leads to phosphorylation of Akt. Both PI3K and Akt inhibitors exist and may be therapeutically valuable. In the present study, we use MTT assay and western blot for the high-throughput screening to select specific inhibitors of PI3K/Akt signaling pathway, and then obtain fucoxanthin. Fucoxanthin is a water-soluble dietary fiber, taken from the unique slimy component of alginic cells. Various studies have pointed out that fucoxanthin is very effective for the treatment of cancer. Our results have shown that fucoxanthin induced a significant apoptosis of HeLa cells, compared with other candidates. After treatment with fucoxanthin for 24 h, the level of phosphorylation was inhibited in a dose-dependent manner, and the proteins of apoptotic markers were changed in HeLa cells. And fucoxanthin could suppress tumor growth in vivo. In addition, the mitochondrial signal transduction pathway maybe was involved in its mechanism and NF-κB activation was decreased after treatment with fucoxanthin. Therefore, fucoxanthin may be used as anti-cervical cancer drugs in the future.
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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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25
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Joo YH, Cho KJ, Park JO, Nam IC, Kim CS, Kim MS. High-risk human papillomavirus and lymph node size in patients with single node metastasis of oral and oropharyngeal cancer. Acta Otolaryngol 2014; 134:395-400. [PMID: 24628336 DOI: 10.3109/00016489.2013.844364] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONCLUSION High-risk human papillomavirus (HPV) infection was significantly related to lymph node size in patients with single node metastasis of oral and oropharyngeal cancer. OBJECTIVE The purpose of this study was to examine the relationship between high-risk HPV infection and lymph node size in patients with single node metastasis of oral and oropharyngeal carcinoma. METHODS This study included 48 patients with oral and oropharyngeal carcinoma. Pathologic lymph node stages comprised 36 N1 and 12 N2a. RESULTS High-risk HPV in situ hybridization was positive in 29% of patients (14/48). Of those patients with high-risk HPV, there was a significant difference (p = 0.008) between oral (9.5%) and oropharyngeal (44.4%) cancers. Average lymph node diameter was 20.7 ± 12.6 mm (range 5-54 mm). We found a positive correlation between high-risk HPV status and lymph node size (p = 0.018). Mean lymph node diameter in high-risk HPV-positive cases was 27.3 ± 13.1 mm and 18.0 ± 11.5 mm in high-risk HPV-negative cases. Extracapsular spread (p = 0.030) and cystic nodal metastases (p = 0.019) were also significantly related to lymph node size. High-risk HPV negative status (p = 0.043), advanced tumor stage (p = 0.009), and extracapsular spread (p = 0.038) all had significant adverse effects on 5-year disease-specific survival.
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Affiliation(s)
- Young-Hoon Joo
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Catholic University of Korea , Seoul , Republic of Korea
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Maier M, Kraft K, Steinestel K, Schramm A, Lorenz KJ, Tisch M, Schwerer M, Maier H. [Human papillomavirus in squamous cell cancer of the head and neck. A study at the Ulm Military Hospital, Germany]. HNO 2014; 61:593-601. [PMID: 23842698 DOI: 10.1007/s00106-013-2676-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
There is increasing evidence worldwide that human papillomavirus is a major risk factor for head and neck cancer. Only few studies on this association have been performed in Germany to date. For the purposes of the present study, tumor specimens from 223 patients with squamous cell cancer of the oral cavity, oropharynx, hypopharynx and larynx were analyzed for HPV DNA and p16INK4a expression. The prevalence of HPV genotype 16 (HPV16) DNA in the study population was 17.5%. Further high-risk HPV types were not detected. All HPV16-positive tumors showed intense p16INK4a expression. HPV16 prevalence was highest in tonsillar carcinoma (37.5%) and lowest in laryngeal cancer (2.8%). We observed a significantly higher incidence of cervical lymph node metastases in patients with HPV16-positive tonsillar carcinoma in comparison to HPV-negative tumors (p < 0.016). Tobacco and/or alcohol consumption was significantly lower in patients with HPV-positive tumors (p < 0.0001).
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Affiliation(s)
- M Maier
- Univ.-HNO-Klinik Heidelberg.
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Hirshoren N, Bulvik R, Neuman T, Rubinstein AM, Meirovitz A, Elkin M. Induction of heparanase by HPV E6 oncogene in head and neck squamous cell carcinoma. J Cell Mol Med 2013; 18:181-6. [PMID: 24286246 PMCID: PMC3916129 DOI: 10.1111/jcmm.12179] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 10/07/2013] [Indexed: 12/11/2022] Open
Abstract
High-risk human papillomavirus (HPV)-positive head and neck squamous cell carcinomas (HNSCCs) are highly invasive; however the identity of downstream effectors responsible for their aggressive phenotype remains underinvestigated. Here, we report that HPV-mediated up-regulation of heparanase enzyme can provide mechanistic explanation for augmented invasiveness of HPV-positive HNSCCs. Heparanase is the sole mammalian enzyme (endo-β-d-glucuronidase) degrading heparan sulphate glycosaminoglycan, key polysaccharide of the extracellular matrix. Cleavage of heparan sulphate by heparanase leads to disassembly of extracellular barriers, enabling local invasion and metastatic spread of the tumour, and releases heparan sulphate-bound growth factors from the extracellular depots. Heparanase is tightly implicated in head and neck cancer progression; yet, molecular mechanisms underlying transcriptional activation of the heparanase gene in HNSCC are largely unknown. We found that HPV16 oncogene E6 is capable of inducing overexpression of heparanase in HNSCC. Notably, radiation treatment dose-dependently suppresses E6-induced heparanase expression in vitro. Our results provide the first evidence for a functional involvement of HPV in heparanase induction in head and neck tumourigenesis and, given ongoing clinical testing of several heparanase-inhibiting compounds, offer important avenue for future therapeutic exploration in HNSCC, as well as other HPV-associated malignancies (i.e. cervical carcinoma).
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Affiliation(s)
- Nir Hirshoren
- Department of Otolaryngology, Head & Neck Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
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García-de Marcos JA, Pérez-Zafrilla B, Arriaga Á, Arroyo-Rodríguez S, Poblet E. Human papillomavirus in carcinomas of the tongue: clinical and prognostic implications. Int J Oral Maxillofac Surg 2013; 43:274-80. [PMID: 24268899 DOI: 10.1016/j.ijom.2013.10.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Revised: 08/31/2013] [Accepted: 10/16/2013] [Indexed: 11/18/2022]
Abstract
It is not clear whether the presence of human papillomavirus (HPV) in squamous cell carcinomas of the tongue (SCCT) is of etiopathogenic and clinical significance. This study was designed to establish the incidence of HPV in SCCT and to determine the influence of HPV detection on clinical parameters and the prognosis. Clinical and histopathological data of 64 patients with SCCT were collected. Thirty benign lesions of the tongue were analyzed in parallel, in order to compare the HPV incidence and genotypes in these lesions with those of SCCT. Paraffin blocks of all cases were collected and PCR was carried out using SPF10 primers and the INNO-LiPA genotyping methodology. HPV was detected in 26.2% of the patients. Hybridization results showed that all patients except one had high-risk (HR)-HPV. HPV56 was the most common (42.1%), followed by HPV18 (26.3%), HPV16 (10.5%), HPV66 (10.5%), HPV39 (5.3%), and HPV51 (5.3%). The odds ratio of HR-HPV infection in cases vs. controls was statistically significant (9.45, 95% confidence interval 1.18-75.46). Among the results of the univariate analysis correlating the presence of HR-HPV with different clinical parameters, only mortality showed a statistically significant correlation, being higher in HR-HPV patients (odds ratio 3.97, 95% confidence interval 1.07-14.7).
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Affiliation(s)
- J-A García-de Marcos
- Department of Oral and Maxillofacial Surgery, Albacete University Hospital, Albacete, Spain.
| | - B Pérez-Zafrilla
- Department of Oral and Maxillofacial Surgery, Albacete University Hospital, Albacete, Spain
| | - Á Arriaga
- Department of Oral and Maxillofacial Surgery, Albacete University Hospital, Albacete, Spain
| | - S Arroyo-Rodríguez
- Department of Oral and Maxillofacial Surgery, Albacete University Hospital, Albacete, Spain
| | - E Poblet
- Department of Oral and Maxillofacial Surgery, Albacete University Hospital, Albacete, Spain
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Joo YH, Lee YS, Cho KJ, Park JO, Nam IC, Kim CS, Kim SY, Kim MS. Characteristics and prognostic implications of high-risk HPV-associated hypopharyngeal cancers. PLoS One 2013; 8:e78718. [PMID: 24244346 PMCID: PMC3823884 DOI: 10.1371/journal.pone.0078718] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Accepted: 09/18/2013] [Indexed: 12/01/2022] Open
Abstract
Background High-risk human papillomavirus (HPV) is an oncogenic virus that causes oropharyngeal cancers, and it has a favorable outcome after the treatment. Unlike in oropharyngeal cancer, the prevalence and role of high-risk HPV in the etiology of hypopharyngeal squamous cell carcinoma (HPSCC) is uncertain. Objective The aim of the present study was to evaluate the effect and prognostic significance of high-risk HPV in patients with HPSCC. Methods The study included 64 subjects with HPSCC who underwent radical surgery with or without radiation-based adjuvant therapy. Primary tumor sites were the pyriform sinus in 42 patients, posterior pharyngeal wall in 19 patients, and postcricoid area in 3 patients. High-risk HPV in situ hybridization was performed to detect HPV infection. Results The positive rate of high-risk HPV in situ hybridization was 10.9% (7/64). There was a significant difference in the fraction of positive high-risk HPV among pyriform sinus cancer (16.7%), posterior pharyngeal wall cancer (0%), and postcricoid area cancer (0%) (p = 0.042). The laryngoscopic examination revealed a granulomatous and exophytic appearance in 85.7% (6/7) of patients with high-risk HPV-positive pyriform sinus cancer, but in only 31.4% (11/35) of patients with high-risk HPV-negative pyriform sinus cancer (p = 0.012). Significant correlations were found between positive high-risk HPV and younger age (p = 0.050) and non-smoking status (p = 0.017). HPV-positive patients had a significantly better disease-free survival (p = 0.026) and disease-specific survival (p = 0.047) than HPV-negative patients. Conclusions High-risk HPV infection is significantly related to pyriform sinus cancer in patients with HPSCC.
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Affiliation(s)
- Young-Hoon Joo
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Youn-Soo Lee
- Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kwang-Jae Cho
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jun-Ook Park
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - In-Chul Nam
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chung-Soo Kim
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sang-Yeon Kim
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min-Sik Kim
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
- * E-mail:
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Yang Z, Deng R, Sun G, Huang X, Tang E. Cervical metastases from squamous cell carcinoma of hard palate and maxillary alveolus: A retrospective study of 10 years. Head Neck 2013; 36:969-75. [PMID: 23733304 DOI: 10.1002/hed.23398] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Revised: 01/05/2013] [Accepted: 05/23/2013] [Indexed: 12/27/2022] Open
Affiliation(s)
- Zinan Yang
- Department of Oral and Maxillofacial Surgery; Stomatological Hospital Affiliated Medical School; Nanjing University; Nanjing Jiangsu province People's Republic of China
- Department of Oral and Maxillofacial Surgery; Hospital of Stomatology, Guangzhou Medical University; Guangzhou Guangdong province People's Republic of China
| | - Runzhi Deng
- Department of Oral and Maxillofacial Surgery; Stomatological Hospital Affiliated Medical School; Nanjing University; Nanjing Jiangsu province People's Republic of China
| | - Guowen Sun
- Department of Oral and Maxillofacial Surgery; Stomatological Hospital Affiliated Medical School; Nanjing University; Nanjing Jiangsu province People's Republic of China
| | - Xiaofeng Huang
- Department of Oral and Maxillofacial Surgery; Stomatological Hospital Affiliated Medical School; Nanjing University; Nanjing Jiangsu province People's Republic of China
| | - Enyi Tang
- Department of Oral and Maxillofacial Surgery; Stomatological Hospital Affiliated Medical School; Nanjing University; Nanjing Jiangsu province People's Republic of China
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An analysis of the epidemiological and etiological factors of oral tumors of young adults in a Central-Eastern European population. Pathol Oncol Res 2013; 19:353-63. [PMID: 23645516 DOI: 10.1007/s12253-013-9628-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Accepted: 03/18/2013] [Indexed: 01/27/2023]
Abstract
The etiology of tumors in young age is not precisely known yet, but studies on the topic generally agree that in this group of patients the traditionally known behavioural risk factors (tobacco and alcohol abuse) play no or a significantly less important role. Oral squamous cell carcinoma occurring at a young age is a topic of utmost importance that is extensively and intensively researched as, while the overall incidence of oral cancer is decreasing worldwide, that of squamous cell carcinoma diagnosed in young adults is steadily increasing. The present article aims at presenting the main questions and characteristics of tumors in young adults in Central-Eastern Europe and in developed West European countries as contrasted to tumors found in middle aged and elderly patients. Factors influencing the development of oral cancer include regulatory factors of the cell cycle, the inherited vulnerability of the genetic code of certain proteins and the presence of HPV infection with an oncogenic genotype. The connections of HPV infection and genetic damages are studied intensively. It is known that the prevalence of oral HPV infections is growing with a background of potentially changing sexual habits. It is debated, however, whether smoking and alcohol consumption could have a connection to HPV associated oral cancer and whether the spread of HPV in itself could be an explanation for the growing occurrence of young-age tumors. There is no consensus in the literature as to the prognostic significance of age. Some research groups have found a better life expectancy for young patients, while other authors found a worse prognosis for these patients. It is known that the prognosis of head and neck tumors, the prevalence of HPV infections as well as genetic mutations show regional and ethnic variations. This might be explained by differences in the degree of development of a preventive system, in the quality of care and in the attitudes of young patients towards visiting a doctor. The study is made difficult by incomparable patient selection criteria as well as by the question of the intraoral localisation of tumors as an independent risk factor.
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Teymoortash A, Werner JA. Current advances in diagnosis and surgical treatment of lymph node metastasis in head and neck cancer. GMS CURRENT TOPICS IN OTORHINOLARYNGOLOGY, HEAD AND NECK SURGERY 2012; 11:Doc04. [PMID: 23320056 PMCID: PMC3544246 DOI: 10.3205/cto000086] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Still today, the status of the cervical lymph nodes is the most important prognostic factor for head and neck cancer. So the individual treatment concept of the lymphatic drainage depends on the treatment of the primary tumor as well as on the presence or absence of suspect lymph nodes in the imaging diagnosis. Neck dissection may have either a therapeutic objective or a diagnostic one. The selective neck dissection is currently the method of choice for the treatment of patients with advanced head and neck cancers and clinical N0 neck. For oncologic reasons, this procedure is generally recommended with acceptable functional and aesthetic results, especially under the aspect of the mentioned staging procedure. In this review article, current aspects on pre- and posttherapeutic staging of the cervical lymph nodes are described and the indication and the necessary extent of neck dissection for head and neck cancer is discussed. Additionally the critical question is discussed if the lymph node metastasis bears an intrinsic risk of metastatic development and thus its removal in a most possible early stage plays an important role.
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Affiliation(s)
- A. Teymoortash
- Department of Otolaryngology, Head & Neck Surgery, University of
Marburg, Germany
| | - J. A. Werner
- Department of Otolaryngology, Head & Neck Surgery, University of
Marburg, Germany
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Haughey BH, Sinha P. Prognostic factors and survival unique to surgically treated p16+ oropharyngeal cancer. Laryngoscope 2012; 122 Suppl 2:S13-33. [DOI: 10.1002/lary.23493] [Citation(s) in RCA: 123] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Lee LA, Huang CG, Liao CT, Lee LY, Hsueh C, Chen TC, Lin CY, Fan KH, Wang HM, Huang SF, Chen IH, Kang CJ, Ng SH, Yang SL, Tsao KC, Chang YL, Yen TC. Human papillomavirus-16 infection in advanced oral cavity cancer patients is related to an increased risk of distant metastases and poor survival. PLoS One 2012; 7:e40767. [PMID: 22808258 PMCID: PMC3395633 DOI: 10.1371/journal.pone.0040767] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2012] [Accepted: 06/13/2012] [Indexed: 11/25/2022] Open
Abstract
Background Human papillomavirus (HPV) is an oncogenic virus causing oropharyngeal cancers and resulting in a favorable outcome after the treatment. The role of HPV in oral cavity squamous cell carcinoma (OSCC) remains ambiguous. Objective This study aimed to examine the effect of HPV infection on disease control among patients with OSCC following radical surgery with radiation-based adjuvant therapy. Patients and Method We prospectively followed 173 patients with advanced OSCC (96% were stage III/IV) who had undergone radical surgery and adjuvant therapy between 2004 and 2006. They were followed between surgery and death or up to 60 months. Surgical specimens were examined using a PCR-based HPV blot test. The primary endpoints were the risk of relapse and the time to relapse; the secondary endpoints were disease-free survival, disease-specific survival, and overall survival. Results The prevalence of HPV-positive OSCC was 22%; HPV-16 (9%) and HPV-18 (7%) were the genotypes most commonly encountered. Solitary HPV-16 infection was a poor predictor of 5-year distant metastases (hazard ratio, 3.4; 95% confidence interval, 1.4–8.0; P = 0.005), disease-free survival (P = 0.037), disease-specific survival (P = 0.006), and overall survival (P = 0.010), whereas HPV-18 infection had no impact on 5-year outcomes. The rate of 5-year distant metastases was significantly higher in the HPV-16 or level IV/V metastasis group compared with both the extracapsular spread or tumor depth ≥11-mm group and patients without risk factors (P<0.001). Conclusions HPV infections in advanced OSCC patients are not uncommon and clinically relevant. Compared with HPV-16-negative advanced OSCC patients, those with a single HPV-16 infection are at higher risk of distant metastases and poor survival despite undergoing radiation-based adjuvant therapy and require a more aggressive adjuvant treatment and a more thorough follow-up.
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Affiliation(s)
- Li-Ang Lee
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Chung-Guei Huang
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Chun-Ta Liao
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- * E-mail: (TCY); (CTL)
| | - Li-Yu Lee
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Chuen Hsueh
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Tse-Ching Chen
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Chien-Yu Lin
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Kang-Hsing Fan
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Hung-Ming Wang
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Medical Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Shiang-Fu Huang
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - I-How Chen
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Chung-Jan Kang
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Shu-Hang Ng
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Diagnostic Radiology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Shu-Li Yang
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Laboratory Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Kuo-Chien Tsao
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Laboratory Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Yu-Liang Chang
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Oral and Maxillofacial Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Tzu-Chen Yen
- Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
- * E-mail: (TCY); (CTL)
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Liu Y, Xie S, Wang Y, Luo K, Wang Y, Cai Y. Liquiritigenin inhibits tumor growth and vascularization in a mouse model of HeLa cells. Molecules 2012; 17:7206-16. [PMID: 22692244 PMCID: PMC6268641 DOI: 10.3390/molecules17067206] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2012] [Revised: 06/01/2012] [Accepted: 06/07/2012] [Indexed: 12/28/2022] Open
Abstract
Angiogenesis is one of the crucial steps in the transition of a tumor from a small, harmless cluster of mutated cells to a large, malignant growth, capable of spreading to other organs throughout the body. Vascular endothelial growth factor (VEGF) that stimulates vasculogenesis and angiogenesis is thought to be as an anti-angiogenic target for cancer therapy. Liquiritigenin (LQ), a flavanone existing in Radix glycyrrhiza, shows extensive biological activities, such as anti-inflammatory and anti-cancer properties. In our studies, liquiritigenin effectively inhibited the growth of tumors xenografted in nude mice from human cervical cancer cell line HeLa cells, and microvascular density (MVD) of the tumor exposed to liquiritigenin was reduced in a dose dependent manner, especially in the high dose group. Moreover, the expression and secretion of VEGF were down-regulated by the drug in vivo and in vitro. Therefore, liquiritigenin can be further studied on cancer and other diseases associated with VEGF up-regulation.
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Affiliation(s)
| | | | | | | | | | - Yunqing Cai
- Author to whom correspondence should be addressed; ; Tel.: +86-25-8666-2941; Fax: +86-25-8666-2930
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Joseph AW, D'Souza G. Epidemiology of human papillomavirus-related head and neck cancer. Otolaryngol Clin North Am 2012; 45:739-64. [PMID: 22793850 DOI: 10.1016/j.otc.2012.04.003] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Human papillomavirus (HPV) is now recognized to cause a subset of head and neck squamous cell carcinomas (HNSCC). Although excessive tobacco and alcohol use continue to be important risk factors for HNSCC, epidemiologic studies suggest that more than 25% of HNSCC are now caused by HPV. The incidence of HPV-related HNSCC is increasing, highlighting the need to understand the oral HPV infections causing these cancers. This article reviews the evidence for a causal association between HPV and HNSCC, examines the changing epidemiologic trends of HNSCC, and discusses what is currently known about oral HPV infection, natural history, and transmission.
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Affiliation(s)
- Andrew W Joseph
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, JHOC 6th Floor, 601 North Caroline Street, Baltimore, MD 21287, USA
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Virology and molecular pathogenesis of HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma. Biochem J 2012; 443:339-53. [PMID: 22452816 DOI: 10.1042/bj20112017] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The current literature fully supports HPV (human papillomavirus)-associated OPSCC (oropharyngeal squamous cell carcinoma) as a unique clinical entity. It affects an unambiguous patient population with defined risk factors, has a genetic expression pattern more similar to cervical squamous cell carcinoma than non-HPV-associated HNSCC (head and neck squamous cell carcinoma), and may warrant divergent clinical management compared with HNSCC associated with traditional risk factors. However, a detailed understanding of the molecular mechanisms driving these differences and the ability to exploit this knowledge to improve clinical management of OPSCC has not yet come to fruition. The present review summarizes the aetiology of HPV-positive (HPV+) OPSCC and provides a detailed overview of HPV virology and molecular pathogenesis relevant to infection of oropharyngeal tissues. Methods of detection and differential gene expression analyses are also summarized. Future research into mechanisms that mediate tropism of HPV to oropharyngeal tissues, improved detection strategies and the pathophysiological significance of altered gene and microRNA expression profiles is warranted.
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