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Sheikh M, Roshandel G, McCormack V, Malekzadeh R. Current Status and Future Prospects for Esophageal Cancer. Cancers (Basel) 2023; 15:765. [PMID: 36765722 PMCID: PMC9913274 DOI: 10.3390/cancers15030765] [Citation(s) in RCA: 92] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 01/10/2023] [Accepted: 01/20/2023] [Indexed: 01/28/2023] Open
Abstract
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes.
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Affiliation(s)
- Mahdi Sheikh
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
| | - Valerie McCormack
- Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 14117-13135, Iran
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The 8th Wonder of the Cancer World: Esophageal Cancer and Inflammation. Diseases 2022; 10:diseases10030044. [PMID: 35892738 PMCID: PMC9326664 DOI: 10.3390/diseases10030044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/22/2022] [Accepted: 07/04/2022] [Indexed: 11/17/2022] Open
Abstract
Esophageal cancer is a devastating malignancy which can be detected at an early stage but is more often diagnosed as an advanced process. It affects both men and women and inflicts the young and the elderly. There are multiple underlying factors involved in the pathogenesis of this cancer including inflammation. The interplay of these factors promotes inflammation through various mechanisms including the recruitment of pro-inflammatory cells, mediators such as cytokines, reactive oxygen species, and interleukins, among others. The presentation can vary widely with one of the most notable symptoms being dysphagia. Diagnosis is based on clinical symptomatology, imaging and endoscopy with biopsy. Once the diagnosis has been established, treatment and prognosis are based on the stage of the disease. This review outlines esophageal cancer and its link to inflammation in relation to pathogenesis, along with clinical features, diagnosis and treatment.
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Lin CC, Doi T, Muro K, Hou MM, Esaki T, Hara H, Chung HC, Helwig C, Dussault I, Osada M, Kondo S. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort in Asia. Target Oncol 2021; 16:447-459. [PMID: 33840050 PMCID: PMC8266718 DOI: 10.1007/s11523-021-00810-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Patients with esophageal squamous cell carcinoma (SCC) have limited treatment options. Blocking transforming growth factor-β (TGFβ), which can be overexpressed in these tumors, may enhance responses to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGFβ receptor II (TGFβRII) (a TGFβ "trap") fused to a human IgG1 monoclonal antibody blocking PD-L1. OBJECTIVE The objective of this study was to investigate the safety and efficacy of bintrafusp alfa in Asian patients with pretreated, PD-L1-unselected esophageal SCC. PATIENTS AND METHODS In a phase 1 study, Asian patients with pretreated esophageal SCC received bintrafusp alfa 1200 mg every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was safety/tolerability with a goal of exploring clinical activity. RESULTS By the database cutoff of August 24, 2018, 30 patients (76.7% had two or more prior anticancer regimens) received bintrafusp alfa for a median of 6.1 weeks; two remained on treatment. Nineteen patients (63.3%) had treatment-related adverse events, seven (23.3%) with grade 3/4 events, and there were no treatment-related deaths. The confirmed objective response rate (ORR) per independent review was 10.0% (95% confidence interval [CI] 2.1-26.5); responses lasted 2.8-8.3 + months. All responses occurred in immune-excluded tumors. Investigator-assessed confirmed ORR was 20.0% (95% CI 7.7-38.6). Median overall survival was 11.9 months (95% CI 5.7-not reached). CONCLUSIONS Bintrafusp alfa demonstrated a manageable safety profile and efficacy in Asian patients with pretreated esophageal SCC. CLINICAL TRIALS REGISTRATION NCT02699515.
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Affiliation(s)
- Chia-Chi Lin
- National Taiwan University Hospital, Taipei, Taiwan
| | - Toshihiko Doi
- National Cancer Center Hospital East, Kashiwa, Japan
| | - Kei Muro
- Aichi Cancer Center Hospital, Nagoya, Japan
| | - Ming-Mo Hou
- Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Taito Esaki
- National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | | | - Hyun Cheol Chung
- Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | | | - Isabelle Dussault
- EMD Serono Research and Development Institute, Inc., Billerica, MA, USA
- An Affiliate of Merck KGaA, Darmstadt, Germany
| | - Motonobu Osada
- Merck Biopharma Co., Ltd., Tokyo, Japan
- An Affiliate of Merck KGaA, Darmstadt, Germany
| | - Shunsuke Kondo
- National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
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Inoue M, Shimizu Y, Ishikawa M, Abiko S, Shimoda Y, Tanaka I, Kinowaki S, Ono M, Yamamoto K, Ono S, Sakamoto N. Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism. World J Gastroenterol 2020; 26:6047-6056. [PMID: 33132654 PMCID: PMC7584065 DOI: 10.3748/wjg.v26.i39.6047] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/13/2020] [Accepted: 09/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) is an important risk factor for the development of esophageal squamous cell carcinoma (ESCC). It remains controversial whether human papillomavirus (HPV) infection contributes to the occurrence/development of ESCC. There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B (ADH1B) and ALDH2 genotypes was evaluated.
AIM To evaluate relationships between HPV infection and development of esophageal cancer, particularly early esophageal cancer, based on ADH1B/ALDH2 polymorphisms.
METHODS We conducted an exploratory retrospective study using new specimens, and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital. Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2. We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe.
RESULTS HPV was detected in 15 (10.3%) of the 145 patients with ESCC. HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1 + *2/*2 were 10.8% and 9.8%, respectively (P = 1.00). HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2 + *2/*2 were 12.0% and 10.0%, respectively (P = 0.72). HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1% and 8.7%, respectively (P = 0.68). HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8% and 8.3%, respectively (P = 0.59). The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPV-negative groups were 14.4% and 21.4% (P = 0.22), respectively.
CONCLUSION In the present situation, HPV status is considered to be less important than other risk factors, such as alcohol consumption, smoking habit, ADH1B/ALDH2 polymorphisms, and HPV status would therefore have no effect on ESCC risk management.
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Affiliation(s)
- Masaki Inoue
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Yuichi Shimizu
- Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Marin Ishikawa
- Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0808, Japan
- Department of Gastroenterology, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Satoshi Abiko
- Department of Gastroenterology and Hepatology, Hakodate Municipal Hospital, Hakodate, Hokkaido 041-8680, Japan
| | - Yoshihiko Shimoda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Ikko Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Sayoko Kinowaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Masayoshi Ono
- Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Keiko Yamamoto
- Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Shoko Ono
- Department of Gastroenterology, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
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Stelow EB, Dill EA, Davick JJ, McCabe MB, Shami VM. High-Grade Squamous Intraepithelial Lesion of the Gastroesophageal Junction Secondary to High-Risk Human Papillomavirus. Am J Clin Pathol 2019; 152:359-364. [PMID: 31216362 DOI: 10.1093/ajcp/aqz039] [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] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES Although the role of human papillomavirus (HPV) in the development of some carcinomas (eg, anogenital and oropharyngeal squamous cell carcinomas) is nondebatable, there is still significant controversy regarding the relationship of HPV and esophageal squamous cell carcinomas (SCCs). METHODS All cases were sampled at or near the gastroesophageal junctions in patients with reflux and/or known Barrett esophagus and appear to have been initially sampled "incidentally." Patients were all men, aged 56 to 80 years. None had a known history of other HPV-related disease. RESULTS We present four cases of high-grade squamous intraepithelial lesion of the gastroesophageal junction secondary to high-risk HPV that have identical histologic features to similar lesions of the anogenital tract. CONCLUSIONS Whether such lesions are at risk for developing into invasive SCC remains unclear.
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Affiliation(s)
- Edward B Stelow
- Department of Pathology, University of Virginia, Charlottesville
| | - Erik A Dill
- Department of Pathology, University of Virginia, Charlottesville
| | | | - Michael B McCabe
- Division of Gastroenterology, Department of Internal Medicine, University of Virginia, Charlottesville
| | - Vanessa M Shami
- Division of Gastroenterology, Department of Internal Medicine, University of Virginia, Charlottesville
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Araldi RP, Sant’Ana TA, Módolo DG, de Melo TC, Spadacci-Morena DD, de Cassia Stocco R, Cerutti JM, de Souza EB. The human papillomavirus (HPV)-related cancer biology: An overview. Biomed Pharmacother 2018; 106:1537-1556. [DOI: 10.1016/j.biopha.2018.06.149] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 06/24/2018] [Accepted: 06/27/2018] [Indexed: 02/07/2023] Open
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Water Carcinogenicity and Prevalence of HPV Infection in Esophageal Cancer Patients in Huaihe River Basin, China. Gastroenterol Res Pract 2018; 2018:2028986. [PMID: 29853858 PMCID: PMC5960546 DOI: 10.1155/2018/2028986] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 03/01/2018] [Accepted: 03/06/2018] [Indexed: 01/19/2023] Open
Abstract
Objective The incidence of the upper gastrointestinal tumor has increased rapidly during recent decades. The relationship between local water pollution and the tumor is still not much clear, so this study was conducted to further investigate the local water pollution and its influence on the malignant cell transformation. Prevalence of human papillomavirus (HPV) in local esophageal cancer (EC) patients was also analyzed in Shenqiu County for the first time. Methods Two-step cell transformation was used to study different sources of water in the malignant cell transformation, and the existence of 3-methylcholanthrene (3-MC) in water was analyzed from the river and shallow and deep wells. HPV DNA in tissue samples of EC patients was detected by polymerase chain reaction (PCR) and HPV diagnostic kit. Results The river water has higher cytotoxicity than the shallow well water and induced significant cell malignant transformation, while deep well water has not shown the malignant cell transformation. In Huaihe River water, the 3-MC concentration was found higher than shallow and deep wells. An HPV infection rate was found high in patients with esophageal cancer. Conclusion Long-term consumption of polluted water can induce malignant cell transformation, and the presence of HPV may be an important cause of cancer.
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MacIntyre CR, Shaw P, Mackie FE, Boros C, Marshall H, Barnes M, Seale H, Kennedy SE, Moa A, Hayen A, Chughtai AA, O'Loughlin EV, Stormon M. Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. Vaccine 2016; 34:4343-50. [PMID: 27406936 DOI: 10.1016/j.vaccine.2016.06.049] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 06/14/2016] [Accepted: 06/15/2016] [Indexed: 12/31/2022]
Abstract
AIM The aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. METHODS A multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5-18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti-HPV antibody levels were measured at baseline (before first dose), 7 and 24months after the first dose of vaccine. RESULTS Fifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV. CONCLUSION Immunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children. CLINICAL TRIAL REGISTRATION NCT02263703 (ClinicalTrials.gov).
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Affiliation(s)
- C Raina MacIntyre
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia; College of Public Service and Community Solutions, Arizona State University, USA.
| | - Peter Shaw
- Dept Gastroenterology Children's Hospital at Westmead, Hawkesbury Rd, Westmead NSW 2145, Australia
| | - Fiona E Mackie
- Nephrology, Sydney Children's Hospital, Randwick, High St, Randwick NSW 2031, Australia; School of Women's & Children's Health, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Christina Boros
- The Women's and Children's Hospital and Robinson Research Institute and School of Medicine, The University of Adelaide, 55 King William Road, North Adelaide 5006, Australia
| | - Helen Marshall
- The Women's and Children's Hospital and Robinson Research Institute and School of Medicine, The University of Adelaide, 55 King William Road, North Adelaide 5006, Australia
| | - Michelle Barnes
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Holly Seale
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Sean E Kennedy
- Nephrology, Sydney Children's Hospital, Randwick, High St, Randwick NSW 2031, Australia; School of Women's & Children's Health, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Aye Moa
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Andrew Hayen
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Abrar Ahmad Chughtai
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Edward V O'Loughlin
- Dept Gastroenterology Children's Hospital at Westmead, Hawkesbury Rd, Westmead NSW 2145, Australia
| | - Michael Stormon
- Dept Gastroenterology Children's Hospital at Westmead, Hawkesbury Rd, Westmead NSW 2145, Australia
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Türkay DÖ, Vural Ç, Sayan M, Gürbüz Y. Detection of human papillomavirus in esophageal and gastroesophageal junction tumors: A retrospective study by real-time polymerase chain reaction in an instutional experience from Turkey and review of literature. Pathol Res Pract 2015; 212:77-82. [PMID: 26608416 DOI: 10.1016/j.prp.2015.10.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 08/10/2015] [Accepted: 10/20/2015] [Indexed: 02/07/2023]
Abstract
Esophageal cancer is a poor-prognosis malignancy that ranks eighth among all cancer types, and its prevalence shows differences among geographical regions. Although the most important risk factors for esophageal carcinoma are alcohol and smoking, viral infections, particularly HPV infection, are also considered among etiological agents. Our study aims to detect the presence of HPV in esophageal cancers in our patient population and to investigate its correlation with clinico-pathological parameters. We investigated the presence of HPV-DNA by real-time polymerase chain reaction in a total of 52 patients with esophageal cancer. Subtype analysis was performed in positive cases and was correlated with selected clinico-pathological parameters. Five (9.6%) of 52 tumor samples, 3 squamous cell carcinomas (3/33 cases) and 2 adenocarcinomas (2/19 cases), were HPV-DNA-positive. Subtype analysis could be performed in four HPV-DNA-positive cases, of which three were HPV type-39 and 1 was type-16. The Marmara region, where the present study was carried out, is a region with low-moderate risk for esophageal cancer, and the prevalence of HPV-DNA in these tumors is similar to the prevalence of HPV-DNA reported in the literature for regions with similar risk. In conclusion, we detected HPV DNA in a subset of esophageal and gastroesophageal junction tumors. HPV infection may have a role in esophageal carcinogenesis and high-risk HPV subtypes can particularly be considered among risk factors since the prevalence of high risk HPV infection has also been found to be increased in regions with a high risk for esophageal cancer compared to low-moderate risk regions.
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Affiliation(s)
- Düriye Özer Türkay
- Department of Pathology, Ankara Numune Research and Education Hospital, Ankara, Turkey
| | - Çiğdem Vural
- Department of Pathology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
| | - Murat Sayan
- Kocaeli University Hospital, Clinical Laboratory, PCR Unit, Kocaeli, Turkey; Near East University, Research Center of Experimental Health Sciences, Nicasia, Northern Cyprus
| | - Yeşim Gürbüz
- Department of Pathology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
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Tang WR, Chen ZJ, Lin K, Su M, Au WW. Development of esophageal cancer in Chaoshan region, China: association with environmental, genetic and cultural factors. Int J Hyg Environ Health 2015; 218:12-8. [PMID: 25455641 DOI: 10.1016/j.ijheh.2014.10.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Revised: 10/16/2014] [Accepted: 10/16/2014] [Indexed: 02/05/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer by incidence worldwide. Although the cancer is located at a readily recognizable and accessible site in the body, it is the sixth most common cause of cancer death. The 1- and 5-year survival rates in China are 50% and 15%, respectively. Furthermore, the cancer has distinct geographic and etiological risk factors in different locations around the world. Since ESCC is highly prevalent in the Chaoshan (Southeastern) region of China, this report will focus on a review of risk factors for the cancer in this area. From the review, it is clear that some important and traditional factors are involved, e.g. environmental mutagens, genetic predisposition. However, unique factors, e.g. the drinking of very hot tea, may play an important role. This review highlights the role of complex risk factors (environmental, genetic and cultural) which contribute to the multistage development of cancer: localized injury, inflammation, mitogenesis, mutagenesis, carcinogenesis and eventually mortality. The latter is contributed by unnecessary delay in seeking medical care which may be culturally related. The review emphasizes the need to identify causal mechanisms for the complex carcinogenic process which can provide opportunity for prevention and treatment of this potentially curable cancer.
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Affiliation(s)
- W R Tang
- Department of Preventive Medicine, Shantou University Medical College, Shantou, China
| | - Z J Chen
- Department of Radiation Therapy, Cancer Hospital, Shantou University Medical College, Shantou, China
| | - Kun Lin
- Department of Preventive Medicine, Shantou University Medical College, Shantou, China
| | - Min Su
- Department of Pathology, Shantou University Medical College, Shantou, China..
| | - W W Au
- Department of Preventive Medicine, Shantou University Medical College, Shantou, China; MPH Education Center, Shantou University Medical College, Shantou, China.
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Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis. Epidemiol Infect 2014; 142:1119-37. [PMID: 24721187 DOI: 10.1017/s0950268814000016] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
SUMMARY The oncogenic potential of human papillomaviruses (HPV) is well known in the context of cervical carcinoma; however, their role in the development of oesophageal squamous cell carcinoma (OSCC) is less clear. We aimed to determine the extent of the association between HPV infection and OSCC. A comprehensive literature search found 132 studies addressing HPV and OSCC in human cases, and a meta-analysis was performed using a random-effects model. There was evidence of an increased risk of OSCC in patients with HPV infection [odds ratio (OR) 2·69, 95% confidence interval (CI) 2·05-3·54]. The prevalence of HPV in OSCC was found to be 24·8%. There was an increased risk associated with HPV-16 infection (OR 2·35, 95% CI 1·73-3·19). Subgroup analyses showed geographical variance, with Asia (OR 2·94, 95% CI 2·16-4·00), and particularly China (OR 2·85, 95% CI 2·05-3·96) being high-risk areas. Our results confirm an increase in HPV infection in OSCC cases.
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Li X, Gao C, Yang Y, Zhou F, Li M, Jin Q, Gao L. Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther 2014; 39:270-81. [PMID: 24308856 DOI: 10.1111/apt.12574] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Revised: 04/05/2013] [Accepted: 11/13/2013] [Indexed: 12/18/2022]
Abstract
BACKGROUND Human papillomavirus (HPV) infection might be one of the potential risk factors for oesophageal cancer. However, the previous epidemiological findings were heterogeneous. AIM To explore the association between HPV infection and oesophageal cancer risk by means of meta-analysis. METHODS Studies on HPV infection and oesophageal cancer were identified, the prevalence of HPV infection and its association with oesophageal cancer risk were quantitatively summarised by meta-analysis. RESULTS A total of 8990 oesophageal squamous cell carcinoma (SCC) patients and 174 oesophageal adenocarcinomas patients were evaluated from 76 included studies. Summarised HPV prevalence in oesophageal SCC was 22.2% [95% confidence interval (CI), 18.3-26.7%], HPV-16 was the most frequently observed subtype with a summarised prevalence of 11.4% (95% CI: 8.2-15.7%). With respect to oesophageal adenocarcinoma, HPV prevalence was 35.0% (95% CI, 13.2-65.7%) and HPV-16 prevalence was 11.4% (95% CI: 8.2-15.7%). Due to the limited number of included studies on oesophageal adenocarcinoma, association analyses were performed to oesophageal SCC only. Significant association was observed between HPV infection and oesophageal SCC with a summarised odds ratio of 3.32 (95% CI, 2.26-4.87). According to HPV-16, the strength of the association was found to be 3.52 (95% CI, 2.04-6.07). CONCLUSIONS Human papillomavirus infection was observed to be associated with an increased risk of oesophageal SCC in this meta-analysis. However, due to the evident heterogeneity observed between the included studies and the strength of the association not as strong as observed for cervical cancer and laryngeal cancer, further studies are needed to clarify the relation and its underlying mechanisms.
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Affiliation(s)
- X Li
- MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Affiliation(s)
- Xiaoqi Lin
- Department of Pathology, Northwestern University/Northwestern Memorial Hospital, 675 N St. Claire St, Galter Pavillion 7-132F, Chicago, IL, 60611, USA,
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Feng B, Awuti I, Deng Y, Li D, Niyazi M, Aniwar J, Sheyhidin I, Lu G, Li G, Zhang L. Human papillomavirus promotes esophageal squamous cell carcinoma by regulating DNA methylation and expression of HLA-DQB1. Asia Pac J Clin Oncol 2013; 10:66-74. [PMID: 24148080 DOI: 10.1111/ajco.12135] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2013] [Indexed: 12/15/2022]
Affiliation(s)
- Biao Feng
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Idiris Awuti
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Yanchao Deng
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Desheng Li
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Maidiniyeti Niyazi
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Julaiti Aniwar
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Ilyar Sheyhidin
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Guoqing Lu
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Gang Li
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
| | - Liwei Zhang
- Department of Thoracic Surgery; Xinjiang Medical University, First Affiliated Hospital; Urumqi China
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Abstract
Human papillomavirus (HPV) is strongly associated with squamous esophageal cancer. The potential role of HPV in Barrett's esophagus (BE) has been examined but remains unclear. The aim of the study was to determine the prevalence of HPV in esophageal and gastric tissues obtained from patients with and without BE. We designed a cross-sectional study was conducted with prospective enrollment of eligible patients scheduled for esophagogastroduodenoscopy (EGD). All participants had biopsies of endoscopic BE, squamous-lined esophagus, and stomach. Immunohistochemistry (IHC) on formalin-fixed and paraffin-embedded tissue was conducted using monoclonal antibodies. Polymerase chain reaction (PCR) for HPV was performed on DNA extracted from esophageal biopsies snapped frozen within 30 minutes after endoscopic capture. The Roche HPV Linear Array Assay with PGMY primers that has high sensitivity for detecting 37 types of HPV was used. A total of 127 subjects were included: 39 with definitive BE had IHC done on samples from non-dysplastic BE, squamous esophagus, gastric cardia, and gastric body; and 88 control patients without BE had IHC done on squamous esophageal samples, gastric cardia, and gastric body. HPV was not detected in any of the samples in either group. For confirmation, HPV DNA PCR was performed on randomly selected samples from 66 patients (both esophagus and BE from 13 patients with BE, and 53 esophagus from patients without BE); no sample had HPV DNA detected via PCR in the presence of adequate quality control. HPV infection does not play a role in the formation of non-dysplastic Barrett's esophagus in men in the United States.
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Affiliation(s)
- H. B. El-Serag
- Section of Gastroenterology and Hepatology at the Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - J. M. Hollier
- Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, Texas
| | - P. Gravitt
- Johns Hopkins School of Public Health, Baltimore, Maryland
| | - A. Alsarraj
- Section of Gastroenterology and Hepatology at the Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - M. Younes
- Department of Pathology, UT Medical School at Houston, Houston, Texas, USA
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Wang YF, Wang XS, Gao SG, Chen Q, Yang YT, Xiao ZY, Peng XQ, Hu XF, Wang QY, Feng XS. Clinical significance of combined detection of human papilloma virus infection and human telomerase RNA component gene amplification in patients with squamous cell carcinoma of the esophagus in northern China. Eur J Med Res 2013; 18:11. [PMID: 23634750 PMCID: PMC3644284 DOI: 10.1186/2047-783x-18-11] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2012] [Accepted: 04/03/2013] [Indexed: 11/29/2022] Open
Abstract
Background The aim of the study was to test for human papilloma virus (HPV) infection and human telomerase RNA component (hTERC) gene amplification in tissues derived from esophageal cancer, in esophagus displaying atypical hyperplasia and in normal tissue, and to analyze the relationship between them and discuss whether HPV infection and hTERC gene amplification play a role in the duration of survival of esophageal cancer patients. Methods To test for HPV infection, surface plasma resonance was used after extracting and subjecting the DNA to PCR amplification. Measurement of hTERC gene amplification was performed by the fluorescence in situ hybridization technique. Results The rates of HPV infection in the normal group, the atypical esophageal hyperplasia group and the cancer group were 0% (0/40), 10.00% (1/10) and 20.65% (19/92), respectively, with a statistically significant difference of P < 0.01. The hTERC gene amplification rate in normal tissue, grade I atypical hyperplastic tissue, grade II/III atypical hyperplastic tissue and esophageal cancer tissue were 0% (0/89), 15.38% (4/26), 47.06% (8/17) and 89.13% (82/92), respectively, with a statistically significant difference of P < 0.01. On follow-up of 92 patients, survival curves of the HPV-positive and HPV-negative groups were not significantly different (P > 0.05). Survival curves of the hTERC gene amplification-positive and hTERC gene amplification-negative groups were statistically significant (P < 0.05). A matching chi-square test showed that there was no correlation between HPV infection and hTERC gene amplification (P > 0.05). Conclusion HPV infection may be one of many factors contributing to the development of esophageal cancer, but it does not influence prognosis. Amplification of the hTERC gene appears to influence certain features associated with postoperative survival in esophageal carcinoma patients.
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Affiliation(s)
- Yu-Feng Wang
- Department of Oncology, First Affiliated Hospital, Cancer Institute, Henan University of Science and Technology, Luoyang, Henan Province, 471003, China
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17
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Effectiveness of unsedated transnasal endoscopy with white-light, flexible spectral imaging color enhancement, and lugol staining for esophageal cancer screening in high-risk patients. J Clin Gastroenterol 2013; 47:314-21. [PMID: 23059405 DOI: 10.1097/mcg.0b013e3182617fc1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Transnasal endoscopy (TNE) has been proposed to screen for esophageal squamous cell cancer (ESCC) in Asia. This study aimed to assess the feasibility and tolerance of Brazilian patients to undergo unsedated TNE for screening, the prevalence of ESCC in this population, and the effectiveness of white-light endoscopy (WLE) and digital chromoendoscopy [flexible spectral imaging color enhancement (FICE)] to diagnose esophageal neoplasia. PATIENTS AND METHODS This was a diagnostic test study that enrolled patients with head and neck squamous cell cancer (HNSCC) referred to ESCC screening. Patients' tolerance was rated by a numeric pain intensity scale. Interventions included unsedated TNE with WLE and FICE examination of the esophagus, in a tandem manner with blinded operators, followed by lugol chromoscopy. Performance of WLE and FICE for neoplasia detection was compared with the reference standard (lugol chromoscopy plus histology). RESULTS A total of 106 patients were recruited. TNE was feasible in 99.1%, and 92% of the patients rated the discomfort as absent or minimal. Thirteen ESCC were detected (12.3%), with 10 early cancers (77%). The tests showed an excellent performance and there was no difference between WLE (sensitivity 92.3%, specificity 98.9%, accuracy 98.1%, area under curve 0.995) and FICE (sensitivity 100%, specificity 98.9%, accuracy 99%, area under curve 0.956) for esophageal neoplasia detection. CONCLUSIONS Unsedated TNE is a feasible, well accepted, and efficient diagnostic tool for the screening of ESCC. The elevated rate of esophageal neoplasia strengthens the recommendations to screen patients with HNSCC. The yields of WLE and FICE were similar for ESCC detection.
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18
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Dąbrowski A, Kwaśniewski W, Skoczylas T, Bednarek W, Kuźma D, Goździcka-Józefiak A. Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region. World J Gastroenterol 2012; 18:5739-44. [PMID: 23155315 PMCID: PMC3484343 DOI: 10.3748/wjg.v18.i40.5739] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Revised: 07/30/2012] [Accepted: 08/03/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the prevalence of human papilloma virus (HPV) in esophageal squamous cell carcinoma (ESCC) in the south-eastern region of Poland.
METHODS: The study population consisted of 56 ESCC patients and 35 controls. The controls were patients referred to our department due to other non-esophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology. In the ESCC patients, samples were taken from normal mucosa (56 mucosa samples) and from the tumor (56 tumor samples). Tissue samples from the controls were taken from normal mucosa of the middle esophagus (35 control samples). Quantitative determination of DNA was carried out using a spectrophotometric method. Genomic DNA was isolated using the QIAamp DNA Midi Kit. HPV infection was identified following PCR amplification of the HPV gene sequence, using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV. The sequencing results were computationally analyzed using the basic local alignment search tool database.
RESULTS: In tumor samples, HPV DNA was identified in 28 of 56 patients (50%). High risk HPV phenotypes (16 or/and 18) were found in 5 of 56 patients (8.9%), low risk in 19 of 56 patients (33.9%) and other types of HPV (37, 81, 97, CP6108) in 4 of 56 patients (7.1%). In mucosa samples, HPV DNA was isolated in 21 of 56 patients (37.5%). High risk HPV DNA was confirmed in 3 of 56 patients (5.3%), low risk HPV DNA in 12 of 56 patients (21.4%), and other types of HPV in 6 of 56 patients (10.7%). In control samples, HPV DNA was identified in 4 of 35 patients (11.4%) with no high risk HPV. The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56 (50%) vs 4 of 35 (11.4%), P < 0.001]. In esophageal cancer patients, both in tumor and mucosa samples, the predominant HPV phenotypes were low risk HPV, isolated 4 times more frequently than high risk phenotypes [19 of 56 (33.9%) vs 5 of 56 (8.9%), P < 0.001]. A higher prevalence of HPV was identified in female patients (71.4% vs 46.9%). Accordingly, the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7 (42.9%) vs 2 of 49 (4.1%), P < 0.05]. Of the pathological characteristics, only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27 (74.1%) vs 8 of 29 (27.6%) for ulcerative or protruding macroscopic type, P < 0.05]. The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation, phases in depth of tumor infiltration, grades of nodal involvement and stages of tumor progression.
CONCLUSION: Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex, progressive, multifactorial and multistep esophageal carcinogenesis.
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19
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Interleukin 6 and C-reactive protein in esophageal cancer. Clin Chim Acta 2012; 413:1583-90. [PMID: 22609487 DOI: 10.1016/j.cca.2012.05.009] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Revised: 05/08/2012] [Accepted: 05/09/2012] [Indexed: 12/12/2022]
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20
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Zhuo W, Zhang L, Wang Y, Zhu B, Chen Z. Cyclin D1 G870A polymorphism is a risk factor for esophageal cancer among Asians. Cancer Invest 2012; 30:630-6. [PMID: 23020291 DOI: 10.3109/07357907.2012.726385] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Investigations concerning the association of Cyclin D1 (CCND1) G870A polymorphism with esophageal cancer risk have generated conflicting results. Thus, meta-analyses were conducted. The overall data suggest that CCND1 G870A variation might have an association with increased esophageal cancer susceptibility. In subgroup analyses on ethnicity, homozygous AA alleles might elevate esophageal cancer risk among Asians but not Caucasians. In subgroup analysis on histological types, no association was found in either the adenocarcinoma or the squamous cell carcinoma subgroup. Collectively, results suggest that CCND1 G870A polymorphism might be a low-penetrant risk factor for esophageal carcinoma, particularly among Asians.
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Affiliation(s)
- Wenlei Zhuo
- Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
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21
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Liyanage SS, Segelov E, Garland SM, Tabrizi SN, Seale H, Crowe PJ, Dwyer DE, Barbour A, Newall AT, Malik A, Macintyre CR. Role of human papillomaviruses in esophageal squamous cell carcinoma. Asia Pac J Clin Oncol 2012; 9:12-28. [PMID: 22897897 DOI: 10.1111/j.1743-7563.2012.01555.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2012] [Indexed: 12/14/2022]
Abstract
Esophageal cancer (EC) is responsible for almost half a million deaths worldwide annually and has a multifactorial etiology, which may account for its geographical variation in incidence. In the last 30 years the potential of human papillomaviruses (HPV) as oncogenes or co-factors in the tumorigenic process of esophageal squamous cell carcinoma (ESCC) has been widely studied. While the etiology of HPV in cervical and certain other anogenital and aerodigestive cancers has been established, results regarding its role in EC have been largely inconclusive. A causal association can be evaluated only with a case-control study, where normal controls are compared to ESCC cases for the presence of HPV. We reviewed all studies investigating ESCC tissue for HPV DNA and identified 139 that met our inclusion criteria, of which only 22 were case-control studies. Our results support previous findings of higher levels of HPV detection in high-risk ESCC regions than in areas of low risk. In addition, we confirm that the role of HPV in ESCC remains unclear, despite an accumulation of studies on the subject. The variations in investigative technique, study design and sample types tested may account for the lack of consistency in results. There is a need for a meta-analysis of all case-control studies to date, and for large, well-designed case-control studies with adequate power to investigate the association. The potential benefits of prophylactic HPV vaccines could be evaluated if HPV is identified as an etiological factor in EC, highlighting the need for further research in this area.
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Affiliation(s)
- Surabhi S Liyanage
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Randwick, Sydney, NSW 2052, Australia.
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22
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Syrjänen K. Geographic origin is a significant determinant of human papillomavirus prevalence in oesophageal squamous cell carcinoma: systematic review and meta-analysis. ACTA ACUST UNITED AC 2012; 45:1-18. [PMID: 22830571 DOI: 10.3109/00365548.2012.702281] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Since the first reports in 1982 suggesting an aetiological role for human papillomavirus (HPV) in a subset of oesophageal squamous cell carcinomas (ESCC), the literature reporting HPV detection in ESCC has expanded rapidly. However no formal meta-analysis of this literature has been published yet. The objective of this study was to perform a systematic review and formal meta-analysis of the literature reporting HPV detection in ESCC. METHODS MEDLINE and Current Contents were searched through March 2012. The effect size was calculated as event rates and their 95% confidence interval (95% CI), with homogeneity testing using Cochran's Q and I² statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin of study) on effect size, and potential publication bias was estimated using funnel plot symmetry (Begg and Mazumdar rank correlation, Egger's regression, and Duval and Tweedie's trim and fill method). RESULTS Of the 1177 abstracts found, 152 studies were determined to be eligible for this meta-analysis. These 152 studies covered a total of 10,234 ESCC cases, analysed by different HPV detection methods in different geographic regions. Of these 10,234 cases, 3135 (30.6%) tested HPV-positive, translating to an effect size of 0.372 (95% CI 0.360-0.384; fixed effects model) and 0.290 (95% CI 0.251-0.31; random effects model). When stratified by HPV detection technique, there was a significant heterogeneity between the studies, but importantly, the between-strata summary comparison was not significant (random effects model; p = 0.440). In contrast, there was significant heterogeneity between the studies from the different geographic regions. In the maximum likelihood meta-regression, HPV detection method was not a significant study-level covariate, in contrast to the geographic origin of the study, which had a significant impact (p = 0.00005) on the summary effect size estimates. No evidence for significant publication bias was found in funnel plot symmetry testing. In the sensitivity analysis, all meta-analytic results appeared robust to all (n = 151) one-by-one study removals. CONCLUSIONS These meta-analysis results indicate that the reported wide variability in HPV detection rates in ESCC is not due to the HPV detection techniques, but is explained by the geographic origin of the study. These data substantiate the recently elaborated concept that ESCC might have a different aetiology in low-incidence and high-incidence geographic regions, HPV playing an important role only in the latter.
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Affiliation(s)
- Kari Syrjänen
- Department of Oncology & Radiotherapy, Turku University Hospital, Turku, Finland.
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23
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Yahyapour Y, Shamsi-Shahrabadi M, Mahmoudi M, Siadati S, Shahryar SS, Shokri-Shirvani J, Mollaei H, Monavari SHR. Evaluation of Human Papilloma Virus Infection in Patients with Esophageal Squamous Cell Carcinoma from the Caspian Sea Area, North of Iran. Asian Pac J Cancer Prev 2012; 13:1261-6. [DOI: 10.7314/apjcp.2012.13.4.1261] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Abdirad A, Eram N, Behzadi AH, Koriyama C, Parvaneh N, Akiba S, Kato T, Kahn N, Ghofrani M, Sadigh N. Human papillomavirus detected in esophageal squamous cell carcinoma in Iran. Eur J Intern Med 2012; 23:e59-62. [PMID: 22284258 DOI: 10.1016/j.ejim.2011.06.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2011] [Revised: 06/16/2011] [Accepted: 06/17/2011] [Indexed: 01/17/2023]
Abstract
INTRODUCTION Considering the different results obtained regarding the association of HPV with the development of esophageal squamous cell carcinoma (ESCC) in different populations, we aimed to determine the frequency of HPV infection and its subtypes in ESCC in Iranian patients. METHOD A total of 100 paraffin-embedded tissue samples of ESCC diagnosed during 1991 and 2005 in the Institute of Cancer affiliated to Tehran University of Medical Sciences were selected. Seven out of 100 samples were excluded due to low quality of extracted DNA from paraffin-embedded specimens. Thus, 93 samples were included for HPV genotyping. RESULT All samples were examined using SPF10 primers for HPV detection. HPV DNA was positive in 8 out of 93 (8.6%) ESCC specimens. Using INNO-LiPA genotyping system we detected the genotypes of 5 out of 8 HPV-positive samples. Both HPV types 16 and 6 were detected in 3 specimens; one sample was positive for HPV type 18 and 2 samples were co-infected with two HPV types. There were no statistically significant differences between HPV-positive and HPV-negative cases with regard to clinical and pathologic findings. Three samples were positive for SPF10 indicating HPV infection; however, the exact HPV type could not be clarified using INNO-LiPA genotyping . CONCLUSION In conclusion, the present study showed that a small proportion of ESCC specimens from Iran harbor HPV16, 18 genome using a highly sensitive method. As different rates have been reported from Iran, a more widespread study with more precise definition of geographical differences could delineate the potential involvement of HPV in the development of ESCC in Iranian population.
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Affiliation(s)
- Afshin Abdirad
- Tehran University of Medical Sciences, The Cancer Research Center, Tehran, Iran.
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25
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Brown J, Bothma H, Veale R, Willem P. Genomic imbalances in esophageal carcinoma cell lines involve Wnt pathway genes. World J Gastroenterol 2011; 17:2909-23. [PMID: 21734802 PMCID: PMC3129505 DOI: 10.3748/wjg.v17.i24.2909] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Revised: 10/30/2010] [Accepted: 11/06/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify molecular markers shared across South African esophageal squamous cell carcinoma (ESCC) cell lines using cytogenetics, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) array copy number analysis.
METHODS: We used conventional cytogenetics, FISH, and multicolor FISH to characterize the chromosomal rearrangements of five ESCC cell lines established in South Africa. The whole genome copy number profile was established from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC software.
RESULTS: We detected common translocation breakpoints involving chromosomes 1p11-12 and 3p11.2, the latter correlated with the deletion, or interruption of the EPHA3 gene. The most significant amplifications involved the following chromosomal regions and genes: 11q13.3 (CCND1, FGF3, FGF4, FGF19, MYEOV), 8q24.21(C-MYC, FAM84B), 11q22.1-q22.3 (BIRC2, BIRC3), 5p15.2 (CTNND2), 3q11.2-q12.2 (MINA) and 18p11.32 (TYMS, YES1). The significant deletions included 1p31.2-p31.1 (CTH, GADD45α, DIRAS3), 2q22.1 (LRP1B), 3p12.1-p14.2 (FHIT), 4q22.1-q32.1 (CASP6, SMAD1), 8p23.2-q11.1 (BNIP3L) and 18q21.1-q21.2 (SMAD4, DCC). The 3p11.2 translocation breakpoint was shared across four cell lines, supporting a role for genes involved at this site, in particular, the EPHA3 gene which has previously been reported to be deleted in ESCC.
CONCLUSION: The finding that a significant number of genes that were amplified (FGF3, FGF4, FGF19, CCND1 and C-MYC) or deleted (SFRP2 gene) are involved in the Wnt and fibroblast growth factor signaling pathways, suggests that these pathways may be activated in these cell lines.
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26
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Zhang QY, Zhang DH, Shen ZY, Xu LY, Li EM, Au WW. Infection and integration of human papillomavirus in esophageal carcinoma. Int J Hyg Environ Health 2011; 214:156-61. [PMID: 21130683 DOI: 10.1016/j.ijheh.2010.11.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2010] [Revised: 10/02/2010] [Accepted: 11/02/2010] [Indexed: 02/05/2023]
Abstract
Infection with human papillomavirus (HPV) could be a suspected or potential modifiable risk factor in esophageal carcinoma (EC) but findings have not been consistent. We therefore investigated the epidemiology of HPV infection and integration in the pathogenesis of esophageal carcinoma (EC) in the Shantou region, China. This was a retrospective study involving nested PCR to evaluate HPV presence, HPV genotyping, and analyzing HPV-16 integration status in esophageal tumor tissues (n=106) and paired tumor-adjacent normal tissues, as well as normal esophagus tissue from control subjects (n=100). The detection rates of HPV DNA in EC and tumor-adjacent tissue were significantly higher than that in normal controls (77.4% and 80.2% vs. 33.0%). HPV infection was mainly found in adults, ages 35-47 years old, and the infection rate was negatively associated with the age of EC patients (P-trend<0.05). In addition, the HPV infection rates in patients who smoked was 3.27 times higher than in non-smoking patients (84.9% vs. 67.4%, P<0.05) but was not associated with gender, alcohol consumption, tumor grade or lymph-node metastasis of EC patients. The distribution of HPV genotypes in patients from high to low proportion was HPV-16, -58, -18, -33, -31 and -11. Infection with multiple HPV genotypes mainly included HPV-16/-18 and HPV-16/-33. The integration rate of HPV-16 in EC tissue was higher than that in tumor-adjacent and control tissues (93.4% vs. 50.9% and 45.5%). Our findings indicate that infection with HPV, especially the high-risk HPV, and their integration suggest an association in malignant transformation of EC in the high-incidence EC region in Shantou, China.
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Affiliation(s)
- Qing-Ying Zhang
- Department of Preventive Medicine, Shantou University Medical College, Shantou, China.
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Malik SM, Nevin DT, Cohen S, Hunt JL, Palazzo JP. Assessment of immunohistochemistry for p16INK4 and high-risk HPV DNA by in situ hybridization in esophageal squamous cell carcinoma. Int J Surg Pathol 2010; 19:31-4. [PMID: 21087981 DOI: 10.1177/1066896910382005] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The role of high-risk human papillomavirus (HPV) in the pathogenesis of esophageal squamous cell carcinoma (ESCC) remains unclear. p16(INK4) is used as a surrogate marker to detect HPV-related tumors but has had discrepant results in ESCC. In this study, 32 cases of ESCC were examined to determine the relationship between p16(INK4) expression and high-risk HPV. All the tumors were stained by immunohistochemistry for p16(INK4). Tumors having p16(INK4) nuclear and/or nuclear and cytoplasmic expression were considered positive. Tumors positive for p16(INK4) expression were tested for high-risk HPV by in situ hybridization (ISH). In all, 20 cases of ESCC (63%) showed only cytoplasmic staining for p16(INK4), and 11 cases (34%) showed both cytoplasmic and nuclear staining for p16(INK4); 4 cases (13%) showed no staining for p16(INK4). None of the p16(INK4) -positive cases were positive for high-risk HPV by ISH. These results indicate that p16(INK4) expression in ESCC does not correlate with the presence of high-risk HPV DNA by ISH. High-risk HPV does not seem to play a major role in the carcinogenesis of ESCC in low-risk areas.
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Affiliation(s)
- Sajjad M Malik
- Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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Vaccination against human papilloma virus (HPV): epidemiological evidence of HPV in non-genital cancers. Pathol Oncol Res 2010; 17:103-19. [PMID: 20640607 DOI: 10.1007/s12253-010-9288-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2010] [Accepted: 06/23/2010] [Indexed: 10/19/2022]
Abstract
Recently, the vaccine against human papillomavirus (HPV) was introduced in the national vaccination programmes of several countries worldwide. The established association between HPV and the progression of cervical neoplasia provides evidence of the expected protection of the vaccine against cervical cancer. During the last two decades several studies have also examined the possible involvement of HPV in non-genital cancers and have proposed the presence of HPV in oesophageal, laryngeal, oropharyngeal, lung, urothelial, breast and colon cancers. The possible involvement of HPV in these types of cancer would necessitate the introduction of the vaccine in both boys and girls. However, the role of HPV in the pathogenesis of these types of cancer has yet to be proven. Moreover, the controversial evidence of the possible impact of the vaccination against HPV in the prevention of non-genital cancers needs to be further evaluated. In this review, we present an overview of the existing epidemiological evidence regarding the detection of HPV in non-genital cancers.
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Tonna J, Palefsky JM, Rabban J, Campos GM, Theodore P, Ladabaum U. Esophageal verrucous carcinoma arising from hyperkeratotic plaques associated with human papilloma virus type 51. Dis Esophagus 2010; 23:E17-20. [PMID: 20626449 DOI: 10.1111/j.1442-2050.2010.01087.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal verrucous carcinoma is a rare variant of esophageal squamous cell carcinoma. We report a case of esophageal verrucous carcinoma associated with human papilloma virus (HPV) type 51. The patient had long-standing dysphagia and odynophagia, and white esophageal plaques showing hyperkeratosis on biopsy. At repeat endoscopy, the esophagus was covered with verrucous white plaques and areas of nodular mucosa with white fronds, with a distal 10-cm smooth mass protruding into the lumen. Biopsies demonstrated an atypical squamoproliferative lesion but no frank malignancy. HPV type 51 DNA was detected in endoscopic biopsy specimens by polymerase chain reaction. Because the size of the lesion favored an underlying verrucous carcinoma, our patient underwent minimally invasive esophagectomy with gastric pull-up and cervical anastomosis. The pathologic diagnosis was a well-differentiated esophageal verrucous carcinoma. One year after esophagectomy, the patient feels well and is free of disease. Although HPV DNA was not detected in the cancer tissue obtained at surgery, our case suggests an association between HPV type 51 and esophageal verrucous carcinoma. The clinical evolution in this case highlights the importance of endoscopic surveillance in patients with exuberant esophageal hyperkeratosis, and of definitive surgical resection when malignancy is suspected even if frank malignancy is not demonstrated on superficial biopsies.
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Affiliation(s)
- J Tonna
- School of Medicine, University of California, San Francisco, California, USA
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Basaloid squamous cell carcinoma of the esophagus: assessment for high-risk human papillomavirus and related molecular markers. Am J Surg Pathol 2009; 33:1608-14. [PMID: 19738459 DOI: 10.1097/pas.0b013e3181b46fd4] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Basaloid squamous cell carcinoma (BSCC) of the esophagus is rare, historically confused for adenoid cystic carcinoma, and recently shown to behave similar to conventional, keratinizing esophageal squamous cell carcinoma. At other sites (eg, oropharynx, anogenital tract) the basaloid phenotype is frequently associated with the presence of high-risk human papillomavirus (HPV). HPVs role in esophageal squamous cell carcinomas is less certain, and to our knowledge, a direct examination of esophageal BSCC for high-risk HPV has not been performed earlier. Nine cases of esophageal BSCC were retrieved from our surgical pathology files. Twenty-two cases of keratinizing esophageal squamous cell carcinoma served as controls. In situ hybridization (ISH) for high-risk HPV and immunohistochemistry for related molecular markers including p53, cyclin D1, and p16 (scored 0 to 4+ based on percentage of cells staining; p53 additionally scored for intensity) were performed. HPV ISH was nonreactive in all tested cases. Compared with controls, BSCC showed less immunoreactivity for p16 and p53 (P=0.003, 0.009). Esophageal BSCC is negative for high-risk HPV by ISH, distinguishing these lesions from other BSCCs. Differential p16 and p53 expression in BSCC suggests that these tumors are molecularly distinct from conventional esophageal squamous cell carcinomas.
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A non-synonymous coding SNP Lys45Glu of mmp3 associated with ESCC genetic susceptibility in population of Henan, China. ACTA ACUST UNITED AC 2009. [DOI: 10.1007/s10330-009-0131-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Herrera-Goepfert R, Lizano M, Akiba S, Carrillo-García A, Becker-D’Acosta M. Human papilloma virus and esophageal carcinoma in a Latin-American region. World J Gastroenterol 2009; 15:3142-7. [PMID: 19575494 PMCID: PMC2705737 DOI: 10.3748/wjg.15.3142] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the presence of high-risk human papilloma virus (HPV) in esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican population.
METHODS: Cases with a pathological diagnosis of squamous cell carcinoma of the esophagus were obtained from Department of Pathology files, at the National Cancer Institute in Mexico City during the period between 2000 and 2008. Slides from each case were reviewed and cases with sufficient neoplastic tissue were selected for molecular analysis. DNA was extracted from paraffin-embedded tissue samples for polymerase chain reaction analysis to detect HPV DNA sequences. Demographic and clinical data of each patient were retrieved from corresponding clinical records.
RESULTS: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected in one case. Unfortunately, HPV genotype could not be established in three cases due to lack of material for direct sequencing, although universal primers detected the presence of HPV generic sequences. No low-risk HPV genotypes were found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage. Male patients were most commonly affected and the male:female ratio in HPV-positive ESCC increased two-fold in comparison with HPV-negative cases (6.5:1 vs 3.1:1).
CONCLUSION: High prevalence of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV-associated ESCC is more common in areas with higher ESCC incidence rates.
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Abstract
This article reviews the environmental risk factors and predisposing conditions for the two main histologic types of esophageal cancer. Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of esophageal squamous cell carcinoma. Results of investigations on other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and, probably, absence of H pylori in the stomach increase the risk of esophageal adenocarcinoma. Results of studies investigating other factors are also discussed.
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Affiliation(s)
- Farin Kamangar
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 3034, Bethesda, MD 20892-7232, Phone: (301) 594-2936,
| | - Wong-Ho Chow
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 8100, Bethesda, MD 20892-7240, Phone: (301) 435-4708,
| | - Christian Abnet
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 3042, Bethesda, MD 20892-7232, Phone: (301) 594-1511,
| | - Sanford Dawsey
- Division of Cancer Epidemiology and Genetics, NCI, 6120 Executive Blvd., Room 3024, Bethesda, MD 20892-7232, Phone: (301) 594-2930,
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Mulvany NJ, Allen DG, Wilson SM. Diagnostic utility of p16INK4a: a reappraisal of its use in cervical biopsies. Pathology 2008; 40:335-44. [PMID: 18446622 DOI: 10.1080/00313020802035907] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
p16(INK4a), an indirect marker of cell cycle dysregulation, is commonly expressed in cervical dysplasias and carcinomas associated with high risk human papillomavirus (HR-HPV) infections. Although p16(INK4a) immunohistology is routinely used as a cost effective surrogate marker, many of the published articles are confusing and contradictory. The discrepancies can be ascribed to a multitude of factors operating at the molecular, technical and interpretative levels. In the first place, our simplistic model of viral mediated oncogenesis is speculative and fails to account for all the known biomolecular changes. Unresolved technical issues include the variables of tissue fixation, antibody dilution, antibody isotype and clone, and the sensitivity of the particular detection method. Within any controlled staining method, strong diffuse or 'block' immunoreactivity in squamous cells may be found in moderate/severe dysplasia (CIN 2/3) and invasive squamous carcinoma. In contrast, focal or multifocal reactivity in squamous cells may be artefactual, related to low risk or HR-HPV. p16(INK4a) is less reliable when dealing with glandular lesions since considerable overlap exists between reactive and dysplastic lesions. In addition not all glandular dysplasias/carcinomas are HR-HPV related, nor are all p16(INK4a) immunoreactive lesions associated with HR-HPV. We conclude that p16(INK4a) immunoperoxidase shows greater specificity than sensitivity for squamous lesions; in comparison, glandular dysplasias/carcinomas show reduced specificity and sensitivity. Like all cell cycle regulatory proteins, the future diagnostic role of p16(INK4a) is limited. The ideal diagnostic molecular test for cervical dysplasias will detect a HR-HPV related product after, but not before, cell transformation and will reliably predict those cases yet to experience disease progression.
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Affiliation(s)
- Nicholas J Mulvany
- Department of Anatomical Pathology, Austin Hospital, Heidelberg, Vic 3084, Australia.
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Human papillomavirus in esophageal squamous cell carcinoma of the high-risk Kazakh ethnic group in Xinjiang, China. Eur J Surg Oncol 2008; 34:765-70. [DOI: 10.1016/j.ejso.2007.11.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2007] [Accepted: 11/14/2007] [Indexed: 01/26/2023] Open
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Kollarova H, Machova L, Horakova D, Janoutova G, Janout V. Epidemiology of esophageal cancer--an overview article. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2008; 151:17-20. [PMID: 17690734 DOI: 10.5507/bp.2007.003] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Esophageal cancer is one of the most serious tumor diseases worldwide, owing to its rapid development and fatal prognosis in most cases. To compare epidemiologic characteristics, data published by the International Agency for Research on Cancer, Lyon, France and data from Masaryk Memorial Cancer Institute, Brno, Czech Republic were used. METHODS We conducted a search of selected Czech and foreign literature focused on the epidemiology of esophageal cancer and its main risk factors. RESULTS AND CONCLUSION An overview of esophageal cancer epidemiology is presented. Prevention of esophageal cancer should be based on early detection and surveillance of precancerous lesions, especially of Barrett's esophagus, and attention should also focus on modification of changeable risk factors, including tobacco smoking, alcohol abuse, and ingestion of hot and spicy food. Carefully designed epidemiologic studies, both descriptive and analytical, are required to increase understanding of the complexity of esophageal cancer etiology.
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Affiliation(s)
- Helena Kollarova
- Department of Preventive Medicine, Faculty of Medicine, Palacky University Olomouc, Hnevotinska 3, Olomouc 775 15, Czech Republic.
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Strati K, Lambert PF. HUMAN PAPILLOMAVIRUS ASSOCIATION WITH HEAD AND NECK CANCERS: UNDERSTANDING VIRUS BIOLOGY AND USING IT IN THE DEVELOPMENT OF CANCER DIAGNOSTICS. ACTA ACUST UNITED AC 2008; 2:11-20. [PMID: 20419065 DOI: 10.1517/17530059.2.1.11] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The link between human papillomaviruses and human cervical cancers has long been established. However, human papillomaviruses (HPVs) are now being detected in another type of cancer, not previously associated with this virus, head and neck squamous cell carcinoma (HNSCC). This review will focus on experimental data supporting the view that HPVs contribute to the etiology of a subset of HNSCC. We further put forth the argument that HPV-associated HNSCC deserves to be recognized as a distinct disease in the clinic and as such needs to be appropriately diagnosed. We offer an overview of studies that have helped dissect the role of HPVs in HNSCC and that may be helpful in the development of new diagnostic tools for discriminating this type of HNSCC.
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Affiliation(s)
- Katerina Strati
- McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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Shuyama K, Castillo A, Aguayo F, Sun Q, Khan N, Koriyama C, Akiba S. Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China. Br J Cancer 2007; 96:1554-9. [PMID: 17453003 PMCID: PMC2359949 DOI: 10.1038/sj.bjc.6603765] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
To examine the potential roles of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (ESCC) development, we examined the presence of HPV DNA in paraffin-embedded ESCC tissues collected from two areas with different ESCC incidence rates in China, that is, Gansu (n=26) and Shandong (n=33), using PCR with SPF10 primers, or PCR with GP5+/GP6+ primers combined with Southern blot hybridisation. HPV genotype was determined by the INNO-LiPA HPV genotyping kit. HPV DNA was detected in 17 cases (65%) in Gansu, where ESCC incidence is much higher than in Shandong, where HPV was positive in two samples (6%). HPV genotypes 16 and 18 were detected in 79 and 16% of HPV-positive samples, respectively. Real-time PCR analysis suggested the presence of integrated form of HPV DNA in all the HPV-16-positive samples, but its viral load was estimated to be only <1–2 copies cell−1. We could not detect HPV 16/18 E6 protein expression by immunostaining in any of the HPV-16-positive samples. Neither p16INK4a nor p53 expression was related to HPV presence in ESCCs. Further studies seem warranted to examine the possible aetiological roles of HPV in ESCC.
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Affiliation(s)
- K Shuyama
- Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
| | - A Castillo
- Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
| | - F Aguayo
- Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
| | - Q Sun
- Division of Radiation Epidemiology, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Deshengmenwai, Xicheng District, Beijing 100088, China
| | - N Khan
- Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
| | - C Koriyama
- Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
| | - S Akiba
- Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
- E-mail:
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