Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran
- 220 Downloads
- 3 Citations
Abstract
Human papillomavirus (HPV) infection is one of the hypothesized causes of esophageal squamous cell carcinoma (ESCC), but the etiological association remains uncertain. It was postulated that other infectious agents together with HPV may increase the risk of ESCC. The current investigation aimed to explore the presence of a new human tumor virus, Merkel cell polyomavirus (MCPyV), together with HPV in ESCC tumors and non-cancerous esophageal samples in northern Iran. In total, 96 esophageal samples (51 with ESCC, and 45 without esophageal malignancy) were examined. HPV DNA was detected in esophageal specimens of 16 out of the 51 ESCC cases (31.4 %) and 20 out of the 45 non-cancerous samples (44.4 %). Untypable HPV genotypes were recognized in high rates in cancerous (75.0 %) and non-cancerous (55.0 %) esophageal specimens. MCPyV DNA was detected in esophageal specimens of 23 out of the 51 ESCC cases (45.1 %) and 16 out of the 45 non-cancerous samples (35.6 %). The mean MCPyV DNA copy number was 1.0 × 10−5 ± 2.4 × 10−5 and 6.0 × 10−6 ± 1.3 × 10−5 per cell in ESCC cases and non-cancerous samples, respectively. There was no statistically significant difference between cancerous and non-cancerous samples regarding mean MCPyV DNA load (P = 0.353). A bayesian logistic regression model adjusted to the location of esophageal specimen and MCPyV infection, revealed a significant association between HPV and odds of ESCC (OR, 2.45; 95 % CI: 1.01–6.16). This study provides the evidence of the detection of the MCPyV DNA at a low viral copy number in cancerous and non- cancerous esophageal samples.
Keywords
Esophageal squamous cell carcinoma Merkel cell polyomavirus Human papillomavirus Oncogenic virusesNotes
Acknowledgments
We would like to express our appreciation to the directors and staff of Pathology Department of Shahid Beheshti Hospital, and Amol Central Pathobiology Laboratory for their collaboration in sample collection. This study was financially supported by a grant from Babol University of Medical Sciences (Project code: 9339317).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
References
- 1.Lambert R, Hainaut P (2007) Esophageal cancer: cases and causes (part I). Endoscopy 39(6):550–555CrossRefPubMedGoogle Scholar
- 2.Holmes RS, Vaughan TL (2007) Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol 17(1):2–9CrossRefPubMedGoogle Scholar
- 3.Wei WQ et al. (2004) Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Am J Clin Nutr 79(1):80–85PubMedGoogle Scholar
- 4.Al-Haddad S et al. (2014) Infection and esophageal cancer. Ann N Y Acad Sci 1325:187–196CrossRefPubMedGoogle Scholar
- 5.Guo F et al. (2012) Human papillomavirus infection and esophageal squamous cell carcinoma: a case-control study. Cancer Epidemiol Biomarkers Prev 21(5):780–785CrossRefPubMedGoogle Scholar
- 6.Yahyapour Y et al. (2013) High-risk and low-risk human papillomavirus in esophageal squamous cell carcinoma at Mazandaran, Northern Iran. Pathol Oncol Res 19(3):385–391CrossRefPubMedGoogle Scholar
- 7.Cao B et al. (2005) LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China. Carcinogenesis 26(7):1280–1284CrossRefPubMedGoogle Scholar
- 8.Moens U, Van Ghelue M, Ehlers B (2014) Are human polyomaviruses co-factors for cancers induced by other oncoviruses? Rev Med Virol 24(5):343–360CrossRefPubMedGoogle Scholar
- 9.Salehi-Vaziri M et al. (2015) Merkel cell polyomavirus and human papillomavirus infections in cervical disease in Iranian women. Arch Virol 160(5):1181–1187CrossRefPubMedGoogle Scholar
- 10.Feng H et al. (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319(5866):1096–1100CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Tachibana T (1995) The Merkel cell: recent findings and unresolved problems. Arch Histol Cytol 58(4):379–396CrossRefPubMedGoogle Scholar
- 12.Harmse JL et al. (1999) Merkel cells in the human oesophagus. J Pathol 189(2):176–179CrossRefPubMedGoogle Scholar
- 13.Wieland U et al. (2009) Merkel cell polyomavirus DNA in persons without merkel cell carcinoma. Emerg Infect Dis 15(9):1496–1498CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Loyo M et al. (2010) Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission. Int J Cancer 126(12):2991–2996PubMedPubMedCentralGoogle Scholar
- 15.Iaconelli M et al. (2015) First detection of human papillomaviruses and human polyomaviruses in river waters in Italy. Food Environ Virol 7(4):309–315Google Scholar
- 16.Yahyapour Y et al. (2012) 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 13(4):1261–1266CrossRefPubMedGoogle Scholar
- 17.Sadeghi F et al. (2015) Detection of Merkel cell polyomavirus large T-antigen sequences in human central nervous system tumors. J Med Virol 87(7):1241–1247Google Scholar
- 18.Sadeghi F. et al. Prevalence of JC polyomavirus large T antigen sequences among Iranian patients with central nervous system tumors. Arch Virol; 160(1): 61–68Google Scholar
- 19.Becker JC et al. (2009) MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol 129(1):248–250CrossRefPubMedGoogle Scholar
- 20.Imajoh M et al. (2012) Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients. Virol J 9:154CrossRefPubMedPubMedCentralGoogle Scholar
- 21.R Development Core Team (2005) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org
- 22.Parkin DM et al. (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108CrossRefPubMedGoogle Scholar
- 23.Blot WJ, McLaughlin JK (1999) The changing epidemiology of esophageal cancer. Semin Oncol 26(5 Suppl 15):2–8PubMedGoogle Scholar
- 24.Matsha T et al. (2007) Expression of p53 and its homolog, p73, in HPV DNA positive oesophageal squamous cell carcinomas. Virology 369(1):182–190CrossRefPubMedGoogle Scholar
- 25.Li X et al. (2014) Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther 39(3):270–281CrossRefPubMedGoogle Scholar
- 26.Zhang SK et al. (2015) The association between human papillomavirus 16 and esophageal cancer in Chinese population: a meta-analysis. BMC Cancer 15:1096PubMedGoogle Scholar
- 27.Sichero L et al. (2013) Broad HPV distribution in the genital region of men from the HPV infection in men (HIM) study. Virology 443(2):214–217CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Spinillo A et al. (2014) Untypable human papillomavirus infection and risk of cervical intraepithelial neoplasia among women with abnormal cervical cytology. J Med Virol 86(7):1145–1152CrossRefPubMedGoogle Scholar
- 29.McNees AL et al. (2005) Specific and quantitative detection of human polyomaviruses BKV, JCV, and SV40 by real time PCR. J Clin Virol 34(1):52–62CrossRefPubMedGoogle Scholar
- 30.Moore PS, Chang Y (2010) Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer 10(12):878–889CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Shuda M et al. (2008) T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci U S A 105(42):16272–16277CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Houben R et al. (2010) Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens. J Virol 84(14):7064–7072CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Sihto H et al. (2011) Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma. Clin Cancer Res 17(14):4806–4813CrossRefPubMedGoogle Scholar
- 34.Goh S et al. (2009) Merkel cell polyomavirus in respiratory tract secretions. Emerg Infect Dis 15(3):489–491CrossRefPubMedPubMedCentralGoogle Scholar