Skip to main content
Top
Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

Detection and genotype analysis of human papillomavirus in non-small cell lung cancer patients

Authors: Emmanouela Sarchianaki, Stavros P. Derdas, Markos Ntaoukakis, Elena Vakonaki, Eleni D. Lagoudaki, Ismini Lasithiotaki, Anna Sarchianaki, Anastasios Koutsopoulos, Emmanouil K. Symvoulakis, Demetrios A. Spandidos, Katerina M. Antoniou, George Sourvinos

Published in: Tumor Biology | Issue 4/2014

Login to get access

Abstract

Although the role of human papillomavirus (HPV) in the development of uterine cervical cancer is well established, the role of HPV in lung carcinogenesis remains controversial. The detection rates of HPV DNA are subject to a wide variation from 0 to 100 %. This is partly influenced by the detection techniques employed. To elucidate the impact of HPV infection on lung parenchyma, we analyzed 100 non-small cell lung cancer (NSCLC) specimens (39 squamous cell carcinomas, 50 adenocarcinomas, 5 samples with characteristics of both squamous cell and adenocarcinoma, 5 undifferentiated and 1 large cell carcinoma) from the region of Crete, Greece. Sixteen non-cancerous samples served as the negative controls. DNA was extracted from 100 paraffin-embedded tissue sections obtained from NSCLC patients. The specimens were examined for the detection of HPV DNA by Real-Time PCR using GP5+/GP6+ primers. Furthermore, the HPV-positive samples were subjected to genotyping. In contrast to the absence of viral genomes in the control samples, HPV DNA was detected in 19 NSCLC specimens (19 %). In particular, 4 squamous cell carcinomas, 12 adenocarcinomas, 1 sample with characteristics of both squamous cell and adenocarcinoma, and 2 undifferentiated samples were HPV-positive. The distribution of HPV genotypes was as follows: HPV 16: eight cases (42.1 %); HPV 11: three cases (15.8 %); HPV 6: one case (5.2 %); HPV 59: one case (5.2 %); HPV 33: two cases (10.5 %); HPV 31: two cases (10.5 %) and HPV 18: two cases (10.5 %). The presence of HPV in the tumor samples provides evidence of the potential role of HPV in NSCLC and strongly argues for additional research on this issue.
Literature
1.
go back to reference Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol. 2012;13:790–801.PubMedCrossRef Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol. 2012;13:790–801.PubMedCrossRef
2.
go back to reference Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet. 1997;349:1498–504.PubMedCrossRef Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet. 1997;349:1498–504.PubMedCrossRef
3.
go back to reference de Villiers E-M, Fauquet C, Broker TR, Bernard H-U, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324:17–27.PubMedCrossRef de Villiers E-M, Fauquet C, Broker TR, Bernard H-U, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324:17–27.PubMedCrossRef
4.
go back to reference Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology. 2010;401:70–9.PubMedCentralPubMedCrossRef Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology. 2010;401:70–9.PubMedCentralPubMedCrossRef
5.
go back to reference Muñoz N, Bosch FX, Castellsagué X, Díaz M, de Sanjose S, Hammouda D, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer. 2004;111:278–85.PubMedCrossRef Muñoz N, Bosch FX, Castellsagué X, Díaz M, de Sanjose S, Hammouda D, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer. 2004;111:278–85.PubMedCrossRef
6.
go back to reference Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine. 2006;24:11–25.CrossRef Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine. 2006;24:11–25.CrossRef
7.
go back to reference Bosch FX, Lorincz A, Muñoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55:244–65.PubMedCentralPubMedCrossRef Bosch FX, Lorincz A, Muñoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55:244–65.PubMedCentralPubMedCrossRef
8.
go back to reference Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci. 2006;110:525–41.PubMedCrossRef Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci. 2006;110:525–41.PubMedCrossRef
9.
go back to reference Brink AA, Snijders PJ, Meijer CJ, Berkhof J, Verheijen RH. HPV testing in cervical screening. Best Pract Res Clin Obstet Gynaecol. 2006;20:253–66.PubMedCrossRef Brink AA, Snijders PJ, Meijer CJ, Berkhof J, Verheijen RH. HPV testing in cervical screening. Best Pract Res Clin Obstet Gynaecol. 2006;20:253–66.PubMedCrossRef
10.
go back to reference zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst. 2000;92:690–8.PubMedCrossRef zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst. 2000;92:690–8.PubMedCrossRef
11.
go back to reference Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004;78:11451–60.PubMedCentralPubMedCrossRef Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004;78:11451–60.PubMedCentralPubMedCrossRef
12.
go back to reference Garner-Hamrick PA, Fostel JM, Chien WM, Banerjee NS, Chow LT, Tr B, et al. Global effects of human papillomavirus type 18 E6/E7 in an organotypic keratinocyte culture system. J Virol. 2004;78:9041–50.PubMedCentralPubMedCrossRef Garner-Hamrick PA, Fostel JM, Chien WM, Banerjee NS, Chow LT, Tr B, et al. Global effects of human papillomavirus type 18 E6/E7 in an organotypic keratinocyte culture system. J Virol. 2004;78:9041–50.PubMedCentralPubMedCrossRef
14.
go back to reference Mammas IN, Sourvinos G, Zaravinos A, Spandidos DA. Vaccination against human papilloma virus (HPV): epidemiological evidence of HPV in non-genital cancers. Pathol Oncol Res. 2011;17:103–19.PubMedCrossRef Mammas IN, Sourvinos G, Zaravinos A, Spandidos DA. Vaccination against human papilloma virus (HPV): epidemiological evidence of HPV in non-genital cancers. Pathol Oncol Res. 2011;17:103–19.PubMedCrossRef
15.
go back to reference Klein F, Amin Kotb WF, Petersen I. Incidence of human papilloma virus in lung cancer. Lung Cancer. 2009;65:13–8.PubMedCrossRef Klein F, Amin Kotb WF, Petersen I. Incidence of human papilloma virus in lung cancer. Lung Cancer. 2009;65:13–8.PubMedCrossRef
16.
go back to reference Sourvinos G, Mammas IN, Derdas S, Spandidos DA. Human papillomaviruses (HPVs) in lung cancer: a causative trigger or just a co-incidence? Lung Cancer. 2013;79:95–6.PubMedCrossRef Sourvinos G, Mammas IN, Derdas S, Spandidos DA. Human papillomaviruses (HPVs) in lung cancer: a causative trigger or just a co-incidence? Lung Cancer. 2013;79:95–6.PubMedCrossRef
17.
go back to reference Syrjänen K. Detection of human papillomavirus in lung cancer: systematic review and meta-analysis. Anticancer Res. 2012;32:3235–50.PubMed Syrjänen K. Detection of human papillomavirus in lung cancer: systematic review and meta-analysis. Anticancer Res. 2012;32:3235–50.PubMed
18.
go back to reference Kountouri MP, Mammas IN, Spandidos DA. Human papilloma virus (HPV) in lung cancer: unanswered questions. Lung Cancer. 2010;67:125020.CrossRef Kountouri MP, Mammas IN, Spandidos DA. Human papilloma virus (HPV) in lung cancer: unanswered questions. Lung Cancer. 2010;67:125020.CrossRef
19.
go back to reference Papadakis ED, Soulitzis N, Spandidos DA. Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes. Br J Cancer. 2002;87:1013–8.PubMedCentralPubMedCrossRef Papadakis ED, Soulitzis N, Spandidos DA. Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes. Br J Cancer. 2002;87:1013–8.PubMedCentralPubMedCrossRef
20.
go back to reference de Araujo M, De Marco L, Santos C, Rubira-Bullen I, Ronco G, Pennini I, et al. GP5+/6+ SYBR Green methodology for simultaneous screening and quantification of human papillomavirus. J Clin Virol. 2009;45:90–5.PubMedCrossRef de Araujo M, De Marco L, Santos C, Rubira-Bullen I, Ronco G, Pennini I, et al. GP5+/6+ SYBR Green methodology for simultaneous screening and quantification of human papillomavirus. J Clin Virol. 2009;45:90–5.PubMedCrossRef
21.
go back to reference Roberts CC, Swoyer R, Bryan JT, Taddeo FJ. Comparison of real-time multiplex human papillomavirus (HPV) PCR assays with the linear array HPV genotyping PCR assay and influence of DNA extraction method on HPV detection. J Clin Microbiol. 2011;49:1899–906.PubMedCentralPubMedCrossRef Roberts CC, Swoyer R, Bryan JT, Taddeo FJ. Comparison of real-time multiplex human papillomavirus (HPV) PCR assays with the linear array HPV genotyping PCR assay and influence of DNA extraction method on HPV detection. J Clin Microbiol. 2011;49:1899–906.PubMedCentralPubMedCrossRef
22.
go back to reference Viallet J, Minna JD. Dominant oncogenes and tumor suppressor genes in the pathogenesis of lung cancer. Am J Respir Cell Mol Biol. 1990;2:225–32.PubMedCrossRef Viallet J, Minna JD. Dominant oncogenes and tumor suppressor genes in the pathogenesis of lung cancer. Am J Respir Cell Mol Biol. 1990;2:225–32.PubMedCrossRef
23.
go back to reference Lasithiotaki I, Antoniou KM, Derdas SP, Sarchianaki E, Symvoulakis EK, Psaraki A, et al. The presence of Merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl-2 genes in non-small cell lung cancer. Int J Cancer. 2013;133:604–11.PubMedCrossRef Lasithiotaki I, Antoniou KM, Derdas SP, Sarchianaki E, Symvoulakis EK, Psaraki A, et al. The presence of Merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl-2 genes in non-small cell lung cancer. Int J Cancer. 2013;133:604–11.PubMedCrossRef
24.
go back to reference Antoniou KM, Lasithiotaki I, Symvoulakis E, Derdas SP, Psaraki A, Spandidos DA, et al. Molecular pathological findings of Merkel cell polyomavirus in lung cancer: a possible etiopathogenetic link? Int J Cancer. 2013;133(12):3016–7. doi:10.1002/ijc.28308.PubMed Antoniou KM, Lasithiotaki I, Symvoulakis E, Derdas SP, Psaraki A, Spandidos DA, et al. Molecular pathological findings of Merkel cell polyomavirus in lung cancer: a possible etiopathogenetic link? Int J Cancer. 2013;133(12):3016–7. doi:10.​1002/​ijc.​28308.PubMed
25.
go back to reference Park MS, Chang YS, Shin JH, Kim DJ, Chung KY, Shin DH, et al. The prevalence of human papillomavirus infection in Korean non-small cell lung cancer patients. Yonsei Med J. 2007;48:69–77.PubMedCentralPubMedCrossRef Park MS, Chang YS, Shin JH, Kim DJ, Chung KY, Shin DH, et al. The prevalence of human papillomavirus infection in Korean non-small cell lung cancer patients. Yonsei Med J. 2007;48:69–77.PubMedCentralPubMedCrossRef
26.
go back to reference Fei Y, Yang J, Hsieh WC, Wu JY, Wu TC, Goan YG, et al. Different human papillomavirus 16/18 infection in Chinese non-small cell lung cancer patients living in Wuhan, China. Jpn J Clin Oncol. 2006;36:274–9.PubMedCrossRef Fei Y, Yang J, Hsieh WC, Wu JY, Wu TC, Goan YG, et al. Different human papillomavirus 16/18 infection in Chinese non-small cell lung cancer patients living in Wuhan, China. Jpn J Clin Oncol. 2006;36:274–9.PubMedCrossRef
27.
go back to reference Cheng YW, Wu MF, Wang J, Yeh KT, Goan YG, Chiou HL, et al. Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation. Cancer Res. 2007;67:10686–93.PubMedCrossRef Cheng YW, Wu MF, Wang J, Yeh KT, Goan YG, Chiou HL, et al. Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation. Cancer Res. 2007;67:10686–93.PubMedCrossRef
28.
go back to reference Tung MC, Wu HH, Cheng YW, Wang L, Chen CY, Yeh SD, et al. Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer. Cancer. 2013;119(18):3367–76. doi:10.1002/cncr.28220.PubMedCrossRef Tung MC, Wu HH, Cheng YW, Wang L, Chen CY, Yeh SD, et al. Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer. Cancer. 2013;119(18):3367–76. doi:10.​1002/​cncr.​28220.PubMedCrossRef
29.
go back to reference Wang JL, Fang CL, Wang M, Yu MC, Bai KJ, Lu PC, et al. Human papillomavirus infections as a marker to predict overall survival in lung adenocarcinoma. Int J Cancer. 2013. doi:10.1002/ijc.28349. Wang JL, Fang CL, Wang M, Yu MC, Bai KJ, Lu PC, et al. Human papillomavirus infections as a marker to predict overall survival in lung adenocarcinoma. Int J Cancer. 2013. doi:10.​1002/​ijc.​28349.
30.
go back to reference Hirayasu T, Iwamasa T, Kamada Y, Koyanagi Y, Usuda H, Genka K. Human papillomavirus DNA in squamous cell carcinoma of the lung. J Clin Pathol. 1996;49:810–7.PubMedCentralPubMedCrossRef Hirayasu T, Iwamasa T, Kamada Y, Koyanagi Y, Usuda H, Genka K. Human papillomavirus DNA in squamous cell carcinoma of the lung. J Clin Pathol. 1996;49:810–7.PubMedCentralPubMedCrossRef
31.
go back to reference Yu Y, Yang A, Hu S, Yan H. Correlation of HPV-16/18 infection of human papillomavirus with lung squamous cell carcinomas in Western China. Oncol Rep. 2009;21:1627–32.PubMed Yu Y, Yang A, Hu S, Yan H. Correlation of HPV-16/18 infection of human papillomavirus with lung squamous cell carcinomas in Western China. Oncol Rep. 2009;21:1627–32.PubMed
32.
go back to reference Wang Y, Wang A, Jiang R, Pan H, Huang B, Lu Y, et al. Human papillomavirus type 16 and 18 infection is associated with lung cancer patients from the central part of China. Oncol Rep. 2008;20:333–9.PubMed Wang Y, Wang A, Jiang R, Pan H, Huang B, Lu Y, et al. Human papillomavirus type 16 and 18 infection is associated with lung cancer patients from the central part of China. Oncol Rep. 2008;20:333–9.PubMed
33.
go back to reference Goto A, Li CP, Ota S, Niki T, Ohtsuki Y, Kitajima S, et al. Human papillomavirus infection in lung and esophageal cancers: analysis of 485 Asian cases. J Med Virol. 2011;83:1383–90.PubMedCrossRef Goto A, Li CP, Ota S, Niki T, Ohtsuki Y, Kitajima S, et al. Human papillomavirus infection in lung and esophageal cancers: analysis of 485 Asian cases. J Med Virol. 2011;83:1383–90.PubMedCrossRef
34.
go back to reference Chen SP, Hsu NY, Wu JY, Chen CY, Chou MC, Lee H, et al. Association of p53 codon 72 genotypes and clinical outcome in human papillomavirus-infected lung cancer patients. Ann Thorac Surg. 2013;95:1196–203.PubMedCrossRef Chen SP, Hsu NY, Wu JY, Chen CY, Chou MC, Lee H, et al. Association of p53 codon 72 genotypes and clinical outcome in human papillomavirus-infected lung cancer patients. Ann Thorac Surg. 2013;95:1196–203.PubMedCrossRef
35.
go back to reference Tung MC, Wu HH, Cheng YW, Wang L, Chen CY, Yeh SD, et al. Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer. Cancer. 2013;119:3367–76.PubMedCrossRef Tung MC, Wu HH, Cheng YW, Wang L, Chen CY, Yeh SD, et al. Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer. Cancer. 2013;119:3367–76.PubMedCrossRef
36.
go back to reference Cheng Y, Chiou H, Sheu GT, Hsieh LL, Chen CY, Su JM, et al. The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res. 2001;61:2799–803.PubMed Cheng Y, Chiou H, Sheu GT, Hsieh LL, Chen CY, Su JM, et al. The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res. 2001;61:2799–803.PubMed
37.
go back to reference Chiou HL, Wu MF, Liaw YC, Cheng YW, Wong RH, Chen CY, et al. The presence of human papillomavirus type 16/18 DNA in blood circulation may act as a risk marker of lung cancer in Taiwan. Cancer. 2003;97:1558–63.PubMedCrossRef Chiou HL, Wu MF, Liaw YC, Cheng YW, Wong RH, Chen CY, et al. The presence of human papillomavirus type 16/18 DNA in blood circulation may act as a risk marker of lung cancer in Taiwan. Cancer. 2003;97:1558–63.PubMedCrossRef
38.
go back to reference Cheng YW, Chiou HL, Chen JT, Chou MC, Lin TS, Lai WW, et al. Gender difference in human papillomavirus infection for non-small cell lung cancer in Taiwan. Lung Cancer. 2004;46:165–70.PubMedCrossRef Cheng YW, Chiou HL, Chen JT, Chou MC, Lin TS, Lai WW, et al. Gender difference in human papillomavirus infection for non-small cell lung cancer in Taiwan. Lung Cancer. 2004;46:165–70.PubMedCrossRef
39.
go back to reference Kato T, Koriyama C, Khan N, Samukawa T, Yanagi M, Hamada T, et al. EGFR mutations and human papillomavirus in lung cancer. Lung Cancer. 2012;78:144–7.PubMedCrossRef Kato T, Koriyama C, Khan N, Samukawa T, Yanagi M, Hamada T, et al. EGFR mutations and human papillomavirus in lung cancer. Lung Cancer. 2012;78:144–7.PubMedCrossRef
40.
go back to reference Baba M, Castillo A, Koriyama C, Yanagi M, Matsumoto H, Natsugoe S, et al. Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas. Oncol Rep. 2010;23:1085–92.PubMed Baba M, Castillo A, Koriyama C, Yanagi M, Matsumoto H, Natsugoe S, et al. Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas. Oncol Rep. 2010;23:1085–92.PubMed
41.
go back to reference Carpagnano GE, Koutelou A, Natalicchio MI, Martinelli D, Ruggieri C, Di Taranto A, et al. HPV in exhaled breath condensate of lung cancer patients. Br J Cancer. 2011;105:1183–90.PubMedCentralPubMedCrossRef Carpagnano GE, Koutelou A, Natalicchio MI, Martinelli D, Ruggieri C, Di Taranto A, et al. HPV in exhaled breath condensate of lung cancer patients. Br J Cancer. 2011;105:1183–90.PubMedCentralPubMedCrossRef
42.
go back to reference Lee SH, Vigliotti VS, Vigliotti JS, Pappu S. Routine human papillomavirus genotyping by DNA sequencing in community hospital laboratories. Infect Agent Cancer. 2007;2:1–11.CrossRef Lee SH, Vigliotti VS, Vigliotti JS, Pappu S. Routine human papillomavirus genotyping by DNA sequencing in community hospital laboratories. Infect Agent Cancer. 2007;2:1–11.CrossRef
Metadata
Title
Detection and genotype analysis of human papillomavirus in non-small cell lung cancer patients
Authors
Emmanouela Sarchianaki
Stavros P. Derdas
Markos Ntaoukakis
Elena Vakonaki
Eleni D. Lagoudaki
Ismini Lasithiotaki
Anna Sarchianaki
Anastasios Koutsopoulos
Emmanouil K. Symvoulakis
Demetrios A. Spandidos
Katerina M. Antoniou
George Sourvinos
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1419-2

Other articles of this Issue 4/2014

Tumor Biology 4/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine