Epigenetic Mechanisms of Human Papillomavirus–Associated Head and Neck Cancer

Archives of Pathology and Laboratory Medicine - Tập 139 Số 11 - Trang 1373-1378 - 2015
Nicole Anayannis, Nicolas F. Schlecht, Thomas J. Belbin1
1From the Departments of Pathology (Ms Anayannis and Dr Belbin), Epidemiology & Population Health (Dr Schlecht), and Medicine (Oncology) (Dr Schlecht), Albert Einstein College of Medicine, Bronx, New York.

Tóm tắt

Context Growing evidence suggests that as many as half of all oropharyngeal squamous cell carcinomas (OPSCCs) harbor human papillomavirus (HPV) infections. Despite being more advanced at diagnosis, HPV-positive OPSCCs are associated with a better response to therapy and longer patient survival than HPV-negative OPSCCs. Human papillomavirus–positive OPSCC has also been shown to have distinct host gene expression profiles compared with HPV-negative OPSCC. Recently, this distinction has been shown to include the epigenome. It is well supported that cancers are epigenetically deregulated. This review highlights epigenetic differences between HPV-positive and HPV-negative OPSCCs. The epigenetic mechanisms highlighted include methylation changes to host and viral DNA, and host chromatin modification. We also review the current evidence regarding host DNA methylation changes associated with smoking, and deregulation of microRNA expression in HPV-positive OPSCC. Objective To provide an overview of epigenetic mechanisms reported in HPV-positive OPSCC, with analogies to cervical cancer, and discussion of the challenges involved in studying epigenetic changes in HPV-associated OPSCC in combination with changes associated with smoking. Data Sources Sources were a literature review of peer-reviewed articles in PubMed on HPV and either OPSCC or head and neck squamous cell carcinoma, and related epigenetic mechanisms. Conclusions Epigenetic changes are reported to be a contributing factor to maintaining a malignant phenotype in HPV-positive OPSCC. The epigenetic mechanisms highlighted in this review can be studied for potential as biomarkers or as drug targets. Furthermore, continued research on the deregulation of epigenetic mechanisms in HPV-positive OPSCC (compared with HPV-negative OPSCC) may contribute to our understanding of the clinical and biologic differences between HPV-positive and HPV-negative OPSCC.

Từ khóa


Tài liệu tham khảo

Friedman, 2014, Clinical and scientific impact of human papillomavirus on head and neck cancer, World J Clin Oncol, 5, 781, 10.5306/wjco.v5.i4.781

Gillison, 2001, Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers, Curr Opin Oncol, 13, 183, 10.1097/00001622-200105000-00009

Smith, 2008, P16INK4a expression, human papillomavirus, and survival in head and neck cancer, Oral Oncol, 44, 133, 10.1016/j.oraloncology.2007.01.010

Shaw, 2011, The increasing clinical relevance of human papillomavirus type 16 (HPV-16) infection in oropharyngeal cancer, Br J Oral Maxillofac Surg, 49, 423, 10.1016/j.bjoms.2010.06.023

Schlecht, 2007, Gene expression profiles in HPV-infected head and neck cancer, J Pathol, 213, 283, 10.1002/path.2227

Slebos, 2006, Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma, Clin Cancer Res, 12, 701, 10.1158/1078-0432.CCR-05-2017

Lleras, 2013, Unique DNA methylation loci distinguish anatomic site and HPV status in head and neck squamous cell carcinoma, Clin Cancer Res, 19, 5444, 10.1158/1078-0432.CCR-12-3280

Maruya, 2004, Differential methylation status of tumor-associated genes in head and neck squamous carcinoma: incidence and potential implications, Clin Cancer Res, 10, 3825, 10.1158/1078-0432.CCR-03-0370

Noorlag, 2014, Promoter hypermethylation using 24-gene array in early head and neck cancer: better outcome in oral than in oropharyngeal cancer, Epigenetics, 9, 1220, 10.4161/epi.29785

Zuo, 2004, O6-methylguanine-DNA methyltransferase gene: epigenetic silencing and prognostic value in head and neck squamous cell carcinoma, Cancer Epidemiol, 13, 967

Parfenov, 2014, Characterization of HPV and host genome interactions in primary head and neck cancers, Proc Natl Acad Sci U S A, 111, 15544, 10.1073/pnas.1416074111

Sartor, 2011, Genome-wide methylation and expression differences in HPV(+) and HPV(-) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis, Epigenetics, 6, 777, 10.4161/epi.6.6.16216

Schlecht, Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV positive oropharyngeal squamous cell carcinoma [published online ahead of print January 26, 2015], Cancer Med, 10.1002/cam4.374

van Kempen, 2014, Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: a systematic review, Epigenetics, 9, 194, 10.4161/epi.26881

Kostareli, 2013, HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas, J Clin Invest, 123, 2488, 10.1172/JCI67010

Wilson, 2013, Integrated virus-host methylome analysis in head and neck squamous cell carcinoma, Epigenetics, 8, 953, 10.4161/epi.25614

Sawada, 2007, Increased expression of DNA methyltransferase 1 (DNMT1) protein in uterine cervix squamous cell carcinoma and its precursor lesion, Cancer Lett, 251, 211, 10.1016/j.canlet.2006.11.023

Burgers, 2007, Viral oncoproteins target the DNA methyltransferases, Oncogene, 26, 1650, 10.1038/sj.onc.1209950

Koutsodontis, 2001, Sp1 plays a critical role in the transcriptional activation of the human cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene by the p53 tumor suppressor protein, J Biol Chem, 276, 29116, 10.1074/jbc.M104130200

Kimura, 2003, Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways, Nucleic Acids Res, 31, 3101, 10.1093/nar/gkg406

Zeilinger, 2013, Tobacco smoking leads to extensive genome-wide changes in DNA methylation, PloS One, 8, 10.1371/journal.pone.0063812

Breitling, 2011, Tobacco-smoking-related differential DNA methylation: 27K discovery and replication, Am J Hum Genet, 88, 450, 10.1016/j.ajhg.2011.03.003

Shigaki, 2012, LINE-1 hypomethylation in noncancerous esophageal mucosae is associated with smoking history, Ann Surg Oncol, 19, 4238, 10.1245/s10434-012-2488-y

Searles Nielsen, 2012, LINE-1 DNA methylation, smoking and risk of Parkinson's disease, J Parkinsons Dis, 2, 303, 10.3233/JPD-012129

Lee, 1993, Cigarette smoking, nicotine addiction, and its pharmacologic treatment, Arch Intern Med, 153, 34, 10.1001/archinte.1993.00410010062005

Piyathilake, 2000, Localized folate and vitamin B-12 deficiency in squamous cell lung cancer is associated with global DNA hypomethylation, Nutr Cancer, 37, 99, 10.1207/S15327914NC3701_13

Piyathilake, 2000, The accumulation of ascorbic acid by squamous cell carcinomas of the lung and larynx is associated with global methylation of DNA, Cancer, 89, 171, 10.1002/1097-0142(20000701)89:1<171::AID-CNCR22>3.0.CO;2-O

Ross, 2003, Diet and DNA methylation interactions in cancer prevention, Ann N Y Acad Sci, 983, 197, 10.1111/j.1749-6632.2003.tb05974.x

Gabriel, 2006, Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults, Am J Clin Nutr, 83, 835, 10.1093/ajcn/83.4.835

Liu, 2011, Hypoxia induces genomic DNA demethylation through the activation of HIF-1alpha and transcriptional upregulation of MAT2A in hepatoma cells, Mol Cancer Ther, 10, 1113, 10.1158/1535-7163.MCT-10-1010

Breton, 2009, Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation, Am J Respir Crit Care Med, 180, 462, 10.1164/rccm.200901-0135OC

Demokan, 2011, Role of DNA methylation in head and neck cancer, Clin Epigenet, 2, 123, 10.1007/s13148-011-0045-3

Arantes, 2014, Methylation as a biomarker for head and neck cancer, Oral Oncol, 50, 587, 10.1016/j.oraloncology.2014.02.015

Gasche, 2012, Epigenetic mechanisms in oral carcinogenesis, Future Oncol, 8, 1407, 10.2217/fon.12.138

Rosas, 2001, Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients, Cancer Res, 61, 939

Zochbauer-Muller, 2003, Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers, Int J Cancer, 107, 612, 10.1002/ijc.11458

Jarmalaite, 2003, Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer, Int J Cancer, 106, 913, 10.1002/ijc.11322

Belinsky, 2002, Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers, Cancer Res, 62, 2370

Esteller, 2001, A gene hypermethylation profile of human cancer, Cancer Res, 61, 3225

Bearzatto, 2002, p16(INK4A) Hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer, Clin Cancer Res, 8, 3782

Kashiwabara, 1998, Correlation between methylation status of the p16/CDKN2 gene and the expression of p16 and Rb proteins in primary non-small cell lung cancers, Int J Cancer, 79, 215, 10.1002/(SICI)1097-0215(19980619)79:3<215::AID-IJC1>3.0.CO;2-S

Seike, 2000, Increase in the frequency of p16INK4 gene inactivation by hypermethylation in lung cancer during the process of metastasis and its relation to the status of p53, Clin Cancer Res, 6, 4307

Farias, 2010, Effect of age on the association between p16CDKN2A methylation and DNMT3B polymorphism in head and neck carcinoma and patient survival, Int J Oncol, 37, 167

Steinmann, 2009, Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma, Oncol Rep, 22, 1519

Ha, 2006, Promoter methylation and inactivation of tumour-suppressor genes in oral squamous-cell carcinoma, Lancet Oncol, 7, 77, 10.1016/S1470-2045(05)70540-4

Shaw, 2006, Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing, Br J Cancer, 94, 561, 10.1038/sj.bjc.6602972

Esteller, 1999, Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients, Cancer Res, 59, 67

Mishra, 2009, Cyclin D1 expression and its possible regulation in chewing tobacco mediated oral squamous cell carcinoma progression, Arch Oral Biol, 54, 917, 10.1016/j.archoralbio.2009.07.003

Petty, 2003, Cyclin D1 as a target for chemoprevention, Lung Cancer, 41, S155, 10.1016/S0169-5002(03)00159-4

Zochbauer-Muller, 2001, Aberrant promoter methylation of multiple genes in non-small cell lung cancers, Cancer Res, 61, 249

Virmani, 2000, Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas, J Natl Cancer Inst, 92, 1303, 10.1093/jnci/92.16.1303

Ostrow, 2010, Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR, Clin Cancer Res, 16, 3463, 10.1158/1078-0432.CCR-09-3304

Chen, 2007, Methylation of multiple genes as diagnostic and therapeutic markers in primary head and neck squamous cell carcinoma, Arch Otolaryngol Head Neck Surg, 133, 1131, 10.1001/archotol.133.11.1131

Burbee, 2001, Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression, J Natl Cancer Inst, 93, 691, 10.1093/jnci/93.9.691

Kwok, 2009, Role of the RARRES1 gene in nasopharyngeal carcinoma, Cancer Genet Cytogenet, 194, 58, 10.1016/j.cancergencyto.2009.06.005

Palmisano, 2000, Predicting lung cancer by detecting aberrant promoter methylation in sputum, Cancer Res, 60, 5954

Zhang, 2006, Promoter hypermethylation of DNA repair gene MGMT in laryngeal squamous cell carcinoma, J Huazhong Univ Sci Technolog Med Sci, 26, 101, 10.1007/BF02828051

De Jong, 2009, Promoter methylation primarily occurs in tumor cells of patients with non-small cell lung cancer, Anticancer Res, 29, 363

Guo, 2006, Hypermethylation of the GATA gene family in esophageal cancer, Int J Cancer, 119, 2078, 10.1002/ijc.22092

Guo, 2004, Hypermethylation of the GATA genes in lung cancer, Clin Cancer Res, 10, 7917, 10.1158/1078-0432.CCR-04-1140

Liu, 2012, DAPK promoter hypermethylation in tissues and body fluids of oral precancer patients, Med Oncol, 29, 729, 10.1007/s12032-011-9953-5

Zochbauer-Muller, 2001, 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer, Cancer Res, 61, 3581

Sundar, 2011, Lung cancer and its association with chronic obstructive pulmonary disease: update on nexus of epigenetics, Curr Opin Pulm Med, 17, 279, 10.1097/MCP.0b013e3283477533

Subbalekha, 2009, Detection of LINE-1s hypomethylation in oral rinses of oral squamous cell carcinoma patients, Oral Oncol, 45, 184, 10.1016/j.oraloncology.2008.05.002

Guerrero-Preston, 2009, Global DNA methylation: a common early event in oral cancer cases with exposure to environmental carcinogens or viral agents, P R Health Sci J, 28, 24

Phokaew, 2008, LINE-1 methylation patterns of different loci in normal and cancerous cells, Nucleic Acids Res, 36, 5704, 10.1093/nar/gkn571

Terry, 2011, DNA methylation in white blood cells: association with risk factors in epidemiologic studies, Epigenetics, 6, 828, 10.4161/epi.6.7.16500

Baylin, 2011, A decade of exploring the cancer epigenome - biological and translational implications, Nat Rev Cancer, 11, 726, 10.1038/nrc3130

Holland, 2008, Activation of the enhancer of zeste homologue 2 gene by the human papillomavirus E7 oncoprotein, Cancer Res, 68, 9964, 10.1158/0008-5472.CAN-08-1134

McCabe, 2009, Cancer DNA methylation: molecular mechanisms and clinical implications, Clin Cancer Res, 15, 3927, 10.1158/1078-0432.CCR-08-2784

Biron, 2012, Alan Underhill D, Seikaly H. Epigenetic differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas, J Otolaryngol Head Neck Surg, 41, S65

Duenas-Gonzalez, 2005, Epigenetics of cervical cancer: an overview and therapeutic perspectives, Mol Cancer, 4, 38, 10.1186/1476-4598-4-38

Verma, 2003, Viral genes and methylation, Ann N Y Acad Sci, 983, 170, 10.1111/j.1749-6632.2003.tb05972.x

Tao, 2002, Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells, Hum Mol Genet, 11, 2091, 10.1093/hmg/11.18.2091

Tao, 2003, Stealth technology: how Epstein-Barr virus utilizes DNA methylation to cloak itself from immune detection, Clin Immunol. Oct, 109, 53, 10.1016/S1521-6616(03)00198-0

Rosl, 1993, zur Hausen H. The effect of DNA methylation on gene regulation of human papillomaviruses, J Gen Virol, 74, 791, 10.1099/0022-1317-74-5-791

Badal, 2003, CpG methylation of human papillomavirus type 16 DNA in cervical cancer cell lines and in clinical specimens: genomic hypomethylation correlates with carcinogenic progression, J Virol, 77, 6227, 10.1128/JVI.77.11.6227-6234.2003

Castle, 2005, Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities, J Natl Cancer Inst, 97, 1066, 10.1093/jnci/dji186

Khan, 2005, The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice, J Natl Cancer Inst, 97, 1072, 10.1093/jnci/dji187

Clifford, 2003, Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis, Br J Cancer, 88, 63, 10.1038/sj.bjc.6600688

Bosch, 2003, Chapter 1: human papillomavirus and cervical cancer–burden and assessment of causality, J Natl Cancer Inst Monogr, 3, 10.1093/oxfordjournals.jncimonographs.a003479

Nuovo, 1999, In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis, Proc Natl Acad Sci U S A, 96, 12754, 10.1073/pnas.96.22.12754

Brebi, 2014, Evaluation of ZAR1 and SFRP4 methylation status as potentials biomarkers for diagnosis in cervical cancer: exploratory study phase I, Biomarkers, 19, 181, 10.3109/1354750X.2013.867535

Lea, 2004, Aberrant p16 methylation is a biomarker for tobacco exposure in cervical squamous cell carcinogenesis, Am J Obstet Gynecol, 190, 674, 10.1016/j.ajog.2003.09.036

Brebi, 2014, Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population, Epigenetics, 9, 308, 10.4161/epi.27120

Feng, 2005, Detection of hypermethylated genes in women with and without cervical neoplasia, J Natl Cancer Inst, 97, 273, 10.1093/jnci/dji041

Kang, 2006, Methylation of p16INK4a is a non-rare event in cervical intraepithelial neoplasia, Diagn Mol Pathol, 15, 74, 10.1097/00019606-200606000-00003

Nehls, 2008, p16 methylation does not affect protein expression in cervical carcinogenesis, Eur J Cancer, 44, 2496, 10.1016/j.ejca.2008.07.014

Wentzensen, 2009, Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science, Gynecol Oncol, 112, 293, 10.1016/j.ygyno.2008.10.012

Wang, 2008, Identification of novel methylation markers in cervical cancer using restriction landmark genomic scanning, Cancer Res, 68, 2489, 10.1158/0008-5472.CAN-07-3194

Virmani, 2001, Aberrant methylation during cervical carcinogenesis, Clin Cancer Res, 7, 584

Dong, 2001, Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix, Clin Cancer Res, 7, 1982

Narayan, 2003, Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome, Mol Cancer, 2, 24, 10.1186/1476-4598-2-24

Martin, 2006, Molecular profiling of cervical neoplasia, Expert Rev Mol Diagn, 6, 217, 10.1586/14737159.6.2.217

Lu, 2005, MicroRNA expression profiles classify human cancers, Nature, 435, 834, 10.1038/nature03702

Sassen, 2008, MicroRNA: implications for cancer, Virchows Arch, 452, 1, 10.1007/s00428-007-0532-2

Hui, 2010, Comprehensive microRNA profiling for head and neck squamous cell carcinomas, Clin Cancer Res, 16, 1129, 10.1158/1078-0432.CCR-09-2166

Childs, 2009, Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma, Am J Pathol, 174, 736, 10.2353/ajpath.2009.080731

Harris, 2012, Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and neck squamous cell carcinomas, Am J Pathol, 180, 917, 10.1016/j.ajpath.2011.12.004

Jimenez, MicroRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma, Arch Pathol Lab Med, 139, 1349, 10.5858/arpa.2014-0471-OA

Lajer, 2012, The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer, Br J Cancer, 106, 1526, 10.1038/bjc.2012.109

Zheng, 2011, Regulation of cellular miRNA expression by human papillomaviruses, Biochim Biophys Acta, 1809, 668, 10.1016/j.bbagrm.2011.05.005

Fernandez, 2010, Viral epigenomes in human tumorigenesis, Oncogene, 29, 1405, 10.1038/onc.2009.517

Sun, 2011, Methylation of HPV16 genome CpG sites is associated with cervix precancer and cancer, Gynecol Oncol, 121, 59, 10.1016/j.ygyno.2011.01.013

Mirabello, 2013, Elevated methylation of HPV16 DNA is associated with the development of high grade cervical intraepithelial neoplasia, Int J Cancer, 132, 1412, 10.1002/ijc.27750

Schiffman, 2007, Human papillomavirus and cervical cancer, Lancet, 370, 890, 10.1016/S0140-6736(07)61416-0

Park, 2011, Characterization of the methylation patterns in human papillomavirus type 16 viral DNA in head and neck cancers, Cancer Prev Res (Phila), 4, 207, 10.1158/1940-6207.CAPR-10-0147

Balderas-Loaeza, 2007, Human papillomavirus-16 DNA methylation patterns support a causal association of the virus with oral squamous cell carcinomas, Int J Cancer, 120, 2165, 10.1002/ijc.22563

Stunkel, 1999, The chromatin structure of the long control region of human papillomavirus type 16 represses viral oncoprotein expression, J Virol, 73, 1918, 10.1128/JVI.73.3.1918-1930.1999

Romanczuk, 1991, The viral transcriptional regulatory region upstream of the E6 and E7 genes is a major determinant of the differential immortalization activities of human papillomavirus types 16 and 18, J Virol, 65, 2739, 10.1128/JVI.65.5.2739-2744.1991