Skip to main content
SpringerLink
Log in

Molecular Patterns and Biology of HPV-Associated HNSCC

  • Chapter
  • First Online:
HPV Infection in Head and Neck Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 206))

Abstract

Head and neck cancer is the sixth most common cancer worldwide. The large majority are squamous cell carcinomas (HNSCC) that develop in the mucosal linings of the upper aerodigestive tract. These tumors develop either by exogenous carcinogen exposure (smoking, alcohol drinking) or by human papillomavirus (HPV) infection, particularly those in the oropharynx (OPSCC). HPV-positive (HPV+ve) and HPV-negative (HPV-ve) OPSCC are considered different disease entities. HPV+ve tumors are different at the molecular level and likely as a consequence have a much more favorable prognosis than HPV-ve tumors, despite their generally advanced stage at presentation. In general, HNSCCs develop in precancerous mucosal changes, and the apparent lack of precancerous HPV+ve mucosal changes is therefore remarkable. In this Chapter, head and neck carcinogenesis is discussed and the molecular differences between HPV+ve and HPV-ve tumors are outlined.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Balz V, Scheckenbach K, Gotte K, Bockmuhl U, Petersen I, Bier H (2003) Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2-11 and human papillomavirus 16/18 E6 transcripts in 123 unselected tumor specimens. Cancer Res 63(6):1188–1191

    CAS  PubMed  Google Scholar 

  • Bayo P, Jou A, Stenzinger A, Shao C, Gross M, Jensen A, Grabe N, Mende CH, Rados PV, Debus J, Weichert W, Plinkert PK, Lichter P, Freier K, Hess J (2015) Loss of SOX2 expression induces cell motility via vimentin up-regulation and is an unfavorable risk factor for survival of head and neck squamous cell carcinoma. Mol Oncol 9(8):1704–1719. doi:10.1016/j.molonc.2015.05.006

    Article  CAS  PubMed  Google Scholar 

  • Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, Kerkhoven RM, Madiredjo M, Nijkamp W, Weigelt B, Agami R, Ge W, Cavet G, Linsley PS, Beijersbergen RL, Bernards R (2004) A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428(6981):431–437. doi:10.1038/nature02371

    Article  CAS  PubMed  Google Scholar 

  • Braakhuis BJ, Snijders PJ, Keune WJ, Meijer CJ, Ruijter-Schippers HJ, Leemans CR, Brakenhoff RH (2004) Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst 96(13):998–1006

    Article  CAS  PubMed  Google Scholar 

  • Brcic L, Sherer CK, Shuai Y, Hornick JL, Chirieac LR, Dacic S (2012) Morphologic and clinicopathologic features of lung squamous cell carcinomas expressing Sox2. Am J Clin Pathol 138(5):712–718. doi:10.1309/AJCP05TTWQTWNLTN

    Article  PubMed  Google Scholar 

  • Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, Corio R, Lee D, Greenberg B, Koch W, Sidransky D (1996) Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 56(11):2488–2492

    CAS  PubMed  Google Scholar 

  • Cancer Genome Atlas N (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517(7536):576–582. doi:10.1038/nature14129

    Article  Google Scholar 

  • Chou CH, Chang NW, Shrestha S, Hsu SD, Lin YL, Lee WH, Yang CD, Hong HC, Wei TY, Tu SJ, Tsai TR, Ho SY, Jian TY, Wu HY, Chen PR, Lin NC, Huang HT, Yang TL, Pai CY, Tai CS, Chen WL, Huang CY, Liu CC, Weng SL, Liao KW, Hsu WL, Huang HD (2016) miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res 44(D1):D239–D247. doi:10.1093/nar/gkv1258

    Article  PubMed  Google Scholar 

  • Chung CH, Parker JS, Karaca G, Wu J, Funkhouser WK, Moore D, Butterfoss D, Xiang D, Zanation A, Yin X, Shockley WW, Weissler MC, Dressler LG, Shores CG, Yarbrough WG, Perou CM (2004) Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell 5(5):489–500

    Article  CAS  PubMed  Google Scholar 

  • Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA, Louis DN, Li FP, Rheinwald JG (2000) Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol Cell Biol 20(4):1436–1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao G, Gay HA, Chernock RD, Zhang TR, Luo J, Thorstad WL, Lewis JS Jr, Wang X (2013) A microRNA expression signature for the prognosis of oropharyngeal squamous cell carcinoma. Cancer 119(1):72–80. doi:10.1002/cncr.27696

    Article  CAS  PubMed  Google Scholar 

  • Gerner EW, Meyskens FL Jr (2004) Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 4(10):781–792. doi:10.1038/nrc1454

    Article  CAS  PubMed  Google Scholar 

  • Gu W, An J, Ye P, Zhao KN, Antonsson A (2011) Prediction of conserved microRNAs from skin and mucosal human papillomaviruses. Arch Virol 156(7):1161–1171. doi:10.1007/s00705-011-0974-3

    Article  CAS  PubMed  Google Scholar 

  • Ha PK, Califano JA (2004) The role of human papillomavirus in oral carcinogenesis. Crit Rev Oral Biol Med 15(4):188–196

    Article  PubMed  Google Scholar 

  • Hafkamp HC, Mooren JJ, Claessen SM, Klingenberg B, Voogd AC, Bot FJ, Klussmann JP, Hopman AH, Manni JJ, Kremer B, Ramaekers FC, Speel EJ (2009) P21 Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis. Mod Pathol 22(5):686–698. doi:10.1038/modpathol.2009.23

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  • Hanna E, Shrieve DC, Ratanatharathorn V, Xia X, Breau R, Suen J, Li S (2001) A novel alternative approach for prediction of radiation response of squamous cell carcinoma of head and neck. Cancer Res 61(6):2376–2380

    CAS  PubMed  Google Scholar 

  • Huebbers CU, Preuss SF, Kolligs J, Vent J, Stenner M, Wieland U, Silling S, Drebber U, Speel EJ, Klussmann JP (2013) Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis. PLoS ONE 8(2):e57207. doi:10.1371/journal.pone.0057207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung AC, Briolat J, Millon R, de Reynies A, Rickman D, Thomas E, Abecassis J, Clavel C, Wasylyk B (2010) Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma. Int J Cancer 126(8):1882–1894. doi:10.1002/ijc.24911

    CAS  PubMed  Google Scholar 

  • Keck MK, Zuo Z, Khattri A, Stricker TP, Brown CD, Imanguli M, Rieke D, Endhardt K, Fang P, Bragelmann J, DeBoer R, El-Dinali M, Aktolga S, Lei Z, Tan P, Rozen SG, Salgia R, Weichselbaum RR, Lingen MW, Story MD, Ang KK, Cohen EE, White KP, Vokes EE, Seiwert TY (2015) Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res 21(4):870–881. doi:10.1158/1078-0432.CCR-14-2481

    Article  CAS  PubMed  Google Scholar 

  • Klussmann JP, Gultekin E, Weissenborn SJ, Wieland U, Dries V, Dienes HP, Eckel HE, Pfister HJ, Fuchs PG (2003) Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol 162(3):747–753. doi:10.1016/S0002-9440(10)63871-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klussmann JP, Mooren JJ, Lehnen M, Claessen SM, Stenner M, Huebbers CU, Weissenborn SJ, Wedemeyer I, Preuss SF, Straetmans JM, Manni JJ, Hopman AH, Speel EJ (2009) Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res 15(5):1779–1786. doi:10.1158/1078-0432.CCR-08-1463

    Article  CAS  PubMed  Google Scholar 

  • Lajer CB, Nielsen FC, Friis-Hansen L, Norrild B, Borup R, Garnaes E, Rossing M, Specht L, Therkildsen MH, Nauntofte B, Dabelsteen S, von Buchwald C (2011) Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study. Br J Cancer 104(5):830–840. doi:10.1038/bjc.2011.29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lajer CB, Garnaes E, Friis-Hansen L, Norrild B, Therkildsen MH, Glud M, Rossing M, Lajer H, Svane D, Skotte L, Specht L, Buchwald C, Nielsen FC (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(9):1526–1534. doi:10.1038/bjc.2012.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    Article  CAS  PubMed  Google Scholar 

  • Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11(1):9–22. doi:10.1038/nrc2982

    Article  CAS  PubMed  Google Scholar 

  • Lim X, Tan SH, Koh WL, Chau RM, Yan KS, Kuo CJ, van Amerongen R, Klein AM, Nusse R (2013) Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling. Science 342(6163):1226–1230. doi:10.1126/science.1239730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lohavanichbutr P, Houck J, Fan W, Yueh B, Mendez E, Futran N, Doody DR, Upton MP, Farwell DG, Schwartz SM, Zhao LP, Chen C (2009) Genomewide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer: potential implications for treatment choices. Arch Otolaryngol Head Neck Surg 135(2):180–188. doi:10.1001/archoto.2008.540

    Article  PubMed  PubMed Central  Google Scholar 

  • Martinez I, Wang J, Hobson KF, Ferris RL, Khan SA (2007) Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer 43(2):415–432. doi:10.1016/j.ejca.2006.09.001

    Article  CAS  PubMed  Google Scholar 

  • Miller DL, Davis JW, Taylor KH, Johnson J, Shi Z, Williams R, Atasoy U, Lewis JS Jr, Stack MS (2015) Identification of a human papillomavirus-associated oncogenic miRNA panel in human oropharyngeal squamous cell carcinoma validated by bioinformatics analysis of the Cancer Genome Atlas. Am J Pathol 185(3):679–692. doi:10.1016/j.ajpath.2014.11.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mirghani H, Ugolin N, Ory C, Lefevre M, Baulande S, Hofman P, St Guily JL, Chevillard S, Lacave R (2014) A predictive transcriptomic signature of oropharyngeal cancer according to HPV16 status exclusively. Oral Oncol 50(11):1025–1034. doi:10.1016/j.oraloncology.2014.07.019

    Article  CAS  PubMed  Google Scholar 

  • Mooren JJ, Gultekin SE, Straetmans JM, Haesevoets A, Peutz-Kootstra CJ, Huebbers CU, Dienes HP, Wieland U, Ramaekers FC, Kremer B, Speel EJ, Klussmann JP (2014) P16(INK4A) immunostaining is a strong indicator for high-risk-HPV-associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low-risk-HPV-infection in head and neck papillomas and laryngeal dysplasias. Int J Cancer 134(9):2108–2117. doi:10.1002/ijc.28534

    Article  CAS  PubMed  Google Scholar 

  • Napier SS, Speight PM (2008) Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med 37(1):1–10. doi:10.1111/j.1600-0714.2007.00579.x

    Article  PubMed  Google Scholar 

  • Opitz OG, Suliman Y, Hahn WC, Harada H, Blum HE, Rustgi AK (2001) Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism. J Clin Invest 108(5):725–732. doi:10.1172/JCI11909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA, Ridge JA, Goodwin J, Kenady D, Saunders J, Westra W, Sidransky D, Koch WM (2007) TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med 357(25):2552–2561. doi:10.1056/NEJMoa073770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Preuss SF, Weinell A, Molitor M, Semrau R, Stenner M, Drebber U, Wedemeyer I, Hoffmann TK, Guntinas-Lichius O, Klussmann JP (2008a) Survivin and epidermal growth factor receptor expression in surgically treated oropharyngeal squamous cell carcinoma. Head Neck 30(10):1318–1324. doi:10.1002/hed.20876

    Article  PubMed  Google Scholar 

  • Preuss SF, Weinell A, Molitor M, Stenner M, Semrau R, Drebber U, Weissenborn SJ, Speel EJ, Wittekindt C, Guntinas-Lichius O, Hoffmann TK, Eslick GD, Klussmann JP (2008b) Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer. Br J Cancer 98(3):627–632. doi:10.1038/sj.bjc.6604192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prigge ES, Toth C, Dyckhoff G, Wagner S, Muller F, Wittekindt C, Freier K, Plinkert P, Hoffmann J, Vinokurova S, Klussmann JP, von Knebel Doeberitz M, Reuschenbach M (2015) p16(INK4a)/Ki-67 co-expression specifically identifies transformed cells in the head and neck region. Int J Cancer 136(7):1589–1599. doi:10.1002/ijc.29130

    Article  CAS  PubMed  Google Scholar 

  • Pyeon D, Newton MA, Lambert PF, den Boon JA, Sengupta S, Marsit CJ, Woodworth CD, Connor JP, Haugen TH, Smith EM, Kelsey KT, Turek LP, Ahlquist P (2007) Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers. Cancer Res 67(10):4605–4619. doi:10.1158/0008-5472.CAN-06-3619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian K, Pietila T, Ronty M, Michon F, Frilander MJ, Ritari J, Tarkkanen J, Paulin L, Auvinen P, Auvinen E (2013a) Identification and validation of human papillomavirus encoded microRNAs. PLoS ONE 8(7):e70202. doi:10.1371/journal.pone.0070202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian X, Wagner S, Ma C, Klussmann JP, Hummel M, Kaufmann AM, Albers AE (2013b) ALDH1-positive cancer stem-like cells are enriched in nodal metastases of oropharyngeal squamous cell carcinoma independent of HPV status. Oncol Rep 29(5):1777–1784. doi:10.3892/or.2013.2340

    CAS  PubMed  Google Scholar 

  • Qian X, Wagner S, Ma C, Coordes A, Gekeler J, Klussmann JP, Hummel M, Kaufmann AM, Albers AE (2014) Prognostic significance of ALDH1A1-positive cancer stem cells in patients with locally advanced, metastasized head and neck squamous cell carcinoma. J Cancer Res Clin Oncol 140(7):1151–1158. doi:10.1007/s00432-014-1685-4

    Article  CAS  PubMed  Google Scholar 

  • Reed AL, Califano J, Cairns P, Westra WH, Jones RM, Koch W, Ahrendt S, Eby Y, Sewell D, Nawroz H, Bartek J, Sidransky D (1996) High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res 56(16):3630–3633

    CAS  PubMed  Google Scholar 

  • Reimers N, Kasper HU, Weissenborn SJ, Stutzer H, Preuss SF, Hoffmann TK, Speel EJ, Dienes HP, Pfister HJ, Guntinas-Lichius O, Klussmann JP (2007) Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer 120(8):1731–1738. doi:10.1002/ijc.22355

    Article  CAS  PubMed  Google Scholar 

  • Rheinwald JG, Hahn WC, Ramsey MR, Wu JY, Guo Z, Tsao H, De Luca M, Catricala C, O’Toole KM (2002) A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. Mol Cell Biol 22(14):5157–5172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rietbergen MM, Braakhuis BJ, Moukhtari N, Bloemena E, Brink A, Sie D, Ylstra B, Baatenburg de Jong RJ, Snijders PJ, Brakenhoff RH, Leemans CR (2014) No evidence for active human papillomavirus (HPV) in fields surrounding HPV-positive oropharyngeal tumors. J Oral Pathol Med 43(2):137–142. doi:10.1111/jop.12123

    Article  CAS  PubMed  Google Scholar 

  • Schlecht NF, Burk RD, Adrien L, Dunne A, Kawachi N, Sarta C, Chen Q, Brandwein-Gensler M, Prystowsky MB, Childs G, Smith RV, Belbin TJ (2007) Gene expression profiles in HPV-infected head and neck cancer. J Pathol 213(3):283–293. doi:10.1002/path.2227

    Article  CAS  PubMed  Google Scholar 

  • Sewell A, Brown B, Biktasova A, Mills GB, Lu Y, Tyson DR, Issaeva N, Yarbrough WG (2014) Reverse-phase protein array profiling of oropharyngeal cancer and significance of PIK3CA mutations in HPV-associated head and neck cancer. Clin Cancer Res 20(9):2300–2311. doi:10.1158/1078-0432.CCR-13-2585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6(5):963–968

    Article  CAS  PubMed  Google Scholar 

  • Slebos RJ, Yi Y, Ely K, Carter J, Evjen A, Zhang X, Shyr Y, Murphy BM, Cmelak AJ, Burkey BB, Netterville JL, Levy S, Yarbrough WG, Chung CH (2006) Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma. Clin Cancer Res 12(3 Pt 1):701–709. doi:10.1158/1078-0432.CCR-05-2017

    Article  CAS  PubMed  Google Scholar 

  • Smeets SJ, Braakhuis BJ, Abbas S, Snijders PJ, Ylstra B, van de Wiel MA, Meijer GA, Leemans CR, Brakenhoff RH (2006) Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus. Oncogene 25(17):2558–2564. doi:10.1038/sj.onc.1209275

    Article  CAS  PubMed  Google Scholar 

  • Smeets SJ, Brakenhoff RH, Ylstra B, van Wieringen WN, van de Wiel MA, Leemans CR, Braakhuis BJ (2009) Genetic classification of oral and oropharyngeal carcinomas identifies subgroups with a different prognosis. Cell Oncol 31(4):291–300. doi:10.3233/CLO-2009-0471

    CAS  PubMed  PubMed Central  Google Scholar 

  • Smeets SJ, van der Plas M, Schaaij-Visser TB, van Veen EA, van Meerloo J, Braakhuis BJ, Steenbergen RD, Brakenhoff RH (2011) Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways. Int J Cancer 128(7):1596–1605. doi:10.1002/ijc.25474

    Article  CAS  PubMed  Google Scholar 

  • Snijders PJ, van Duin M, Walboomers JM, Steenbergen RD, Risse EK, Helmerhorst TJ, Verheijen RH, Meijer CJ (1998) Telomerase activity exclusively in cervical carcinomas and a subset of cervical intraepithelial neoplasia grade III lesions: strong association with elevated messenger RNA levels of its catalytic subunit and high-risk human papillomavirus DNA. Cancer Res 58(17):3812–3818

    CAS  PubMed  Google Scholar 

  • Tabor MP, Brakenhoff RH, van Houten VM, Kummer JA, Snel MH, Snijders PJ, Snow GB, Leemans CR, Braakhuis BJ (2001) Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7(6):1523–1532

    CAS  PubMed  Google Scholar 

  • van der Waal I (2009) Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 45(4–5):317–323. doi:10.1016/j.oraloncology.2008.05.016

    Article  PubMed  Google Scholar 

  • van Houten VM, Snijders PJ, van den Brekel MW, Kummer JA, Meijer CJ, van Leeuwen B, Denkers F, Smeele LE, Snow GB, Brakenhoff RH (2001) Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas. Int J Cancer 93(2):232–235. doi:10.1002/ijc.1313

    Article  PubMed  Google Scholar 

  • van Houten VM, Tabor MP, van den Brekel MW, Kummer JA, Denkers F, Dijkstra J, Leemans R, van der Waal I, Snow GB, Brakenhoff RH (2002) Mutated p53 as a molecular marker for the diagnosis of head and neck cancer. J Pathol 198(4):476–486. doi:10.1002/path.1242

    Article  PubMed  Google Scholar 

  • Wald AI, Hoskins EE, Wells SI, Ferris RL, Khan SA (2011) Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus. Head Neck 33(4):504–512. doi:10.1002/hed.21475

    Article  PubMed  PubMed Central  Google Scholar 

  • Walter V, Yin X, Wilkerson MD, Cabanski CR, Zhao N, Du Y, Ang MK, Hayward MC, Salazar AH, Hoadley KA, Fritchie K, Sailey CJ, Weissler MC, Shockley WW, Zanation AM, Hackman T, Thorne LB, Funkhouser WD, Muldrew KL, Olshan AF, Randell SH, Wright FA, Shores CG, Hayes DN (2013) Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes. PLoS ONE 8(2):e56823. doi:10.1371/journal.pone.0056823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitfield ML, George LK, Grant GD, Perou CM (2006) Common markers of proliferation. Nat Rev Cancer 6(2):99–106. doi:10.1038/nrc1802

    Article  CAS  PubMed  Google Scholar 

  • Wilkerson MD, Yin X, Hoadley KA, Liu Y, Hayward MC, Cabanski CR, Muldrew K, Miller CR, Randell SH, Socinski MA, Parsons AM, Funkhouser WK, Lee CB, Roberts PJ, Thorne L, Bernard PS, Perou CM, Hayes DN (2010) Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types. Clin Cancer Res 16(19):4864–4875. doi:10.1158/1078-0432.CCR-10-0199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winter SC, Buffa FM, Silva P, Miller C, Valentine HR, Turley H, Shah KA, Cox GJ, Corbridge RJ, Homer JJ, Musgrove B, Slevin N, Sloan P, Price P, West CM, Harris AL (2007) Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers. Cancer Res 67(7):3441–3449. doi:10.1158/0008-5472.CAN-06-3322

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Poh CF, Williams M, Laronde DM, Berean K, Gardner PJ, Jiang H, Wu L, Lee JJ, Rosin MP (2012) Loss of heterozygosity (LOH) profiles–validated risk predictors for progression to oral cancer. Cancer Prev Res (Phila) 5(9):1081–1089. doi:10.1158/1940-6207.CAPR-12-0173

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands

    Ruud H. Brakenhoff

  2. Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, Giessen, Germany

    Steffen Wagner & Jens P. Klussmann

Authors
  1. Ruud H. Brakenhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steffen Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jens P. Klussmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruud H. Brakenhoff .

Editor information

Editors and Affiliations

  1. Department of Head and Neck Surgery, Poznan University of Medical Sciences, The Greater Poland Cancer Centre, Poznań, Poland

    Wojciech Golusiński

  2. Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center/Cancer Center Amsterdam, Amsterdam, The Netherlands

    C. René Leemans

  3. Dept. of Head Medicine and Oral Health, University of Leipzig Clinic of Otolaryngology, Leipzig, Germany

    Andreas Dietz

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Brakenhoff, R.H., Wagner, S., Klussmann, J.P. (2017). Molecular Patterns and Biology of HPV-Associated HNSCC. In: Golusiński, W., Leemans, C., Dietz, A. (eds) HPV Infection in Head and Neck Cancer. Recent Results in Cancer Research, vol 206. Springer, Cham. https://doi.org/10.1007/978-3-319-43580-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-43580-0_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-43578-7

  • Online ISBN: 978-3-319-43580-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation