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Mutational Profile of HPV-Positive HNSCC

  • Hua Li
  • Jennifer R. GrandisEmail author
Chapter
  • 770 Downloads

Abstract

This chapter summarizes the mutational profile of head and neck squamous cell cancer (HNSCC) associated with infection of the human papillomavirus (HPV). Focusing on next-generation sequencing studies, the differences between the mutations detected in HPV-positive HNSCC and HPV-negative HNSCC were compared. The low frequency of TP53 mutations in HPV-positive HNSCC and the link between HPV and TP53 are reviewed. A comparison of gene mutations suggests that some genes are frequently mutated in HPV-positive HNSCC, including PIK3CA, FGER3, K-RAS, and MAPK1. While NOTCH1, TP63, and CASP8 are less frequently mutated in HPV-positive HNSCC. This chapter also reviews and compares the recurrent genomic alterations in HPV-positive HNSCC and cervical squamous cell carcinoma (CSCC), a cancer also linked to HPV infection. Finally, a brief review of the genetic alterations in nasopharyngeal carcinoma lined to infection with Epstein–Barr Virus infection is also reviewed.

Keywords

Head and neck squamous cell cancer Oropharyngeal squamous cell carcinoma Human papillomavirus Gene mutations Mutation frequency TP53 PIK3CA Therapeutic Cervical squamous cell carcinoma Nasopharyngeal carcinoma Epstein–Barr virus 

Abbreviations

AKT

Protein kinase B

APOBEC

Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like

ASXL3

Additional sex combs like 3

B2M

Beta-2-microglobulin

CASP8

Caspase 8, apoptosis-related cysteine peptidase

CBFB

Core-binding factor, beta subunit

CDKN2A

Cyclin-dependent kinase inhibitor 2A

CSCC

Cervical squamous cell carcinoma

CUL3

Cullin 3

DDR2

Discoidin domain receptor tyrosine kinase 2

DDX3X

DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked

EBV

Epstein–Barr Virus

EGFR

Epidermal growth factor receptor

ELF3

E74-like factor 3

EP300

E1A binding protein p300

ERBB2

v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2

EZH2

Enhancer of zeste homolog 2

FBXW7

F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase

FGFR1/3

Fibroblast growth factor receptor 1/3

H-RAS

Harvey rat sarcoma viral oncogene homolog

HNSCC

Head and neck squamous cell carcinoma

HPV

Human Papillomavirus

HUWE1

HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase

K-RAS

Kirsten rat sarcoma viral oncogene homolog

KCNT2

Potassium channel, subfamily T, member 2

Lingo2

Leucine rich repeat and Ig domain containing 2

LMP1

Epstein–Barr virus latent membrane protein 1

MAPK1

Mitogen-activated protein kinase 1

MLL2/3

Lysine (K)-specific methyltransferase 2D/C

mTOR

Mechanistic target of rapamycin

NF1

Neurofibromin 1

NOTCH1

Notch 1

NPC

Nasopharyngeal carcinoma

NSD1

Nuclear receptor binding SET domain protein 1

OPSCC

Oropharyngeal squamous cell carcinomas

PI3 K

Phosphainositide-3-kinase

PIK3CA

Phosphoinositide-3-kinase, catalytic, alpha polypeptide

PRAD-1

Cyclin D1

PTEN

Phosphatase and tensin homolog

RB

Retinoblastoma

RPPA

Reverse-phase protein array

shRNA

Short hairpin RNA

STK11

Serine/threonine kinase 11

TCGA

The Cancer Genome Atlas

TP53

Tumor protein p53

TP63

Tumor protein p63

WES

Whole-exome sequencing

ZNF750

Zinc finger protein 750

References

  1. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Trevino L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333(6046):1154–1157. doi: 10.1126/science.1206923 PubMedCentralPubMedCrossRefGoogle Scholar
  2. Andl T, Kahn T, Pfuhl A, Nicola T, Erber R, Conradt C, Klein W, Helbig M, Dietz A, Weidauer H, Bosch FX (1998) Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res 58(1):5–13PubMedGoogle Scholar
  3. Ando M, Kawazu M, Ueno T, Fukumura K, Yamato A, Soda M, Yamashita Y, Choi YL, Yamasoba T, Mano H (2013) Cancer-associated missense mutations of caspase-8 activate nuclear factor-kappaB signaling. Cancer Sci 104(8):1002–1008. doi: 10.1111/cas.12191 PubMedCrossRefGoogle Scholar
  4. Arora S, Aggarwal P, Pathak A, Bhandari R, Duffoo F, Gulati SC (2012) Molecular genetics of head and neck cancer (Review). Mol Med Rep 6(1):19–22. doi: 10.3892/mmr.2012.889 PubMedGoogle Scholar
  5. Arvind R, Shimamoto H, Momose F, Amagasa T, Omura K, Tsuchida N (2005) A mutation in the common docking domain of ERK2 in a human cancer cell line, which was associated with its constitutive phosphorylation. Int J Oncol 27(6):1499–1504PubMedGoogle Scholar
  6. Begum S, Cao D, Gillison M, Zahurak M, Westra WH (2005) Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma. Clin Cancer Res: An Official J Am Assoc Cancer Res 11(16):5694–5699. doi: 10.1158/1078-0432.CCR-05-0587 CrossRefGoogle Scholar
  7. Bei JX, Li Y, Jia WH, Feng BJ, Zhou G, Chen LZ, Feng QS, Low HQ, Zhang H, He F, Tai ES, Kang T, Liu ET, Liu J, Zeng YX (2010) A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nat Genet 42(7):599–603. doi: 10.1038/ng.601 PubMedCrossRefGoogle Scholar
  8. Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH (2003) A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res 63(8):1727–1730PubMedGoogle Scholar
  9. Bradford CR, Zhu S, Ogawa H, Ogawa T, Ubell M, Narayan A, Johnson G, Wolf GT, Fisher SG, Carey TE (2003) P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines. Head Neck 25(8):654–661. doi: 10.1002/hed.10274 PubMedCrossRefGoogle Scholar
  10. Brennan JA, Boyle JO, Koch WM, Goodman SN, Hruban RH, Eby YJ, Couch MJ, Forastiere AA, Sidransky D (1995) Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med 332(11):712–717. doi: 10.1056/NEJM199503163321104 PubMedCrossRefGoogle Scholar
  11. Brimer N, Lyons C, Wallberg AE, Vande Pol SB (2012) Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling. Oncogene 31(43):4639–4646. doi: 10.1038/onc.2011.589 PubMedCentralPubMedCrossRefGoogle Scholar
  12. Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, Refsland EW, Kotandeniya D, Tretyakova N, Nikas JB, Yee D, Temiz NA, Donohue DE, McDougle RM, Brown WL, Law EK, Harris RS (2013a) APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494(7437):366–370. doi: 10.1038/nature11881 PubMedCentralPubMedCrossRefGoogle Scholar
  13. Burns MB, Temiz NA, Harris RS (2013b) Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet 45(9):977–983. doi: 10.1038/ng.2701 PubMedCentralPubMedCrossRefGoogle Scholar
  14. Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP, Radvanyi F (1999) Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 23(1):18–20. doi: 10.1038/12615 PubMedCrossRefGoogle Scholar
  15. Chiosea SI, Grandis JR, Lui VW, Diergaarde B, Maxwell JH, Ferris RL, Kim SW, Luvison A, Miller M, Nikiforova MN (2013) PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma. BMC Cancer 13:602. doi: 10.1186/1471-2407-13-602 PubMedCentralPubMedCrossRefGoogle Scholar
  16. Chou A, Dekker N, Jordan RC (2009) Identification of novel fibroblast growth factor receptor 3 gene mutations in actinic cheilitis and squamous cell carcinoma of the lip. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107(4):535–541. doi: 10.1016/j.tripleo.2008.12.050 PubMedCentralPubMedCrossRefGoogle Scholar
  17. Conticello SG (2008) The AID/APOBEC family of nucleic acid mutators. Genome Biol 9(6):229. doi: 10.1186/gb-2008-9-6-229 PubMedCentralPubMedCrossRefGoogle Scholar
  18. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356(19):1944–1956. doi: 10.1056/NEJMoa065497 PubMedCrossRefGoogle Scholar
  19. Dickens LS, Boyd RS, Jukes-Jones R, Hughes MA, Robinson GL, Fairall L, Schwabe JW, Cain K, Macfarlane M (2012) A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol Cell 47(2):291–305. doi: 10.1016/j.molcel.2012.05.004 PubMedCentralPubMedCrossRefGoogle Scholar
  20. Dutton A, Woodman CB, Chukwuma MB, Last JI, Wei W, Vockerodt M, Baumforth KR, Flavell JR, Rowe M, Taylor AM, Young LS, Murray PG (2007) Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells. Blood 109(6):2597–2603. doi: 10.1182/blood-2006-05-020545 PubMedCrossRefGoogle Scholar
  21. Egloff AM, Grandis JR (2009) Improving response Rates to EGFR-targeted therapies for head and neck squamous cell carcinoma: candidate predictive biomarkers and combination treatment with src inhibitors. J Oncol 2009:896407. doi: 10.1155/2009/896407 PubMedCentralPubMedCrossRefGoogle Scholar
  22. Engelman JA (2009) Targeting PI3 K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9(8):550–562. doi: 10.1038/nrc2664 PubMedCrossRefGoogle Scholar
  23. Eswarakumar VP, Lax I, Schlessinger J (2005) Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 16(2):139–149. doi: 10.1016/j.cytogfr.2005.01.001 PubMedCrossRefGoogle Scholar
  24. Forbes SA, Bhamra G, Bamford S, Dawson E, Kok C, Clements J, Menzies A, Teague JW, Futreal PA, Stratton MR (2008) The catalogue of somatic mutations in cancer (COSMIC). In: Haines JL (et al) Current protocols in human genetics/editorial board. doi: 10.1002/0471142905.hg1011s57
  25. Franceschi S, Gloghini A, Maestro R, Barzan L, Bidoli E, Talamini R, Vukosavljevic T, Carbone A, Boiocchi M (1995) Analysis of the p53 gene in relation to tobacco and alcohol in cancers of the upper aero-digestive tract. Int J Cancer 60(6):872–876PubMedCrossRefGoogle Scholar
  26. Gasco M, Crook T (2003) The p53 network in head and neck cancer. Oral Oncol 39(3):222–231PubMedCrossRefGoogle Scholar
  27. Gaykalova DA, Mambo E, Choudhary A, Houghton J, Buddavarapu K, Sanford T, Darden W, Adai A, Hadd A, Latham G, Danilova LV, Bishop J, Li RJ, Westra WH, Hennessey P, Koch WM, Ochs MF, Califano JA, Sun W (2014) Novel insight into mutational landscape of head and neck squamous cell carcinoma. PLoS One 9(3):e93102. doi: 10.1371/journal.pone.0093102 PubMedCentralPubMedCrossRefGoogle Scholar
  28. Gentile M, Ahnstrom M, Schon F, Wingren S (2001) Candidate tumour suppressor genes at 11q23-q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis. Oncogene 20(53):7753–7760. doi: 10.1038/sj.onc.1204993 PubMedCrossRefGoogle Scholar
  29. Henderson S, Chakravarthy A, Su X, Boshoff C, Fenton TR (2014) APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development. Cell Rep 7(6):1833–1841. doi: 10.1016/j.celrep.2014.05.012 PubMedCrossRefGoogle Scholar
  30. Hui AB, Or YY, Takano H, Tsang RK, To KF, Guan XY, Sham JS, Hung KW, Lam CN, van Hasselt CA, Kuo WL, Gray JW, Huang DP, Lo KW (2005) Array-based comparative genomic hybridization analysis identified cyclin D1 as a target oncogene at 11q13.3 in nasopharyngeal carcinoma. Cancer Res 65(18):8125–8133. doi: 10.1158/0008-5472.CAN-05-0648 PubMedCrossRefGoogle Scholar
  31. Jang SJ, Chiba I, Hirai A, Hong WK, Mao L (2001) Multiple oral squamous epithelial lesions: are they genetically related? Oncogene 20(18):2235–2242. doi: 10.1038/sj.onc.1204311 PubMedCrossRefGoogle Scholar
  32. Janku F, Wheler JJ, Naing A, Falchook GS, Hong DS, Stepanek VM, Fu S, Piha-Paul SA, Lee JJ, Luthra R, Tsimberidou AM, Kurzrock R (2013) PIK3CA mutation H1047R is associated with response to PI3 K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res 73(1):276–284. doi: 10.1158/0008-5472.CAN-12-1726 PubMedCentralPubMedCrossRefGoogle Scholar
  33. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi: 10.3322/caac.20107 PubMedCrossRefGoogle Scholar
  34. Jia WH, Huang QH, Liao J, Ye W, Shugart YY, Liu Q, Chen LZ, Li YH, Lin X, Wen FL, Adami HO, Zeng Y, Zeng YX (2006) Trends in incidence and mortality of nasopharyngeal carcinoma over a 20–25 year period (1978/1983–2002) in Sihui and Cangwu counties in southern China. BMC Cancer 6:178. doi: 10.1186/1471-2407-6-178 PubMedCentralPubMedCrossRefGoogle Scholar
  35. Jin C, Jin Y, Wennerberg J, Akervall J, Dictor M, Mertens F (2002) Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the head and neck. Cancer Genet Cytogenet 132(2):85–96PubMedCrossRefGoogle Scholar
  36. Kawaguchi H, Ohno S, Araki K, Miyazaki M, Saeki H, Watanabe M, Tanaka S, Sugimachi K (2000) p53 polymorphism in human papillomavirus-associated esophageal cancer. Cancer Res 60(11):2753–2755PubMedGoogle Scholar
  37. Kim JC, Koo KH, Roh SA, Cho YK, Kim HC, Yu CS, Kim HJ, Kim JS, Cho MK (2003) Genetic and epigenetic changes in the APC gene in sporadic colorectal carcinoma with synchronous adenoma. Int J Colorectal Dis 18(3):203–209. doi: 10.1007/s00384-002-0449-9 PubMedGoogle Scholar
  38. Knowles LM, Stabile LP, Egloff AM, Rothstein ME, Thomas SM, Gubish CT, Lerner EC, Seethala RR, Suzuki S, Quesnelle KM, Morgan S, Ferris RL, Grandis JR, Siegfried JM (2009) HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer. Clinical Cancer Res: An Official J Am Assoc Cancer Res 15(11):3740–3750. doi: 10.1158/1078-0432.CCR-08-3252 CrossRefGoogle Scholar
  39. Kumar B, Cordell KG, Lee JS, Worden FP, Prince ME, Tran HH, Wolf GT, Urba SG, Chepeha DB, Teknos TN, Eisbruch A, Tsien CI, Taylor JM, D’Silva NJ, Yang K, Kurnit DM, Bauer JA, Bradford CR, Carey TE (2008) EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol: Official Journal Am Soc Clin Oncol 26(19):3128–3137. doi: 10.1200/JCO.2007.12.7662 CrossRefGoogle Scholar
  40. Lai S, Batsakis J, Ordonez N, Luna M, Goepfert H, Elnaggar A (1995) Genotypic and phenotypic alterations of p53 in head and neck squamous-cell carcinoma. Oncol Rep 2(6):1115–1120PubMedGoogle Scholar
  41. 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 PubMedCentralPubMedCrossRefGoogle Scholar
  42. Lechner M, Frampton GM, Fenton T, Feber A, Palmer G, Jay A, Pillay N, Forster M, Cronin MT, Lipson D, Miller VA, Brennan TA, Henderson S, Vaz F, O’Flynn P, Kalavrezos N, Yelensky R, Beck S, Stephens PJ, Boshoff C (2013) Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors. Genome medicine 5(5):49. doi: 10.1186/gm453 PubMedCentralPubMedCrossRefGoogle Scholar
  43. 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 PubMedCrossRefGoogle Scholar
  44. Leonard B, Hart SN, Burns MB, Carpenter MA, Temiz NA, Rathore A, Vogel RI, Nikas JB, Law EK, Brown WL, Li Y, Zhang Y, Maurer MJ, Oberg AL, Cunningham JM, Shridhar V, Bell DA, April C, Bentley D, Bibikova M, Cheetham RK, Fan JB, Grocock R, Humphray S, Kingsbury Z, Peden J, Chien J, Swisher EM, Hartmann LC, Kalli KR, Goode EL, Sicotte H, Kaufmann SH, Harris RS (2013) APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma. Cancer Res 73(24):7222–7231. doi: 10.1158/0008-5472.CAN-13-1753 PubMedCrossRefGoogle Scholar
  45. Li C, Egloff AM, Sen M, Grandis JR, Johnson DE (2014) Caspase-8 mutations in head and neck cancer confer resistance to death receptor-mediated apoptosis and enhance migration, invasion, and tumor growth. Mol Oncol. doi: 10.1016/j.molonc.2014.03.018 PubMedCentralGoogle Scholar
  46. Li HM, Man C, Jin Y, Deng W, Yip YL, Feng HC, Cheung YC, Lo KW, Meltzer PS, Wu ZG, Kwong YL, Yuen AP, Tsao SW (2006) Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase. Int J Cancer 119(7):1567–1576. doi: 10.1002/ijc.22032 PubMedCrossRefGoogle Scholar
  47. Li L, Tao Q, Jin H, van Hasselt A, Poon FF, Wang X, Zeng MS, Jia WH, Zeng YX, Chan AT, Cao Y (2010) The tumor suppressor UCHL1 forms a complex with p53/MDM2/ARF to promote p53 signaling and is frequently silenced in nasopharyngeal carcinoma. Clin Cancer Res: Official J Am Assoc Cancer Res 16(11):2949–2958. doi: 10.1158/1078-0432.CCR-09-3178 CrossRefGoogle Scholar
  48. Liao RG, Jung J, Tchaicha J, Wilkerson MD, Sivachenko A, Beauchamp EM, Liu Q, Pugh TJ, Pedamallu CS, Hayes DN, Gray NS, Getz G, Wong KK, Haddad RI, Meyerson M, Hammerman PS (2013) Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma. Cancer Res 73(16):5195–5205. doi: 10.1158/0008-5472.CAN-12-3950 PubMedCentralPubMedCrossRefGoogle Scholar
  49. Liu P, Fang X, Feng Z, Guo YM, Peng RJ, Liu T, Huang Z, Feng Y, Sun X, Xiong Z, Guo X, Pang SS, Wang B, Lv X, Feng FT, Li DJ, Chen LZ, Feng QS, Huang WL, Zeng MS, Bei JX, Zhang Y, Zeng YX (2011) Direct sequencing and characterization of a clinical isolate of Epstein-Barr virus from nasopharyngeal carcinoma tissue by using next-generation sequencing technology. J Virol 85(21):11291–11299. doi: 10.1128/JVI.00823-11 PubMedCentralPubMedCrossRefGoogle Scholar
  50. Lo KW, Cheung ST, Leung SF, van Hasselt A, Tsang YS, Mak KF, Chung YF, Woo JK, Lee JC, Huang DP (1996) Hypermethylation of the p16 gene in nasopharyngeal carcinoma. Cancer Res 56(12):2721–2725PubMedGoogle Scholar
  51. Lo KW, Chung GT, To KF (2012) Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol 22(2):79–86. doi: 10.1016/j.semcancer.2011.12.011 PubMedCrossRefGoogle Scholar
  52. Lo KW, Huang DP, Lau KM (1995) p16 gene alterations in nasopharyngeal carcinoma. Cancer Res 55(10):2039–2043PubMedGoogle Scholar
  53. Logie A, Dunois-Larde C, Rosty C, Levrel O, Blanche M, Ribeiro A, Gasc JM, Jorcano J, Werner S, Sastre-Garau X, Thiery JP, Radvanyi F (2005) Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans. Hum Mol Genet 14(9):1153–1160. doi: 10.1093/hmg/ddi127 PubMedCrossRefGoogle Scholar
  54. Lui VW, Hedberg ML, Li H, Vangara BS, Pendleton K, Zeng Y, Lu Y, Zhang Q, Du Y, Gilbert BR, Freilino M, Sauerwein S, Peyser ND, Xiao D, Diergaarde B, Wang L, Chiosea S, Seethala R, Johnson JT, Kim S, Duvvuri U, Ferris RL, Romkes M, Nukui T, Kwok-Shing Ng P, Garraway LA, Hammerman PS, Mills GB, Grandis JR (2013) Frequent mutation of the PI3 K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov 3(7):761–769. doi: 10.1158/2159-8290.CD-13-0103 PubMedCentralPubMedCrossRefGoogle Scholar
  55. Lyronis ID, Baritaki S, Bizakis I, Krambovitis E, Spandidos DA (2008) K-ras mutation, HPV infection and smoking or alcohol abuse positively correlate with esophageal squamous carcinoma. Pathol Oncol Res POR 14(3):267–273. doi: 10.1007/s12253-008-9032-1 PubMedCrossRefGoogle Scholar
  56. Mandruzzato S, Brasseur F, Andry G, Boon T, van der Bruggen P (1997) A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma. J Exp Med 186(5):785–793PubMedCentralPubMedCrossRefGoogle Scholar
  57. Martin DA, Siegel RM, Zheng L, Lenardo MJ (1998) Membrane oligomerization and cleavage activates the caspase-8 (FLICE/MACHalpha1) death signal. J Biol Chem 273(8):4345–4349PubMedCrossRefGoogle Scholar
  58. Maruyama H, Yasui T, Ishikawa-Fujiwara T, Morii E, Yamamoto Y, Yoshii T, Takenaka Y, Nakahara S, Todo T, Hongyo T, Inohara H (2014) Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population. Cancer Sci 105(4):409–417. doi: 10.1111/cas.12369 PubMedCrossRefGoogle Scholar
  59. McDermott AL, Dutt SN, Watkinson JC (2001) The aetiology of nasopharyngeal carcinoma. Clin Otolaryngol Allied Sci 26(2):82–92PubMedCrossRefGoogle Scholar
  60. Meyers JM, Spangle JM, Munger K (2013) The human papillomavirus type 8 E6 protein interferes with NOTCH activation during keratinocyte differentiation. J Virol 87(8):4762–4767. doi: 10.1128/JVI.02527-12 PubMedCentralPubMedCrossRefGoogle Scholar
  61. Morrison JA, Gulley ML, Pathmanathan R, Raab-Traub N (2004) Differential signaling pathways are activated in the Epstein-Barr virus-associated malignancies nasopharyngeal carcinoma and Hodgkin lymphoma. Cancer Res 64(15):5251–5260. doi: 10.1158/0008-5472.CAN-04-0538 PubMedCrossRefGoogle Scholar
  62. Murugan AK, Hong NT, Fukui Y, Munirajan AK, Tsuchida N (2008) Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas. Int J Oncol 32(1):101–111PubMedGoogle Scholar
  63. Nichols AC, Palma DA, Chow W, Tan S, Rajakumar C, Rizzo G, Fung K, Kwan K, Wehrli B, Winquist E, Koropatnick J, Mymryk JS, Yoo J, Barrett JW (2013) High frequency of activating PIK3CA mutations in human papillomavirus-positive oropharyngeal cancer. JAMA Otolaryngol-Head Neck Surg 139(6):617–622. doi: 10.1001/jamaoto.2013.3210 PubMedCrossRefGoogle Scholar
  64. Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, Cherniack AD, Ambrogio L, Cibulskis K, Bertelsen B, Romero-Cordoba S, Trevino V, Vazquez-Santillan K, Guadarrama AS, Wright AA, Rosenberg MW, Duke F, Kaplan B, Wang R, Nickerson E, Walline HM, Lawrence MS, Stewart C, Carter SL, McKenna A, Rodriguez-Sanchez IP, Espinosa-Castilla M, Woie K, Bjorge L, Wik E, Halle MK, Hoivik EA, Krakstad C, Gabino NB, Gomez-Macias GS, Valdez-Chapa LD, Garza-Rodriguez ML, Maytorena G, Vazquez J, Rodea C, Cravioto A, Cortes ML, Greulich H, Crum CP, Neuberg DS, Hidalgo-Miranda A, Escareno CR, Akslen LA, Carey TE, Vintermyr OK, Gabriel SB, Barrera-Saldana HA, Melendez-Zajgla J, Getz G, Salvesen HB, Meyerson M (2014) Landscape of genomic alterations in cervical carcinomas. Nature 506(7488):371–375. doi: 10.1038/nature12881 PubMedCentralPubMedCrossRefGoogle Scholar
  65. Olshan AF, Weissler MC, Pei H, Conway K, Anderson S, Fried DB, Yarbrough WG (1997) Alterations of the p16 gene in head and neck cancer: frequency and association with p53, PRAD-1 and HPV. Oncogene 14(7):811–818. doi: 10.1038/sj.onc.1200892 PubMedCrossRefGoogle Scholar
  66. Or YY, Chung GT, To KF, Chow C, Choy KW, Tong CY, Leung AW, Hui AB, Tsao SW, Ng HK, Yip TT, Busson P, Lo KW (2010) Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma. J Pathol 220(1):97–107. doi: 10.1002/path.2609 PubMedCrossRefGoogle Scholar
  67. Or YY, Hui AB, To KF, Lam CN, Lo KW (2006) PIK3CA mutations in nasopharyngeal carcinoma. Int J Cancer 118(4):1065–1067. doi: 10.1002/ijc.21444 PubMedCrossRefGoogle Scholar
  68. Perrone F, Suardi S, Pastore E, Casieri P, Orsenigo M, Caramuta S, Dagrada G, Losa M, Licitra L, Bossi P, Staurengo S, Oggionni M, Locati L, Cantu G, Squadrelli M, Carbone A, Pierotti MA, Pilotti S (2006) Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma. Clin Cancer Res: Official J Am Assoc Cancer Res 12(22):6643–6651. doi: 10.1158/1078-0432.CCR-06-1759 CrossRefGoogle Scholar
  69. Peyssonnaux C, Eychene A (2001) The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell/Under Auspices Eur Cell Biol Organ 93(1–2):53–62CrossRefGoogle Scholar
  70. Pickering CR, Zhang J, Yoo SY, Bengtsson L, Moorthy S, Neskey DM, Zhao M, Ortega Alves MV, Chang K, Drummond J, Cortez E, Xie TX, Zhang D, Chung W, Issa JP, Zweidler-McKay PA, Wu X, El-Naggar AK, Weinstein JN, Wang J, Muzny DM, Gibbs RA, Wheeler DA, Myers JN, Frederick MJ (2013) Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 3(7):770–781. doi: 10.1158/2159-8290.CD-12-0537 PubMedCrossRefGoogle Scholar
  71. Raff AB, Woodham AW, Raff LM, Skeate JG, Yan L, Da Silva DM, Schelhaas M, Kast WM (2013) The evolving field of human papillomavirus receptor research: a review of binding and entry. J Virol 87(11):6062–6072. doi: 10.1128/JVI.00330-13 PubMedCentralPubMedCrossRefGoogle Scholar
  72. Rampias T, Sasaki C, Psyrri A (2014) Molecular mechanisms of HPV induced carcinogenesis in head and neck. Oral Oncol 50(5):356–363. doi: 10.1016/j.oraloncology.2013.07.011 PubMedCrossRefGoogle Scholar
  73. Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, Kiezun A, Kryukov GV, Carter SL, Saksena G, Harris S, Shah RR, Resnick MA, Getz G, Gordenin DA (2013) An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 45(9):970–976. doi: 10.1038/ng.2702 PubMedCentralPubMedCrossRefGoogle Scholar
  74. Safdari Y, Khalili M, Farajnia S, Asgharzadeh M, Yazdani Y, Sadeghi M (2014) Recent advances in head and neck squamous cell carcinoma—a review. Clin Biochem. doi: 10.1016/j.clinbiochem.2014.05.066 PubMedGoogle Scholar
  75. Schleich K, Krammer PH, Lavrik IN (2013) The chains of death: a new view on caspase-8 activation at the DISC. Cell Cycle 12(2):193–194. doi: 10.4161/cc.23464 PubMedCentralPubMedCrossRefGoogle Scholar
  76. 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: Official J Am Assoc Cancer Res 20(9):2300–2311. doi: 10.1158/1078-0432.CCR-13-2585 CrossRefGoogle Scholar
  77. Sheu JJ, Hua CH, Wan L, Lin YJ, Lai MT, Tseng HC, Jinawath N, Tsai MH, Chang NW, Lin CF, Lin CC, Hsieh LJ, Wang TL, Shih Ie M, Tsai FJ (2009) Functional genomic analysis identified epidermal growth factor receptor activation as the most common genetic event in oral squamous cell carcinoma. Cancer Res 69(6):2568–2576. doi: 10.1158/0008-5472.CAN-08-3199 PubMedCrossRefGoogle Scholar
  78. Shi W, Bastianutto C, Li A, Perez-Ordonez B, Ng R, Chow KY, Zhang W, Jurisica I, Lo KW, Bayley A, Kim J, O’Sullivan B, Siu L, Chen E, Liu FF (2006) Multiple dysregulated pathways in nasopharyngeal carcinoma revealed by gene expression profiling. Int J Cancer 119(10):2467–2475. doi: 10.1002/ijc.22107 PubMedCrossRefGoogle Scholar
  79. Shotelersuk V, Ittiwut C, Shotelersuk K, Triratanachat S, Poovorawan Y, Mutirangura A (2001) Fibroblast growth factor receptor 3 S249C mutation in virus associated squamous cell carcinomas. Oncol Rep 8(6):1301–1304PubMedGoogle Scholar
  80. Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, Brown C, Pugh TJ, Stojanov P, Cho J, Lawrence MS, Getz G, Brägelmann J, DeBoer R, Weichselbaum RR, Langerman A, Portugal L, Blair E, Stenson K, Lingen MW, Cohen EEW, Vokes EE, White KP, Hammerman PS (2014) Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res (In press)Google Scholar
  81. Sisk EA, Soltys SG, Zhu S, Fisher SG, Carey TE, Bradford CR (2002) Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma. Head Neck 24(9):841–849. doi: 10.1002/hed.10146 PubMedCrossRefGoogle Scholar
  82. 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 PubMedCrossRefGoogle Scholar
  83. Soung YH, Lee JW, Kim SY, Jang J, Park YG, Park WS, Nam SW, Lee JY, Yoo NJ, Lee SH (2005a) CASPASE-8 gene is inactivated by somatic mutations in gastric carcinomas. Cancer Res 65(3):815–821PubMedGoogle Scholar
  84. Soung YH, Lee JW, Kim SY, Sung YJ, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH (2005b) Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas. Oncogene 24(1):141–147. doi: 10.1038/sj.onc.1208244 PubMedCrossRefGoogle Scholar
  85. Spruck CH 3rd, Tsai YC, Huang DP, Yang AS, Rideout WM 3rd, Gonzalez-Zulueta M, Choi P, Lo KW, Yu MC, Jones PA (1992) Absence of p53 gene mutations in primary nasopharyngeal carcinomas. Cancer Res 52(17):4787–4790PubMedGoogle Scholar
  86. Stadler ME, Patel MR, Couch ME, Hayes DN (2008) Molecular biology of head and neck cancer: risks and pathways. Hematol/Oncol Clin North Am 22(6):1099–1124. doi: 10.1016/j.hoc.2008.08.007
  87. Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, Breuer J, Leigh IM, Matlashewski G, Banks L (1998) Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 393(6682):229–234. doi: 10.1038/30400 PubMedCrossRefGoogle Scholar
  88. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333(6046):1157–1160. doi: 10.1126/science.1208130 PubMedCentralPubMedCrossRefGoogle Scholar
  89. Surviladze Z, Sterk RT, DeHaro SA, Ozbun MA (2013) Cellular entry of human papillomavirus type 16 involves activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway and inhibition of autophagy. J Virol 87(5):2508–2517. doi: 10.1128/JVI.02319-12 PubMedCentralPubMedCrossRefGoogle Scholar
  90. Tan MJ, White EA, Sowa ME, Harper JW, Aster JC, Howley PM (2012) Cutaneous beta-human papillomavirus E6 proteins bind mastermind-like coactivators and repress notch signaling. Proc Natl Acad Sci USA 109(23):E1473–E1480. doi: 10.1073/pnas.1205991109 PubMedCentralPubMedCrossRefGoogle Scholar
  91. Thunnissen FB, Prinsen C, Hol B, Van der Drift M, Vesin A, Brambilla C, Montuenga L, Field JK, consortium E (2012) Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development. Lung Cancer 75(2):156–160. doi: 10.1016/j.lungcan.2011.07.013 PubMedCrossRefGoogle Scholar
  92. Tsai CL, Li HP, Lu YJ, Hsueh C, Liang Y, Chen CL, Tsao SW, Tse KP, Yu JS, Chang YS (2006) Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling. Cancer Res 66(24):11668–11676. doi: 10.1158/0008-5472.CAN-06-2194 PubMedCrossRefGoogle Scholar
  93. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1):12–19. doi: 10.1002/(SICI)1096-9896(199909)189:1<12:AID-PATH431>3.0.CO;2-F PubMedCrossRefGoogle Scholar
  94. Wei WI, Sham JS (2005) Nasopharyngeal carcinoma. Lancet 365(9476):2041–2054. doi: 10.1016/S0140-6736(05)66698-6 PubMedCrossRefGoogle Scholar
  95. Wiest T, Schwarz E, Enders C, Flechtenmacher C, Bosch FX (2002) Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene 21(10):1510–1517. doi: 10.1038/sj.onc.1205214 PubMedCrossRefGoogle Scholar
  96. Williams MD (2010) Integration of biomarkers including molecular targeted therapies in head and neck cancer. Head Neck Pathol 4(1):62–69. doi: 10.1007/s12105-010-0166-6 PubMedCentralPubMedCrossRefGoogle Scholar
  97. Yoshizaki T (2011) A novel immune evasion mechanism of LMP-1, an EBV-primary oncogene, in nasopharyngeal carcinoma. Adv Otorhinolaryngol 72:157–159. doi: 10.1159/000324780 PubMedGoogle Scholar
  98. Zhang Y, Hiraishi Y, Wang H, Sumi KS, Hayashido Y, Toratani S, Kan M, Sato JD, Okamoto T (2005) Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas. Int J Cancer 117(1):166–168. doi: 10.1002/ijc.21145 PubMedCrossRefGoogle Scholar
  99. Zhang ZC, Fu S, Wang F, Wang HY, Zeng YX, Shao JY (2014) Oncogene mutational profile in nasopharyngeal carcinoma. OncoTargets Ther 7:457–467. doi: 10.2147/OTT.S58791 Google Scholar
  100. Zsakai L, Nemeth G, Szantai-Kis C, Greff Z, Horvath Z, Szokol B, Baska F, Boon TC, Orfi L, Keri G (2013) Developing FGFR inhibitors as potential anti-cancer agents. Acta Pharm Hung 83(2):47–56PubMedGoogle Scholar
  101. zur Hausen H (2009) Human papillomavirus and cervical cancer. Indian J Med Res 130(3):209PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Otolaryngology Head and Neck SurgeryUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Departments of Otolaryngology Head and Neck SurgeryClinical and Translational Science Institute, University of California, San FranciscoSan FranciscoUSA

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