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Molecular Diagnostics in Head and Neck Squamous Cell Carcinoma

  • Nuzhat Husain
  • Azfar Neyaz
Chapter

Abstract

Molecular diagnostics in Head and Neck Squamous cell carcinoma (HNSCC) is implemented in clinical practice to define the HPV-associated lesions specifically in the Oropharyngeal Squamous cell carcinoma (OPSCC), which has been separated from the conventional tobacco-related Non-HPV subtype and is known to have a better prognosis, different morphology as well as expression of p16 as a surrogate marker for HPV infection. HPV related lesions occur at other sites in the head and neck and relatively infrequent and not characterized as a distinguished entity. Tobacco-related cancers show p53 and cyclin D1 mutations and also show field carcinogenesis in a multistep progression of malignancy which may be useful in staging the lesion as well as in detecting molecular margins or molecular metastasis. Specific variants of HNSCC require mutation testing, for example, NUT carcinoma to get to a diagnosis. The chapter also addresses issues of HPV testing, epigenetic changes and chromosomal alterations in HNSCC as well the role of liquid biopsy in patients with HNSCC.

Keywords

Head and Neck squamous cell carcinoma HPV Molecular diagnosis 

Notes

Acknowledgments

Sources of support, including pharmaceutical and industry support that require acknowledgment: None.

Disclosure of funding: None.

Conflict of interest: None.

References

  1. 1.
    Parkin DM, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRefGoogle Scholar
  2. 2.
    D’Costa J, et al. Detection of HPV-16 genome in human oral cancers and potentially malignant lesions from India. Oral Oncol. 1998;34(5):413–20.PubMedCrossRefGoogle Scholar
  3. 3.
    Sankaranarayanan R, et al. Trivandrum Oral Cancer Screening Study Group. Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet. 2005;365(9475):1927–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Byakodi R, et al. Oral cancer in India: an epidemiologic and clinical review. J Community Health. 2012;37(2):316–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Amin MB, et al. AJCC cancer staging manual. 8th ed. New York: Springer; 2017.CrossRefGoogle Scholar
  6. 6.
    Koch WM. Early diagnosis and treatment of cancer series: head and neck cancers. 1st ed. New York: Elsevier; 2010. Chapter 1—Molecular gene alterations as early-detection markers; page 1–18.Google Scholar
  7. 7.
    Gupta S, et al. Understanding molecular markers in recurrent oral squamous cell carcinoma treated with chemoradiation. Heliyon. 2016;2(12):e00206. eCollection 2016 Dec.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Levine AJ, et al. The p53 tumour suppressor gene. Nature. 1991;351(6326):453–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Sigal A, Rotter V. Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. Cancer Res. 2000;60(24):6788–93.PubMedGoogle Scholar
  10. 10.
    Soussi T, Wiman KG. Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell. 2007;12(4):303–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Shin DM, et al. p53 expressions: predicting recurrence and second primary tumors in head and neck squamous cell carcinoma. J Natl Cancer Inst. 1996;88(8):519–29.PubMedCrossRefGoogle Scholar
  12. 12.
    Singh V, et al. p16 and p53 in HPV-positive versus HPV-negative oral squamous cell carcinoma: do pathways differ? J Oral Pathol Med. 2017;46(9):744–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Fakhry C, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Forte T, et al. Incidence trends in head and neck cancers and human papillomavirus (HPV)-associated oropharyngeal cancer in Canada, 1992-2009. Cancer Causes Control. 2012;23:1343–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Gillison ML, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307(7):693–703.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Hwang TZ, et al. Incidence trends of human papillomavirus-related head and neck cancer in Taiwan, 1995-2009. Int J Cancer. 2015;137:395–408.PubMedCrossRefGoogle Scholar
  17. 17.
    Gillison ML, Alemany L, Snijders PJ, Chaturvedi A, Steinberg BM, Schwartz S, et al. Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis. Vaccine. 2012;30(Suppl 5):F34–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Gillison ML, D’Souza G, Westra W, Sugar E, Xiao W, Begum S, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100(6):407–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Heck JE, et al. Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Int J Epidemiol. 2010;39(1):166–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Marks MA, et al. Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium. Cancer Epidemiol Biomarkers Prev. 2014;23(1):160–71.PubMedCrossRefGoogle Scholar
  21. 21.
    El-Mofty SK, Patil S. Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):339–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Wenig BM. Squamous cell carcinoma of the upper aerodigestive tract: dysplasia and select variants. Mod Pathol. 2017;30(s1):S112–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Westra WH. The morphologic profile of HPV-related head and neck squamous carcinoma: implications for diagnosis, prognosis, and clinical management. Head Neck Pathol. 2012;6(Suppl 1):S48–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Yasui T, et al. Human papillomavirus and cystic node metastasis in oropharyngeal cancer and cancer of unknown primary origin. PLoS One. 2014;9(4):e95364.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Ang KK, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Kraft S, et al. HPV-associated neuroendocrine carcinoma of the oropharynx: a rare new entity with potentially aggressive clinical behavior. Am J Surg Pathol. 2012;36(3):321–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Gondim DD, Haynes W, Wang X, Chernock RD, El-Mofty SK, Lewis JS Jr. Histologic typing in oropharyngeal squamous cell carcinoma: a 4-year prospective practice study with p16 and high-risk HPV mRNA testing correlation. Am J Surg Pathol. 2016;40(8):1117–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Agrawal N, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154–7.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–82.CrossRefGoogle Scholar
  30. 30.
    Lechner M, et al. Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors. Genome Med. 2013;5(5):49.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Ndiaye C, et al. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol. 2014;15(12):1319–31.PubMedCrossRefGoogle Scholar
  32. 32.
    Miller DL, et al. 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. 2015;185(3):679–92.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Anayannis NV, et al. Epigenetic mechanisms of human papillomavirus-associated head and neck cancer. Arch Pathol Lab Med. 2015;139(11):1373–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Hayes DN, et al. Genetic landscape of human papillomavirus-associated head and neck cancer and comparison to tobacco-related tumors. J Clin Oncol. 2015;33(29):3227–34.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Smeets SJ, et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer. 2007;121(11):2465–72.PubMedCrossRefGoogle Scholar
  36. 36.
    Marur S, et al. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11(8):781–9.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Husain N, Neyaz A. Human papillomavirus associated head and neck squamous cell carcinoma: controversies and new concepts. J Oral Biol Craniofac Res. 2017;7(3):198–205.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Mohan M, Jagannathan N. Oral field cancerization: an update on current concepts. Oncol Rev. 2014;8(1):244.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Nathan CO, et al. Molecular analysis of surgical margins in head and neck squamous cell carcinoma patients. Laryngoscope. 2002;112(12):2129–40.PubMedCrossRefGoogle Scholar
  40. 40.
    Shaw RJ, et al. Molecular staging of surgical margins in oral squamous cell carcinoma using promoter methylation of p16(INK4A), cytoglobin, E-cadherin, and TMEFF2. Ann Surg Oncol. 2013;20(8):2796–802.PubMedCrossRefGoogle Scholar
  41. 41.
    Dasgupta S, et al. Emerging strategies for the early detection and prevention of head and neck squamous cell cancer. J Cell Physiol. 2012;227(2):467–73.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Shakib K, et al. Stem cells in head and neck squamous cell carcinoma. Br J Oral Maxillofac Surg. 2011;49(7):503–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Ferlito A, et al. Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes. Oral Oncol. 2002;38:747–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Arora A, et al. Development of a new outcome prediction model in early-stage squamous cell carcinoma of the oral cavity based on histopathologic parameters with multivariate analysis: the Aditi-Nuzhat Lymph-node Prediction Score (ANLPS) System. Am J Surg Pathol. 2017;41(7):950–60.PubMedCrossRefGoogle Scholar
  45. 45.
    Colella S, et al. Molecular signatures of metastasis in head and neck cancer. Head Neck. 2008;30(10):1273–83.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Nam SW, et al. Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene. 2000;19(2):241–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Yang L, Lin PC. Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression. Semin Cancer Biol. 2017;47:185–95.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Goldenberg D, et al. Intraoperative molecular margin analysis in head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004;130(1):39–44.PubMedCrossRefGoogle Scholar
  49. 49.
    Partridge M, et al. Detection of minimal residual cancer to investigate why oral tumors recur despite seemingly adequate treatment. Clin Cancer Res. 2000;6(7):2718–25.PubMedGoogle Scholar
  50. 50.
    Hamakawa H, et al. Genetic diagnosis of micrometastasis based on SCC antigen mRNA in cervical lymph nodes of head and neck cancer. Clin Exp Metastasis. 1999;17(7):593–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Ferris RL, et al. Molecular staging of cervical lymph nodes in squamous cell carcinoma of the head and neck. Cancer Res. 2005;65(6):2147–56.PubMedCrossRefGoogle Scholar
  52. 52.
    Hwang SJ, et al. Human papillomavirus-related carcinoma with adenoid cystic-like features of the inferior turbinate: a case report. Auris Nasus Larynx. 2015;42(1):53–5.PubMedCrossRefGoogle Scholar
  53. 53.
    Muñoz N, et al. International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348(6):518–27.PubMedCrossRefGoogle Scholar
  54. 54.
    Syrjänen KJ, Pyrhönen S. Demonstration of human papilloma virus (HPV) antigens in a case of urethral condyloma. Scand J Urol Nephrol. 1983;17(3):267–70.PubMedCrossRefGoogle Scholar
  55. 55.
    Bosch FX, et al. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine. 2008;26(Suppl 10):K1–16.PubMedCrossRefGoogle Scholar
  56. 56.
    Stanley M. Pathology and epidemiology of HPV infection in females. Gynecol Oncol. 2010;117(2 Suppl):S5–10.PubMedCrossRefGoogle Scholar
  57. 57.
    Münger K, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004;78(21):11451–60.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Zaravinos A. An updated overview of HPV-associated head and neck carcinomas. Oncotarget. 2014;5(12):3956–69.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Smith EM, et al. Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer. 2004;108(5):766–72.PubMedCrossRefGoogle Scholar
  60. 60.
    Goldenberg D, et al. Cystic lymph node metastasis in patients with head and neck cancer: an HPV-associated phenomenon. Head Neck. 2008;30(7):898–903.PubMedCrossRefGoogle Scholar
  61. 61.
    Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32(7):1044–50.PubMedCrossRefGoogle Scholar
  62. 62.
    Gupta T, et al. Radical radiotherapy with concurrent weekly cisplatin in loco-regionally advanced squamous cell carcinoma of the head and neck: a single-institution experience. Head Neck Oncol. 2009;1:17.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Lassen P, et al. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(12):1992–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Braakhuis BJ, et al. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 2004;96(13):998–1006.PubMedCrossRefGoogle Scholar
  65. 65.
    Smeets SJ, et al. Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus. Oncogene. 2006;25(17):2558–64.PubMedCrossRefGoogle Scholar
  66. 66.
    Singh VS, et al. Do human papilloma viruses play any role in oral squamous cell carcinoma in north Indians? Asian Pac J Cancer Prev. 2015;16(16):7077–84.PubMedCrossRefGoogle Scholar
  67. 67.
    Souza-Rodrígues E, et al. Proteomic analysis of p16ink4a-binding proteins. Proteomics. 2007;7(22):4102–11.PubMedCrossRefGoogle Scholar
  68. 68.
    Pannone G, et al. Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 Immunohistochemistry, Consensus PCR HPV-DNA, and In Situ Hybridization. Infect Agent Cancer. 2012;7:4.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Singhi AD, Westra WH. Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience. Cancer. 2010;116(9):2166–73.PubMedGoogle Scholar
  70. 70.
    Fregonesi PA, et al. p16(INK4A) immunohistochemical overexpression in premalignant and malignant oral lesions infected with human papillomavirus. J Histochem Cytochem. 2003;51(10):1291–7. PubMed PMID: 14500697.PubMedCrossRefGoogle Scholar
  71. 71.
    Marklund L, Hammarstedt L. Impact of HPV in oropharyngeal cancer. J Oncol. 2011;2011:509036.PubMedCrossRefGoogle Scholar
  72. 72.
    Weinberger PM, et al. Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer. Clin Cancer Res. 2004;10(17):5684–91.PubMedCrossRefGoogle Scholar
  73. 73.
    Wenig BM. Lymphoepithelial-like carcinomas of the head and neck. Semin Diagn Pathol. 2015;32(1):74–86.PubMedCrossRefGoogle Scholar
  74. 74.
    Stelow EB, et al. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the nasal cavity, paranasal sinuses and skull base. Head Neck Pathol. 2017;11(1):3–15.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Thompson LDR, Franchi A. New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: nasal cavity, paranasal sinuses and skull base. Virchows Arch. 2018;472(3):315–30.PubMedCrossRefGoogle Scholar
  76. 76.
    Bishop JA, et al. Human papillomavirus-related carcinoma with adenoid cystic-like features: a peculiar variant of head and neck cancer restricted to the sinonasal tract. Am J Surg Pathol. 2013;37(6):836–44.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Wenig BM. Recently described sinonasal tract lesions/neoplasms: considerations for the new world health organization book. Head Neck Pathol. 2014;8(1):33–41.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Bishop JA. Recently described neoplasms of the sinonasal tract. Semin Diagn Pathol. 2016;33(2):62–70.PubMedCrossRefGoogle Scholar
  79. 79.
    Agaimy A, et al. SMARCB1 (INI-1)-deficient sinonasal carcinoma: a series of 39 cases expanding the morphologic and clinicopathologic spectrum of a recently described entity. Am J Surg Pathol. 2017;41(4):458–71.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Agaimy A, et al. SMARCA4-deficient sinonasal carcinoma. Head Neck Pathol. 2017;11(4):541–5.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Rosin MP, et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res. 2000;6(2):357–62.PubMedGoogle Scholar
  82. 82.
    Jiang WW, et al. Accumulative increase of loss of heterozygosity from leukoplakia to foci of early cancerization in leukoplakia of the oral cavity. Cancer. 2001;92(9):2349–56.PubMedCrossRefGoogle Scholar
  83. 83.
    Mao EJ, et al. Loss of heterozygosity at 5q21-22 (adenomatous polyposis coli gene region) in oral squamous cell carcinoma is common and correlated with advanced disease. J Oral Pathol Med. 1998;27(7):297–302.PubMedCrossRefGoogle Scholar
  84. 84.
    Reis PP, et al. Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer. Oncogene. 2002;21(42):6480–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Bockmühl U, et al. Distinct patterns of chromosomal alterations in high- and low-grade head and neck squamous cell carcinomas. Cancer Res. 1996;56(23):5325–9.PubMedGoogle Scholar
  86. 86.
    Baba S, et al. Global DNA hypomethylation suppresses squamous carcinogenesis in the tongue and esophagus. Cancer Sci. 2009;100(7):1186–91.PubMedCrossRefGoogle Scholar
  87. 87.
    Gasche JA, Goel A. Epigenetic mechanisms in oral carcinogenesis. Future Oncol. 2012;8(11):1407–25.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Subbalekha K, et al. Detection of LINE-1s hypomethylation in oral rinses of oral squamous cell carcinoma patients. Oral Oncol. 2009;45(2):184–91.PubMedCrossRefGoogle Scholar
  89. 89.
    Noorlag R, et al. Promoter hypermethylation using 24-gene array in early head and neck cancer: better outcome in oral than in oropharyngeal cancer. Epigenetics. 2014;9(9):1220–7.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Clausen MJ, et al. Identification and validation of WISP1 as an epigenetic regulator of metastasis in oral squamous cell carcinoma. Genes Chromosomes Cancer. 2016;55(1):45–59.PubMedCrossRefGoogle Scholar
  91. 91.
    Zuo C, et al. O6-methylguanine-DNA methyltransferase gene: epigenetic silencing and prognostic value in head and neck squamous cell carcinoma. Cancer Epidemiol. 2004;13(6):967–75.Google Scholar
  92. 92.
    Wilson GA, et al. Integrated virus-host methylome analysis in head and neck squamous cell carcinoma. Epigenetics. 2013;8(9):953–61.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Sartor MA, et al. Genome-wide methylation and expression differences in HPV(+) and HPV(-) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis. Epigenetics. 2011;6(6):777–87.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Holland D, et al. Activation of the enhancer of zeste homologue 2 gene by the human papillomavirus E7 oncoprotein. Cancer Res. 2008;68(23):9964–72.PubMedCrossRefGoogle Scholar
  95. 95.
    McCabe MT, et al. Cancer DNA methylation: molecular mechanisms and clinical implications. Clin Cancer Res. 2009;15(12):3927–37.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Maruya S, et al. Differential methylation status of tumor-associated genes in head and neck squamous carcinoma: incidence and potential implications. Clin Cancer Res. 2004;10(11):3825–30.PubMedCrossRefGoogle Scholar
  97. 97.
    Carreras-Torras C, Gay-Escoda C. Techniques for early diagnosis of oral squamous cell carcinoma: systematic review. Med Oral Patol Oral Cir Bucal. 2015;20(3):e305–15.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Khan H, et al. Correlation between expressions of Cyclin-D1, EGFR and p53 with chemoradiation response in patients of locally advanced oral squamous cell carcinoma. BBA Clin. 2014;3:11–7.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Schantz SPHL, Forastiere A. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 797–860.Google Scholar
  100. 100.
    Siu LL, et al. Princess Margaret Hospital Phase II Consortium; National Cancer Institute of Canada Clinical Trials Group Study. Phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Princess Margaret Hospital phase II consortium and National Cancer Institute of Canada Clinical Trials Group Study. J Clin Oncol. 2007;25(16):2178–83.PubMedCrossRefGoogle Scholar
  101. 101.
    Kim ES, et al. Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer. Presented at the American Society of Clinical Oncology Annual Meeting, June 1–5, 2007, Chicago.Google Scholar
  102. 102.
    Del Campo JM, et al. Effects of lapatinib monotherapy: results of a randomised phase II study in therapy-naive patients with locally advanced squamous cell carcinoma of the head and neck. Br J Cancer. 2011;105(5):618–27.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    de Souza JA, et al. A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 2012;18(8):2336–43.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Patel PN, et al. Efficacy and toxicity of gefitinib in palliative treatment in recurrent squamous cell carcinoma of head and neck in poor performance elderly patients. Presented at the European Society of Medical Oncology Congress, September 29, 2014, Madrid.Google Scholar
  105. 105.
    Argiris A, et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013;31:1405–14.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Machiels JP, et al. LUX-H&N 1 investigators. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015;16(5):583–94.PubMedCrossRefGoogle Scholar
  107. 107.
    Cohen EEW, et al. Biomarker analysis in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients (pts) treated with second-line afatinib versus methotrexate (MTX): LUX-Head and Neck 1 (LUX-H&N1). Presented at the American Society of Clinical Oncology Annual Meeting, May 29–June 2, 2015, Chicago.Google Scholar
  108. 108.
    Machiels JP, et al. Activity of afatinib administered in a window pre-operative study in squamous cell carcinoma of the head and neck (SCCHN): EORTC-90111. Presented at the American Society of Clinical Oncology Annual Meeting, June 3–7, 2016, Chicago.Google Scholar
  109. 109.
    Abdul Razak AR, et al. A phase II trial of dacomitinib, an oral pan-human EGF receptor (HER) inhibitor, as first-line treatment in recurrent and/or metastatic squamous-cell carcinoma of the head and neck. Ann Oncol. 2013;24:761–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Bonner JA, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.PubMedCrossRefGoogle Scholar
  111. 111.
    Bonner JA, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Burtness B, et al. Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23(34):8646–54. Erratum in: J Clin Oncol. 2006;24(4):724.PubMedCrossRefGoogle Scholar
  113. 113.
    Yang XD, et al. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001;38(1):17–23.PubMedCrossRefGoogle Scholar
  114. 114.
    Wirth LJ, et al. PARTNER: an open-label, randomized, phase 2 study of docetaxel/cisplatin chemotherapy with or without panitumumab as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck. Oral Oncol. 2016;61:31–40.PubMedCrossRefGoogle Scholar
  115. 115.
    Machiels JP, et al. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Lancet Oncol. 2011;12(4):333–43.PubMedCrossRefGoogle Scholar
  116. 116.
    Eriksen JG, et al. DAHANCA 19: first results of a randomized phase III study of the importance of the EGFR-inhibitor zalutumumab for the outcome of primary curative radiotherapy for squamous cell carcinoma of the head and neck. Late breaking abstract presented at: the European Cancer Congress, September 27–October 1, 2013, Amsterdam, Netherlands. Abstract 12.Google Scholar
  117. 117.
    Rodriguez MO, et al. Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck. Cancer Biol Ther. 2010;9(5):343–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Basavaraj C, et al. Nimotuzumab with chemoradiation confers a survival advantage in treatment-naive head and neck tumors over expressing EGFR. Cancer Biol Ther. 2010;10(7):673–81.PubMedCrossRefGoogle Scholar
  119. 119.
    Uno M, et al. Anti-HER2-antibody enhances irradiation-induced growth inhibition in head and neck carcinoma. Int J Cancer. 2001;94(4):474–9.PubMedCrossRefGoogle Scholar
  120. 120.
    Pollock NI, Grandis JR. HER2 as a therapeutic target in head and neck squamous cell carcinoma. Clin Cancer Res. 2015;21(3):526–33.PubMedCrossRefGoogle Scholar
  121. 121.
    Cohen EE, et al. Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study. Lancet Oncol. 2009;10(3):247–57.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Cohen R, et al. Bevacizumab and surgery: what is the real risk? Future Oncol. 2009;5(7):915–7.PubMedCrossRefGoogle Scholar
  123. 123.
    Williamson SK, et al. A phase II trial of sorafenib in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC): a Southwest Oncology Group (SWOG) trial. 2007 ASCO Annual Meeting Proceedings Part I. J Clin Oncol. 2007;25(18S):6044.Google Scholar
  124. 124.
    Choong NW, et al. Phase II study of sunitinib malate in head and neck squamous cell carcinoma. Invest New Drugs. 2010;28(5):677–83.PubMedCrossRefGoogle Scholar
  125. 125.
    Machiels JP, et al. Phase II study of sunitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: GORTEC 2006-01. J Clin Oncol. 2010;28(1):21–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Limaye S, et al. A randomized phase II study of docetaxel with or without vandetanib in recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN). Oral Oncol. 2013;49:835–41.PubMedCrossRefGoogle Scholar
  127. 127.
    Fung C, Grandis JR. Emerging drugs to treat squamous cell carcinomas of the head and neck. Expert Opin Emerg Drugs. 2010;15(3):355–73.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Brooks HD, et al. Phase II study of dasatinib in the treatment of head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2009;27(Suppl):15s. Abstract 6022.Google Scholar
  129. 129.
    Johnson FM, et al. Phase 1 pharmacokinetic and drug-interaction study of dasatinib in patients with advanced solid tumors. Cancer. 2010;116(6):1582–91.PubMedCrossRefGoogle Scholar
  130. 130.
    Aissat N, et al. Antiproliferative effects of rapamycin as a single agent and in combination with carboplatin and paclitaxel in head and neck cancer cell lines. Cancer Chemother Pharmacol. 2008;62(2):305–13.PubMedCrossRefGoogle Scholar
  131. 131.
    Uppaluri R, et al. Immunotherapy with pembrolizumab in surgically resectable. Presented at the American Society of Clinical Oncology Annual Meeting, June 3–7, 2016, Chicago.Google Scholar
  132. 132.
    Mehra R, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): pooled analyses after long-term follow-up in KEYNOTE-012. Presented at the American Society of Clinical Oncology Annual Meeting, June 3–7, 2016, Chicago.Google Scholar
  133. 133.
    Ferris RL, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Seiwert T, et al. A phase 3, randomized, open-label study of first-line durvalumab (MEDI4736) ± tremelimumab versus standard of care (SoC; EXTREME regimen) in recurrent/metastatic (R/M) SCCHN: KESTREL. Presented at the 2016 American Society of Clinical Oncology Annual Meeting, June 3–7, 2016, Chicago.Google Scholar
  135. 135.
    Economopoulou P, et al. The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches. ESMO Open. 2017;1(6):e000122.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    Chow LQM, et al. Phase Ib trial of TLR8 agonist VTX-2237 in combination with cetuximab in patients with recurrent or metastatic squamous cell carcinomas of the head and neck (SCCHN). Presented at the Multidisciplinary Head and Neck Cancer Symposium, 20–22 Feb 2014, Scottsdale.Google Scholar
  137. 137.
    Chow LQM, et al. Phase Ib trial of the toll-like receptor 8 agonist, motolimod (VTX-2337), combined with cetuximab in patients with recurrent or metastatic SCCHN. Clin Cancer Res. 2017;23(10):2442–50.PubMedCrossRefGoogle Scholar
  138. 138.
    Chung CH, et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell. 2004;5(5):489–500.PubMedCrossRefGoogle Scholar
  139. 139.
    Vermorken JB, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.PubMedCrossRefGoogle Scholar
  140. 140.
    Ferrara N, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391–400.PubMedCrossRefGoogle Scholar
  141. 141.
    Stein MN, Flaherty KT. CCR drug updates: sorafenib and sunitinib in renal cell carcinoma. Clin Cancer Res. 2007;13(13):3765–70.PubMedCrossRefGoogle Scholar
  142. 142.
    Chow LQM, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol. 2016;34(32):3838–45.PubMedCrossRefGoogle Scholar
  143. 143.
    Seiwert TY, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17(7):956–65.PubMedCrossRefGoogle Scholar
  144. 144.
    Gold B, et al. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology. J Mol Diagn. 2015;17:209–24.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Ignatiadis M, Dawson SJ. Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? Ann Oncol. 2014;25:2304–13.PubMedCrossRefGoogle Scholar
  146. 146.
    Husain, et al. Comparison of circulating cell-free DNA in serum as a biomarker for diagnosis and therapy monitoring in spectrum of tumors. Abstracts and Case Studies From the College of American Pathologists 2017 Annual Meeting (CAP17). Arch Pathol Lab Med. 2017;141(9):e2–191.CrossRefGoogle Scholar
  147. 147.
    Mazurek AM, et al. Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV detection in plasma. Cancer Biomark. 2013;13(5):385–94.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Nuzhat Husain
    • 1
  • Azfar Neyaz
    • 1
  1. 1.Department of PathologyDr. Ram Manohar Lohia Institute of Medical SciencesLucknowIndia

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