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Molecular Diagnostics in Head and Neck Squamous Cell Carcinoma

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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.

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References

  1. Parkin DM, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  4. Byakodi R, et al. Oral cancer in India: an epidemiologic and clinical review. J Community Health. 2012;37(2):316–9.

    Article  PubMed  Google Scholar 

  5. Amin MB, et al. AJCC cancer staging manual. 8th ed. New York: Springer; 2017.

    Book  Google Scholar 

  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. Gupta S, et al. Understanding molecular markers in recurrent oral squamous cell carcinoma treated with chemoradiation. Heliyon. 2016;2(12):e00206. eCollection 2016 Dec.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Levine AJ, et al. The p53 tumour suppressor gene. Nature. 1991;351(6326):453–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  10. Soussi T, Wiman KG. Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell. 2007;12(4):303–12.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  15. Gillison ML, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307(7):693–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  22. Wenig BM. Squamous cell carcinoma of the upper aerodigestive tract: dysplasia and select variants. Mod Pathol. 2017;30(s1):S112–8.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Ang KK, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–82.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Anayannis NV, et al. Epigenetic mechanisms of human papillomavirus-associated head and neck cancer. Arch Pathol Lab Med. 2015;139(11):1373–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  36. Marur S, et al. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11(8):781–9.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Mohan M, Jagannathan N. Oral field cancerization: an update on current concepts. Oncol Rev. 2014;8(1):244.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Nathan CO, et al. Molecular analysis of surgical margins in head and neck squamous cell carcinoma patients. Laryngoscope. 2002;112(12):2129–40.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shakib K, et al. Stem cells in head and neck squamous cell carcinoma. Br J Oral Maxillofac Surg. 2011;49(7):503–6.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  45. Colella S, et al. Molecular signatures of metastasis in head and neck cancer. Head Neck. 2008;30(10):1273–83.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  47. Yang L, Lin PC. Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression. Semin Cancer Biol. 2017;47:185–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Goldenberg D, et al. Intraoperative molecular margin analysis in head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004;130(1):39–44.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  56. Stanley M. Pathology and epidemiology of HPV infection in females. Gynecol Oncol. 2010;117(2 Suppl):S5–10.

    Article  PubMed  Google Scholar 

  57. Münger K, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004;78(21):11451–60.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  58. Zaravinos A. An updated overview of HPV-associated head and neck carcinomas. Oncotarget. 2014;5(12):3956–69.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  67. Souza-Rodrígues E, et al. Proteomic analysis of p16ink4a-binding proteins. Proteomics. 2007;7(22):4102–11.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  71. Marklund L, Hammarstedt L. Impact of HPV in oropharyngeal cancer. J Oncol. 2011;2011:509036.

    Article  PubMed  Google Scholar 

  72. Weinberger PM, et al. Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer. Clin Cancer Res. 2004;10(17):5684–91.

    Article  CAS  PubMed  Google Scholar 

  73. Wenig BM. Lymphoepithelial-like carcinomas of the head and neck. Semin Diagn Pathol. 2015;32(1):74–86.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Bishop JA. Recently described neoplasms of the sinonasal tract. Semin Diagn Pathol. 2016;33(2):62–70.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Agaimy A, et al. SMARCA4-deficient sinonasal carcinoma. Head Neck Pathol. 2017;11(4):541–5.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  86. Baba S, et al. Global DNA hypomethylation suppresses squamous carcinogenesis in the tongue and esophagus. Cancer Sci. 2009;100(7):1186–91.

    Article  CAS  PubMed  Google Scholar 

  87. Gasche JA, Goel A. Epigenetic mechanisms in oral carcinogenesis. Future Oncol. 2012;8(11):1407–25.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  92. Wilson GA, et al. Integrated virus-host methylome analysis in head and neck squamous cell carcinoma. Epigenetics. 2013;8(9):953–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  95. McCabe MT, et al. Cancer DNA methylation: molecular mechanisms and clinical implications. Clin Cancer Res. 2009;15(12):3927–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Schantz SPHL, Forastiere A. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 797–860.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Cohen R, et al. Bevacizumab and surgery: what is the real risk? Future Oncol. 2009;5(7):915–7.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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. Ferris RL, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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. Economopoulou P, et al. The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches. ESMO Open. 2017;1(6):e000122.

    Article  PubMed  PubMed Central  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  139. Vermorken JB, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  141. Stein MN, Flaherty KT. CCR drug updates: sorafenib and sunitinib in renal cell carcinoma. Clin Cancer Res. 2007;13(13):3765–70.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Ignatiadis M, Dawson SJ. Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? Ann Oncol. 2014;25:2304–13.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

Disclosure of funding: None.

Conflict of interest: None.

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  1. Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

    Nuzhat Husain & Azfar Neyaz

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  1. Nuzhat Husain
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  1. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India

    Kamla Kant Shukla

  2. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India

    Praveen Sharma

  3. Department of Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, India

    Sanjeev Misra

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Husain, N., Neyaz, A. (2019). Molecular Diagnostics in Head and Neck Squamous Cell Carcinoma. In: Shukla, K., Sharma, P., Misra, S. (eds) Molecular Diagnostics in Cancer Patients. Springer, Singapore. https://doi.org/10.1007/978-981-13-5877-7_11

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