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Human Papillomavirus (HPV) Biomarkers in Head and Neck: Squamous Cell Carcinoma (HNSCC)

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Abstract

Head and cell neck squamous carcinomas are a heterogeneous group of neoplasms evolved through multistep carcinogenesis, which is commonly attributed to the abuse of tobacco and alcohol. The epidemiological and molecular evidences from recent decades show the human papillomavirus (HPV) to be causative in a subset of HNSCC. Anatomically, HPV exhibits a predilection for the oral cavity and oropharyngeal and laryngeal regions of the head and neck. HPV-positive and HPV-negative tumors differ in many facets that include histology, differentiation, risk factors, and prognosis. At present, no guidelines are available to choose an appropriate biomarker for the clinical assessment of HPV in HNSCC malignancies. Currently, p16 immunohistochemistry is used as a potential surrogate marker, but its use as a predictive marker is still questionable. Taking the present scenario into consideration, we present in this chapter a list of biomolecules that have higher possibility for use as biomarkers. A randomized clinical trial is required for validation of each biomolecule before designating it as a biomarker that can be subsumed for routine analysis.

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Abbreviations

APC:

Adenomatous Polyposis Coli

ATP:

Adenosine Triphosphate

BER:

Base Excision Repair

CDC:

Centers for Disease Control and Prevention

CH1:

Cysteine/Histidine-Rich 1

CI:

Confidence Interval

DNA:

Deoxyribonucleic Acid

EGFR:

Epidermal Growth Factor Receptor

FDA:

Food and Drug Administration

HLA:

Human Leukocyte Antigen

HNSCC:

Head and Neck Squamous Cell Carcinoma

HPV:

Human Papillomavirus

hTERT:

Human Telomerase Reverse Transcriptase

ISH:

In Situ Hybridization

KRT14:

Human Keratin 14

LCR:

Long Control Region

MCM7:

Minimicrosome Protein 7

MDM2:

Mouse Double Minute 2 Homolog

MHC:

Major Histocompatibility Complex

mMU:

Milli-Merk Units

MPG:

Multiplex Human Papillomavirus Genotyping

OPSCC:

Oropharyngeal Squamous Cell Carcinoma

OR:

Odds Ratio

OSCC:

Oral Squamous Cell Carcinoma

PDCD4:

Programmed Cell Death Protein 4

PSCC:

Pharyngeal Squamous Cell Carcinoma

Rb:

Retinoblastoma

RNA:

Ribonucleic Acid

RTOG:

Radiation Therapy Oncology Group

RT-qPCR:

Reverse Transcription Quantitative Polymerase Chain Reaction

SSB:

Single-Strand Break

TGF:

Transforming Growth Factor

TGFBR3:

TGF Beta-Receptor 3

TIL:

Tumor-Infiltrating Lymphocytes

VLP:

Viruslike Particles

XRCC1:

X-ray Repair Cross-Complementing Protein 1

References

  • Abeloff MD, Armitage J, Niederhuber JE, Kastan MB, et al. Abeloff’s clinical oncology. 4th ed. Philadelphia: Elsevier; 2009.

    Google Scholar 

  • Agoston ES, Robinson SJ, Mehra KK, et al. Polymerase chain reaction detection of HPV in squamous carcinoma of the oropharynx. Am J Clin Pathol. 2010;134:36–41.

    Article  PubMed  Google Scholar 

  • Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ang MK, Patel MR, Yin XY, et al. High XRCC1 protein expression is associated with poorer survival in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2011;17:6542–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atkinson AJ, Colburn WA, DeGruttola VG, et al. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.

    Article  Google Scholar 

  • Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  • Blow JJ. Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor. J Cell Biol. 1993;122:993–1002.

    Article  CAS  PubMed  Google Scholar 

  • Bussu F, Sali M, Gallus R, et al. HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker? Br J Cancer. 2013;108:1157–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene. 2008;27:5869–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaturvedi AK, Engels EA, Anderson WF, et al. Incidence trends for human papillomavirus-related (HPV-R) and unrelated (HPV-U) head and neck squamous cell carcinomas (HNSCC) in the United States (US). J Clin Oncol. 2007;25:6001.

    Google Scholar 

  • Chen X, Sturgis EM, Lei D, et al. Human papillomavirus seropositivity synergizes with MDM2 variants to increase the risk of oral squamous cell carcinoma. Cancer Res. 2010;70:7199–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • D’Souza G, Sugar E, Ruby W, et al. Analysis of the effect of DNA purification on detection of human papillomavirus in oral rinse samples by PCR. J Clin Microbiol. 2005;43:5526–35.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dayyani F, Etzel CJ, Liu M, et al. Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol. 2010;2:15.

    Article  PubMed  PubMed Central  Google Scholar 

  • de Villiers EM, Fauquet C, Broker TR, et al. Classification of papillomaviruses. Virology. 2004;324:17–27.

    Article  PubMed  Google Scholar 

  • Ernoux-Neufcoeur P, Arafa M, Decaestecker C, et al. Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma. J Cancer Res Clin Oncol. 2011;137:173–81.

    Article  CAS  PubMed  Google Scholar 

  • Fountzilas G, Kalogera-Fountzila A, Lambaki S, et al. MMP9 but not EGFR, MET, ERCC1, P16, and P-53 is associated with response to concomitant radiotherapy, cetuximab, and weekly cisplatin in patients with locally advanced head and neck cancer. J Oncol. 2009;2009:305908.

    Article  PubMed  PubMed Central  Google Scholar 

  • Freedman DA, Levine AJ. Regulation of the p53 protein by the MDM2 oncoprotein – thirty-eighth G.H.A. Clowes Memorial Award Lecture. Cancer Res. 1999;59:1–7.

    CAS  PubMed  Google Scholar 

  • Furniss CS, McClean MD, Smith JF, et al. Human papillomavirus 16 and head and neck squamous cell carcinoma. Int J Cancer. 2007;120:2386–92.

    Article  CAS  PubMed  Google Scholar 

  • Gao G, Chernock RD, Gay HA, et al. A novel RT-PCR method for quantification of human papillomavirus transcripts in archived tissues and its application in oropharyngeal cancer prognosis. Int J Cancer. 2013;132:882–90.

    Article  CAS  PubMed  Google Scholar 

  • Gillison ML. Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination. J Adolesc Health. 2008;43:S52–60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gillison ML, Alemany L, Snijders PJ, et al. Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis. Vaccine. 2012;30:F34–54.

    Article  PubMed  Google Scholar 

  • Hafkamp HC, Speel EJ, Haesevoets A, et al. A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5–8. Int J Cancer. 2003;107:394–400.

    Article  CAS  PubMed  Google Scholar 

  • Hafkamp HC, Mooren JJ, Claessen SM, et al. P21 Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis. Mod Pathol. 2009;22:686–98.

    Article  CAS  PubMed  Google Scholar 

  • Harrison LBS, Roy B, Waun Ki Hong, editors. Head and neck cancer: a multidisciplinary approach. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2009.

    Google Scholar 

  • Hoffmann M, Tribius S, Quabius ES, et al. HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer – how valid is p16INK4A as surrogate marker? Cancer Lett. 2012;323:88–96.

    Article  CAS  PubMed  Google Scholar 

  • Hui AB, Lin A, Xu W, et al. Potentially prognostic miRNAs in HPV-associated oropharyngeal carcinoma. Clin Cancer Res. 2013;19:2154–62.

    Article  CAS  PubMed  Google Scholar 

  • IARC. IARC monographs on the evaluation of carcinogenic risks to humans human papillomaviruses. Lyon: IARC; 2007.

    Google Scholar 

  • Jemal A, Murray T, Samuels A, et al. Cancer statistics, 2003. CA Cancer J Clin. 2003;53:5–26.

    Article  PubMed  Google Scholar 

  • Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature. 1996;380:79–82.

    Article  CAS  PubMed  Google Scholar 

  • Kreimer AR, Clifford GM, Boyle P, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467–75.

    Article  CAS  PubMed  Google Scholar 

  • Kuhne C, Banks L. E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box. J Biol Chem. 1998;273:34302–9.

    Article  CAS  PubMed  Google Scholar 

  • Lajer CB, Nielsen FC, Friis-Hansen L, et al. Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study. Br J Cancer. 2011;104:830–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lajer CB, Garnaes E, Friis-Hansen L, et al. 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. 2012;106:1526–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li C, Johnson DE. Liberation of functional p53 by proteasome inhibition in human papilloma virus-positive head and neck squamous cell carcinoma cells promotes apoptosis and cell cycle arrest. Cell Cycle. 2013;12:923–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McLemore MS, Haigentz Jr M, Smith RV, et al. Head and neck squamous cell carcinomas in HIV-positive patients: a preliminary investigation of viral associations. Head Neck Pathol. 2010;4:97–105.

    Article  PubMed  PubMed Central  Google Scholar 

  • Munger K, Basile JR, Duensing S, et al. Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene. 2001;20:7888–98.

    Article  CAS  PubMed  Google Scholar 

  • Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348:518–27.

    Article  PubMed  Google Scholar 

  • Nasman A, Romanitan M, Nordfors C, et al. Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS One. 2012;7:e38711.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nedergaard BS, Ladekarl M, Thomsen HF, et al. Low density of CD3+, CD4+ and CD8+ cells is associated with increased risk of relapse in squamous cell cervical cancer. Br J Cancer. 2007;97:1135–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nichols AC, Palma DA, Dhaliwal SS, et al. The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population. Curr Oncol. 2013;20:212–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Rorke MA, Ellison MV, Murray LJ, et al. Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. Oral Oncol. 2012;48:1191–201.

    Article  PubMed  Google Scholar 

  • Perez-Ordonez B, Beauchemin M, Jordan RC. Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol. 2006;59:445–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Psyrri A, Sasaki C, Vassilakopoulou M, et al. Future directions in research, treatment and prevention of HPV-related squamous cell carcinoma of the head and neck. Head Neck Pathol. 2012;6:S121–8.

    Article  PubMed  Google Scholar 

  • Ramdas L, Giri U, Ashorn CL, et al. miRNA expression profiles in head and neck squamous cell carcinoma and adjacent normal tissue. Head Neck. 2009;31:642–54.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ribeiro KB, Levi JE, Pawlita M, et al. Low human papillomavirus prevalence in head and neck cancer: results from two large case–control studies in high-incidence regions. Int J Epidemiol. 2011;40:489–502.

    Article  PubMed  Google Scholar 

  • Rieckmann T, Tribius S, Grob TJ, et al. HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Radiother Oncol. 2013;107:242–6.

    Article  CAS  PubMed  Google Scholar 

  • Salazar CR, Smith RV, Garg MK, et al. Human papillomavirus-associated head and neck squamous cell carcinoma survival: a comparison by tumor site and initial treatment. Head Neck Pathol. 2014;8:77–87.

    Google Scholar 

  • Shin MK, Pitot HC, Lambert PF. Pocket proteins suppress head and neck cancer. Cancer Res. 2006;72:1280–9.

    Article  Google Scholar 

  • 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;116:2166–73.

    PubMed  Google Scholar 

  • Strati K, Pitot HC, Lambert PF. Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model. Proc Natl Acad Sci U S A. 2006;103:14152–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Syrjanen S. The role of human papillomavirus infection in head and neck cancers. Ann Oncol. 2010;21:vii243–5.

    Article  PubMed  Google Scholar 

  • Syrjanen KJ, Pyrhonen S, Syrjanen SM, et al. Immunohistochemical demonstration of human papilloma virus (HPV) antigens in oral squamous cell lesions. Br J Oral Surg. 1983;21:147–53.

    Article  CAS  PubMed  Google Scholar 

  • Talmadge JE, Donkor M, Scholar E. Inflammatory cell infiltration of tumors: Jekyll or Hyde. Cancer Metastasis Rev. 2007;26:373–400.

    Article  PubMed  Google Scholar 

  • Thomas GR, Nadiminti H, Regalado J. Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol. 2005;86:347–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thommes P, Kubota Y, Takisawa H, et al. The RLF-M component of the replication licensing system forms complexes containing all six MCM/P1 polypeptides. EMBO J. 1997;16:3312–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–10.

    Article  CAS  PubMed  Google Scholar 

  • Weaver DA, Crawford EL, Warner KA, et al. ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines. Mol Cancer. 2005;4:18.

    Article  PubMed  PubMed Central  Google Scholar 

  • Westra WH. The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol. 2009;3:78–81.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xie X, Piao L, Cavey GS, et al. Phosphorylation of Nanog is essential to regulate Bmi1 and promote tumorigenesis. Oncogene. 2014;33:2040–52.

    Google Scholar 

  • Yie SM, Yang H, Ye SR, et al. Expression of HLA-G is associated with prognosis in esophageal squamous cell carcinoma. Am J Clin Pathol. 2007;128:1002–9.

    Article  PubMed  Google Scholar 

  • Zhao M, Rosenbaum E, Carvalho AL, et al. Feasibility of quantitative PCR-based saliva rinse screening of HPV for head and neck cancer. Int J Cancer. 2005;117:605–10.

    Article  CAS  PubMed  Google Scholar 

  • zur Hausen H. Papillomavirus infections – a major cause of human cancers. Biochim Biophys Acta. 1996;1288:F55–78.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, LSU Health Shreveport, Shreveport, LA, USA

    Arunkumar Anandharaj, Oleksandr Ekshyyan, Tara Moore-Medlin, Vikas Mehta & Cherie-Ann O. Nathan

Authors
  1. Arunkumar Anandharaj
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  2. Oleksandr Ekshyyan
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  3. Tara Moore-Medlin
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  4. Vikas Mehta
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  5. Cherie-Ann O. Nathan
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Corresponding author

Correspondence to Cherie-Ann O. Nathan .

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Editors and Affiliations

  1. Faculty of Life Sciences & Medicine King’s College London, Department of Nutrition and Dietetics Division of Diabetes & Nutritional Scien, London, United Kingdom

    Victor R. Preedy

  2. Faculty of Science & Technology, Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Anandharaj, A., Ekshyyan, O., Moore-Medlin, T., Mehta, V., Nathan, CA.O. (2015). Human Papillomavirus (HPV) Biomarkers in Head and Neck: Squamous Cell Carcinoma (HNSCC). In: Preedy, V., Patel, V. (eds) Biomarkers in Cancer. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7681-4_31

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