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Roles of Human Papillomaviruses and p16 in Oral Cancer

  • Sritippho, Thanun (Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University) ;
  • Chotjumlong, Pareena (Center of Excellence in Oral and Maxillofacial Biology, Faculty of Dentistry, Chiang Mai University) ;
  • Iamaroon, Anak (Center of Excellence in Oral and Maxillofacial Biology, Faculty of Dentistry, Chiang Mai University)
  • Published : 2015.10.06

Abstract

Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationship between human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, a tumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker for HPV infection in head and neck cancer.

Keywords

HPV;p16;oral squamous cell carcinoma

References

  1. Aggarwal S, Devaraja K, Sharma SC, et al (2014). Expression of vascular endothelial growth factor (VEGF) in patients with oral squamous cell carcinoma and its clinical significance. Clinica Chimica Acta, 436, 35-40. https://doi.org/10.1016/j.cca.2014.04.027
  2. Akiba S, Olthof NC, Speel E-JM, et al (2014). Comprehensive analysis of HPV16 integration in OSCC reveals no significant impact of physical status on viral oncogene and virally disrupted human gene expression. PLoS One, 9, 88718. https://doi.org/10.1371/journal.pone.0088718
  3. American Cancer Society (2014). Cancer facts & figures 2014, atlanta, american cancer society.
  4. Antonsson A, Neale RE, Boros S, et al (2015). Human papillomavirus status and p16(INK4A) expression in patients with mucosal squamous cell carcinoma of the head and neck in Queensland, Australia. Cancer Epidemiol, 39, 174-81. https://doi.org/10.1016/j.canep.2015.01.010
  5. Bixofis RB, Sassi LM, Patussi C, et al (2014). Significance of p16 positive expression in oropharyngeal cancers. Asian Pac J Cancer Prev, 15, 10289-92.
  6. Bussu F, Sali M, Gallus R, et al (2014). Human papillomavirus (HPV) infection in squamous cell carcinomas arising from the oropharynx: detection of HPV DNA and p16 immunohistochemistry as diagnostic and prognostic indicators--a pilot study. Int J Radiat Oncol Biol Phys, 89, 1115-20. https://doi.org/10.1016/j.ijrobp.2014.04.044
  7. Cao F, Zhang W, Zhang F, et al (2014). Prognostic significance of high-risk human papillomavirus and p16(INK4A) in patients with esophageal squamous cell carcinoma. Int J Clin Exp Med, 7, 3430-8.
  8. Chandarana SP, Lee JS, Chanowski EJP, et al (2013). Prevalence and predictive role of p16 and epidermal growth factor receptor in surgically treated oropharyngeal and oral cavity cancer. Head Neck, 35, 1083-90. https://doi.org/10.1002/hed.23087
  9. Choi S, Myers JN (2008). Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res, 87, 14-32. https://doi.org/10.1177/154405910808700104
  10. Chung CH, Zhang Q, Kong CS, et al (2014). p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clin Oncol, 32, 3930-8. https://doi.org/10.1200/JCO.2013.54.5228
  11. Cohen RF, Contrino J, Spiro JD, et al (1995). Interleukin-8 expression by head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg, 121, 202-9. https://doi.org/10.1001/archotol.1995.01890020064013
  12. D'Souza G, Dempsey A (2011). The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med, 53 5-11. https://doi.org/10.1016/j.ypmed.2011.08.001
  13. Devi P (2004). Basics of carcinogenesis. Health Adm, 17, 16-24.
  14. Dragomir LP, Simionescu C, Margaritescu C, et al (2012). P53, p16 and Ki67 immunoexpression in oral squamous carcinomas. Rom J Morphol Embryol, 53, 89-93.
  15. Elango KJ, Suresh A, Erode EM, et al (2011). Role of human papilloma virus in oral tongue squamous cell carcinoma. Asian Pac J Cancer Prev, 12, 889-96.
  16. Fang KH, Kao HK, Cheng MH, et al (2009). Histological differentiation of primary oral squamous cell carcinomas in an area of betel quid chewing prevalence. Otolaryngol Head Neck Surg, 141, 743-9. https://doi.org/10.1016/j.otohns.2009.09.012
  17. Fregonesi PA, Teresa DB, Duarte RA, et al (2003). p16(INK4A) immunohistochemical overexpression in premalignant and malignant oral lesions infected with human papillomavirus. J Histochem Cytoc, 51, 1291-7. https://doi.org/10.1177/002215540305101006
  18. Gan L-L, Zhang H, Guo J-H, et al (2014). Prevalence of human papillomavirus infection in oral squamous cell carcinoma: a case-control Study in Wuhan, China. Asian Pac J Cancer Prev, 15, 5861-5. https://doi.org/10.7314/APJCP.2014.15.14.5861
  19. Geissler C, Tahtali A, Diensthuber M, et al (2013). The role of p16 expression as a predictive marker in HPV-positive oral SCCHN--a retrospective single-center study. Anticancer Res, 33, 913-6.
  20. Giraldi G, Martinoli L, De Luca d'Alessandro E (2014). The human papillomavirus vaccination: a review of the costeffectiveness studies. Clin Ter, 165, 426-32.
  21. Gonzales-Moles MA, Rodriguez-Archilla A, Ruiz-Avila I, et al (2002). p16 Expression in squamous carcinomas of the tongue. Onkologie, 25, 433-6. https://doi.org/10.1159/000067437
  22. Hanahan D, Weinberg RA (2000). The hallmarks of cancer. Cell, 100, 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
  23. Iamaroon A, Pattanaporn K, Pongsiriwet S, et al (2004). Analysis of 587 cases of oral squamous cell carcinoma in northern Thailand with a focus on young people. Int J Oral Maxillofac Surg, 33, 84-8. https://doi.org/10.1054/ijom.2003.0503
  24. Johnson N JP, Amarasinghe A (2011). Squamous cell carcinoma and precursor lesions of the oral cavity: epidemiology and aetiology. Periodontol, 57, 19-37. https://doi.org/10.1111/j.1600-0757.2011.00401.x
  25. Kanao H, Enomoto T, Ueda Y, et al (2004). Correlation between p14(ARF)/p16(INK4A) expression and HPV infection in uterine cervical cancer. Cancer Lett, 213, 31-7. https://doi.org/10.1016/j.canlet.2004.03.030
  26. Kapoor P, Deshmukh RS (2012). VEGF: A critical driver for angiogenesis and subsequent tumor growth: An IHC study. J Oral Max Pathol, 16, 330-7. https://doi.org/10.4103/0973-029X.102478
  27. Kim KS, Park SA, Ko KN, et al (2014). Current status of human papillomavirus vaccines. Clin Exp Vaccine Res, 3, 168-75. https://doi.org/10.7774/cevr.2014.3.2.168
  28. Kim S-K, Park S-G, Kim K-W (2015). Expression of vascular endothelial growth factor in oral squamous cell carcinoma. J Korean Associa Oral Max Surg, 41, 11-8. https://doi.org/10.5125/jkaoms.2015.41.1.11
  29. Kreimer AR (2014). Prospects for prevention of HPV-driven oropharynx cancer. Oral Oncol, 50, 555-9. https://doi.org/10.1016/j.oraloncology.2013.06.007
  30. Kreimer AR, Clifford GM, Boyle P, et al (2005). Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev, 14, 467-75. https://doi.org/10.1158/1055-9965.EPI-04-0551
  31. Krisanaprakornkit S, Iamaroon A (2012). Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma. ISRN Oncol, 2012, 1-10.
  32. Kumar S, Biswas M, Jose T (2015). HPV vaccine: Current status and future directions. Med J Armed Forces India, 71, 171-7. https://doi.org/10.1016/j.mjafi.2015.02.006
  33. Kumar V, Abbas AK, Fausto N, et al (2010). Robbins & Cotran Pathologic Basis of Disease, Philadelphia, USA, Elsevires Inc.
  34. Laco J, Nekvindova J, Novakova V, et al (2012). Biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral and oropharyngeal squamous cell carcinoma, with emphasis on smoking, protein p16INK4a expression, and HPV status. Neoplasma, 59, 398-408. https://doi.org/10.4149/neo_2012_052
  35. Larsen SR, Johansen J, Sorensen JA, et al (2009). The prognostic significance of histological features in oral squamous cell carcinoma. J Oral Pathol Med, 38, 657-62. https://doi.org/10.1111/j.1600-0714.2009.00797.x
  36. Marklund L, Hammarstedt L (2011). Impact of HPV in Oropharyngeal Cancer. J Oncol, 2011, 1-6.
  37. Minawaer, Ahmatjan A, Suzuk L (2001). [Detection of HPV type 16, 18 infection and p53 protein overexpression in oral squamous cell carcinoma]. Zhonghua Kou Qiang Yi Xue Za Zhi, 36, 451-3.
  38. Muirhead DM (2006). Correlation of clinicopathological features with immunohistochemical expression of cell cycle regulatory proteins p16 and retinoblastoma: distinct association with keratinisation and differentiation in oral cavity squamous cell carcinoma. J Clin Pathol, 59, 711-5. https://doi.org/10.1136/jcp.2005.030502
  39. Nemes JA, Deli L, Nemes Z, et al (2006). Expression of p16(INK4A), p53, and Rb proteins are independent from the presence of human papillomavirus genes in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 102, 344-52. https://doi.org/10.1016/j.tripleo.2005.10.069
  40. Padmanabhan S, Amin T, Sampat B, et al (2010). Intellectual property, technology transfer and manufacture of low-cost HPV vaccines in India. Nat Biotechnol, 28, 671-8. https://doi.org/10.1038/nbt0710-671
  41. Pande P, Mathur M, Shukla NK, et al (1998). pRb and p16 protein alterations in human oral tumorigenesis. Oral Oncol, 34, 396-403. https://doi.org/10.1016/S1368-8375(98)00024-4
  42. Pannone G, Rodolico V, Santoro A, et al (2012). 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, 7, 1-14. https://doi.org/10.1186/1750-9378-7-1
  43. Ramshankar V, Soundara VT, Shyamsundar V, et al (2014). Risk Stratification of Early Stage Oral Tongue Cancers Based on HPV Status and p16 Immunoexpression. Asian Pac J Cancer Prev, 15, 8351-9. https://doi.org/10.7314/APJCP.2014.15.19.8351
  44. Rautava J, Syrjanen S (2012). Biology of human papillomavirus infections in head and neck carcinogenesis. Head Neck Pathol, 6, 3-15. https://doi.org/10.1007/s12105-012-0367-2
  45. Robbins SL, Kumar V, Cotran RS (2010). Robbins and Cotran pathologic basis of disease, Philadelphia, PA, Saunders/Elsevier.
  46. Sanketh DS, Patil S, Rao RS, et al (2014). Analysis of human papilloma virus in oral squamous cell carcinoma using p16: An immunohistochemical study. J Int Society Prev Commun Dentist, 4, 61-6. https://doi.org/10.4103/2231-0762.131269
  47. Shaw R, Robinson M (2011). The increasing clinical relevance of human papillomavirus type 16 (HPV-16) infection in oropharyngeal cancer. British J Oral Max Surg, 49, 423-9. https://doi.org/10.1016/j.bjoms.2010.06.023
  48. Shima K, Kobayashi I, Saito I, et al (2000). Incidence of human papillomavirus 16 and 18 infection and p53 mutation in patients with oral squamous cell carcinoma in Japan. British J Oral Max Surg, 38, 445-50. https://doi.org/10.1054/bjom.2000.0162
  49. Singhi AD, Westra WH (2010). 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, 116, 2166-73.
  50. Snietura M, Jaworska M, Piglowski W, et al (2010). High-risk HPV DNA status and p16 (INK4a) expression as prognostic markers in patients with squamous cell cancer of oral cavity and oropharynx. Pol J Pathol, 61, 133-9.
  51. Stephen JK, Divine G, Chen KM, et al (2012). Significance of p16 in site-specific HPV positive and HPV negative HNSCC. Cancer Clin Oncol, 2, 51-61.
  52. Sumida T, Hamakawa H (2001). Telomerase and oral cancer. Oral Oncol, 37, 333-40. https://doi.org/10.1016/S1368-8375(00)00132-9
  53. Syrjanen S, Lodi G, von Bultzingslowen I, et al (2011). Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review. Oral Dis, 17, 58-72. https://doi.org/10.1111/j.1601-0825.2011.01792.x
  54. Tsantoulis PK, Kastrinakis NG, Tourvas AD, et al (2007). Advances in the biology of oral cancer. Oral Oncol, 43, 523-34. https://doi.org/10.1016/j.oraloncology.2006.11.010
  55. van Monsjou HS, Wreesmann VB, van den Brekel MWM, et al (2013). Head and neck squamous cell carcinoma in young patients. Oral Oncol, 49, 1097-102. https://doi.org/10.1016/j.oraloncology.2013.09.001
  56. Vargas-Ferreira F NF, Etges A, Gomes A, Furuse C, Tarquinio S (2012). Etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers: A brief approach. Brazilian Dental J, 23, 586-90. https://doi.org/10.1590/S0103-64402012000500020
  57. Vincent TL, Gatenby RA (2008). An evolutionary model for initiation, promotion, and progression in carcinogenesis. Int J Oncol, 32, 729-37.
  58. Weinberger PM, Yu Z, Haffty BG, et al (2004). Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer. Clin Cancer Res, 10, 5684-91. https://doi.org/10.1158/1078-0432.CCR-04-0448
  59. Wierzbicka M, Jozefiak A, Jackowska J, et al (2014). HPV vaccination in head and neck HPV-related pathologies. Otolaryngol Pol, 68, 157-73. https://doi.org/10.1016/j.otpol.2014.05.004
  60. Zhang ZY, Sdek P, Cao J, et al (2004). Human papillomavirus type 16 and 18 DNA in oral squamous cell carcinoma and normal mucosa. Int J Oral Max Surg, 33, 71-4. https://doi.org/10.1054/ijom.2002.0443
  61. Zhao D, Xu Qg, Chen Xm, et al (2009). Human papillomavirus as an independent predictor in oral squamous cell cancer. Int J Oral Sci, 1, 119-25. https://doi.org/10.4248/IJOS.09015
  62. Zhao S-F, Yang X-D, Lu M-X, et al (2013). Prognostic significance of VEGF immunohistochemical expression in oral cancer: a meta-analysis of the literature. Tumor Biol, 34, 3165-71. https://doi.org/10.1007/s13277-013-0886-9
  63. Zhu C DC, Ling Y, Zhou X, Wang F (2012). The relationship between oral squamous cell carcinoma and human papillomavirus: A meta-analysis of a Chinese population (1994-2011). PLoS One, 7, 1-6.

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