Skip to main content

Advertisement

SpringerLink
Log in

An Analysis of the Epidemiological and Etiological Factors of Oral Tumors of Young Adults in a Central-Eastern European Population

  • Review
  • Published:
Pathology & Oncology Research

Abstract

The etiology of tumors in young age is not precisely known yet, but studies on the topic generally agree that in this group of patients the traditionally known behavioural risk factors (tobacco and alcohol abuse) play no or a significantly less important role. Oral squamous cell carcinoma occurring at a young age is a topic of utmost importance that is extensively and intensively researched as, while the overall incidence of oral cancer is decreasing worldwide, that of squamous cell carcinoma diagnosed in young adults is steadily increasing. The present article aims at presenting the main questions and characteristics of tumors in young adults in Central-Eastern Europe and in developed West European countries as contrasted to tumors found in middle aged and elderly patients. Factors influencing the development of oral cancer include regulatory factors of the cell cycle, the inherited vulnerability of the genetic code of certain proteins and the presence of HPV infection with an oncogenic genotype. The connections of HPV infection and genetic damages are studied intensively. It is known that the prevalence of oral HPV infections is growing with a background of potentially changing sexual habits. It is debated, however, whether smoking and alcohol consumption could have a connection to HPV associated oral cancer and whether the spread of HPV in itself could be an explanation for the growing occurrence of young-age tumors. There is no consensus in the literature as to the prognostic significance of age. Some research groups have found a better life expectancy for young patients, while other authors found a worse prognosis for these patients. It is known that the prognosis of head and neck tumors, the prevalence of HPV infections as well as genetic mutations show regional and ethnic variations. This might be explained by differences in the degree of development of a preventive system, in the quality of care and in the attitudes of young patients towards visiting a doctor. The study is made difficult by incomparable patient selection criteria as well as by the question of the intraoral localisation of tumors as an independent risk factor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

Akt:

Protein kinase B, serine/threonine protein kinase

Bcl-2:

B cell lymphoma 2

CCND1:

Cyclin D1 coding gene

DHAS:

Dehydroepiandrosterone-sulphate

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

FSH:

Follicle stimulating hormone

hMSH2:

MutS homolog 2

hMLH1:

MutL homolog 1

HPV:

Human papilloma virus

IRF6:

Interferon regulating factor 6

LH:

Luteinizing hormone

LI:

Leukocyte-interleukin

MAPK:

Mitogen activated protein kinase

MTHFR:

Methylene tetrahydrofolate reductase

NF-κB:

Nuclear factor-kappa B

PCNA:

Proactive cell nuclear antigen

PIK3CA:

Phosphatidylinositol −4,5-bisphosphate 3 kinase catalytic subunit alpha

PR:

Progesterone receptor

PRL:

Prolactin

PTEN:

Phosphatase and tensin homolog

TE:

Testosterone

XRCC1:

DNA repair protein= X-ray repair cross-complementing protein 1

5-FU:

5-fluorouracil

References

  1. Chen JK, Eisenberg E et al (1991) Changing trends in oral cancers in the United States, 1935 to 1985: a Connecticut study. J Oral Maxillofac Surg 49:1152–1158

    Article  PubMed  CAS  Google Scholar 

  2. Annertz K, Anderson H et al (2002) Incidence and survival of squamous cell carcinoma of the tongue in Scandinavia, with special reference to young adults. Int J Cancer 101:95–99

    Article  PubMed  CAS  Google Scholar 

  3. Llewellyn CD, Johnson NW, Warnakulasuriya KA (2004) Risk factors for oral cancer in newly diagnosed patients aged 45 years and younger: a case–control study in Southern England. J Oral Pathol Med 33:525–532

    Article  PubMed  CAS  Google Scholar 

  4. BDA (2000) Opportunistic oral cancer screening. British Dental Association Occasional Paper No 6, London

  5. Schantz SP, Yu GP (2002) Head and neck cancer incidence trends in young Americans, 1973–1997, with a special analysis for tongue cancer. Arch Otolaryngol Head Neck Surg 128:268–274

    Article  PubMed  Google Scholar 

  6. National Cancer Registry, http://www.honcology.hu/portal/page/portal/OOI/MEDICAL_ATTENDANCE/medical_departments/MD_901

  7. Müller S, Pan Y et al (2008) Changing trends in oral squamous cell carcinoma with particular reference to young patients:1971–2006. The Emory university experience. Head Neck Pathol 2:60–66

    Article  PubMed  Google Scholar 

  8. Siriwardena BS, Tilakaratne A et al (2006) Demographic, aetiological and survival differences of oral squamous cell carcinoma in the young and the old in Sri Lanka. Oral Oncol 42:831–836

    Article  PubMed  CAS  Google Scholar 

  9. Brown LM, Check DP, Devesa SS (2012) Oral cavity and pharynx cancer incidence trends by subsite in the United States: changing gender patterns. J Oncol 2012:649498. doi:10.1155/2012/649498

    PubMed  Google Scholar 

  10. Horn C, Thaker HM, Tampakopoulou DA et al (2001) Tongue lesions in the pediatric population. Otolaryngol Head Neck Surg 124:164–169

    Article  PubMed  CAS  Google Scholar 

  11. Siegelmann-Danieli N, Hanlon A, Ridge JA et al (1998) Oral tongue cancer in patients less than 45 years old: institutional experience and comparison with older patients. J Clin Oncol 16:745–753

    PubMed  CAS  Google Scholar 

  12. Llewellyn CD, Johnson NW, Warnakulasurya KA (2001) Risk factors for squamosus cell carcinoma of the oral cavity in young people-a comprehensive literature review. Oral Oncol 37:401–418

    Article  PubMed  CAS  Google Scholar 

  13. http://ec.europa.eu/public_opinion/archives/ebs/ebs_332_en.pdf

  14. http://ec.europa.eu/health/tobacco/products/index_en.htm

  15. Hashibe M, Brennan P, Chuang SC et al (2009) Interaction between alcohol and tobacco use and the risk of head and neck cancer: pooled analysis in the international head and neck cancer epidemiology consortium. Cancer Epidemiol Biomarkers Prev 18:541–550

    Article  PubMed  CAS  Google Scholar 

  16. Llewellyn CD, Linklater K, Bell J et al (2004) An analysis of risk factors for oral cancer in young people: a case–control study. Oral Oncol 40:304–313

    Article  PubMed  Google Scholar 

  17. Bachar G, Hod R, Goldstein DP, Irish JC et al (2011) Outcome of oral tongue squamosus cell carcinoma in patients with or without the known risk factors. Oral Oncol 47:45–50

    Article  PubMed  CAS  Google Scholar 

  18. Rothenberg SM, Ellisen LW (2012) The molecular pathogenesis of head and neck squamous cell carcinoma. J Clin Invest 122:1951–1957

    Article  PubMed  CAS  Google Scholar 

  19. Popvic B, Jekic B, Novakovic I et al (2010) Cancer gene alterations and HPV infection in oral squamosus cell carcinoma. Int J Oral Maxillofac Surg 39:909–915

    Article  Google Scholar 

  20. Paterson IC, Eveson JW, Prime SS (1996) Molecular changes in oral cancer may reflect aetiology and ethnic origin. Eur J Cancer B Oral Oncol 32:150–153

    Article  Google Scholar 

  21. Sheikh Ali MA, Gunduz M, Nagatsuka H et al (2008) Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma. Cancer Sci 99:1589–1594

    Article  PubMed  Google Scholar 

  22. Szabó B, Nelhűbel AG, Kárpáti A et al (2011) Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas. Oral Oncol 47:487–496

    Article  PubMed  Google Scholar 

  23. Hama T, Yuza Y, Saito Y et al (2009) Prognostic significance of epidermal growth factor receptor phosphorylation and mutation in head and neck squamous cell carcinoma. Oncologist 14:900–908

    Article  PubMed  CAS  Google Scholar 

  24. Licitra L, Mesia R, Rivera F et al (2011) Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol 22:1078–1087

    Article  PubMed  CAS  Google Scholar 

  25. Smilek P, Neuwirthova J, Jarkovsky J et al (2012) Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas. Neoplasma 59:508–515

    Article  PubMed  CAS  Google Scholar 

  26. Tímár J, Csuka O, Remenár É et al (2005) Progression of head and neck squamous cell cancer. Cancer Metastasis Rev 24:107–127

    Article  PubMed  Google Scholar 

  27. Csuka O, Remenár E, Koronczay K et al (1997) Predictive value of p53, Bcl2 and bax in the radiotherapy of head and neck cancer. Pathol Oncol Res 3:204–210

    Article  PubMed  CAS  Google Scholar 

  28. Aswini YB (2009) The genomics of oral cancer and wound healing. J Indian Soc Pedod Prevent Dent 27:2–5

    Article  CAS  Google Scholar 

  29. Alvasiri NS, Mehdi MJ, Alam MS et al (2012) PTEN-mediated Akt activation contributes to the reduced apoptosis among Indian oral squamosus carcinoma patients. J Cancer Res Clin Oncol 138:103–109

    Article  Google Scholar 

  30. Lu Y, Lin YZ, Lapushin R et al (1999) The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and inoikis in breast cancer cells. Oncogene 18:7034–7045

    Article  PubMed  CAS  Google Scholar 

  31. Weng LP, Brown JL, Eng C (2001) PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways. Hum Mol Genet 10:237–242

    Article  PubMed  CAS  Google Scholar 

  32. Wang Z, Sturgis EM, Zhang Y et al (2011) Combined p53-related genetic variant together with HPV infection increase oral cancer risk. Int J Cancer 131:251–258

    Article  Google Scholar 

  33. O’Regan EM, Toner ME, Finn SP et al (2008) p16(INK4A) Genetic and epigenetic profiles differ in relation to age and site in head and neck squamosus cell carcinomas. Hum Pathol 39:452–458

    Article  PubMed  Google Scholar 

  34. Harris SL, Thorne LB, Seaman WT et al (2011) Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue. Head Neck 33:1622–1627

    Article  PubMed  Google Scholar 

  35. Zhang ZJ, Hao K, Shi R et al (2011) Glutathione S-tranferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polimorphisms, smoking, and their interaction in oral cancer: a huge review and meta-analysis. Am J Epidemiol 173:847–857

    Article  PubMed  Google Scholar 

  36. Gawecki W, Kostrzewska-Poczekai M, Gajecka M et al (2007) The role of genetic factor in etiopathogenesis of squamosus cell carcinoma of the head and neck in young adults. Eur Arch Otorhinolaryngol 12:1459–1465

    Article  Google Scholar 

  37. Toner M, O’Regan EM (2009) Head and neck squamosus cell carcinoma in the young: a spectrum or a distinct group? part 2. Head Neck Pathol 3:249–251

    Article  PubMed  CAS  Google Scholar 

  38. Lukits J, Remenár É, Rásó E et al (2007) Molecular identification, expression and prognostic role of estrogen- and progesterone receptors in head and neck cancer. Int J Oncol 30:155–160

    PubMed  CAS  Google Scholar 

  39. Remenár E, Számel I, Budai B et al (2007) Increase of hypophyseal hormone levels in male head and neck cancer patients. Pathol Oncol Res 13:341

    Article  PubMed  Google Scholar 

  40. Tímár J, Forster-Horváth C, Lukits J et al (2003) The effect of leukocyte interleukin injection (multikine®) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia:a possible New approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer-a multicenter phase I/II clinical trial. Laryngoscope 113:2206–2217

    Article  PubMed  Google Scholar 

  41. Stransky N, Egloff AM, Tward AD et al (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333:1157–1160

    Article  PubMed  CAS  Google Scholar 

  42. Kumaraswamy KL, Vidhya M (2011) Human papilloma virus and oral infections: an update. J Cancer Res Ther 7:120–127

    Article  PubMed  CAS  Google Scholar 

  43. Smith EM, Hoffman HT, Summersgill KS et al (1998) Human papilloma virus and risk of oral cancer. Laryngoscope 108:1098–1103

    Article  PubMed  CAS  Google Scholar 

  44. Gillison ML, Broutian T et al (2012) Prevalence of oral HPV infection in the United States, 2009–2010. JAMA 307:693–703. doi:10.1001/jama.2012.101

    Article  PubMed  CAS  Google Scholar 

  45. D’Souza G, Kreimer AR, Viscidi R et al (2007) Case-controll study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356:1944–1956

    Article  PubMed  Google Scholar 

  46. Cleveland JL, Junger ML et al (2011) The connection between human papillomavirus and oropharyngeal squamosus cell carcinomas in the United States: implications for dentistry. J Am Dent Assoc 142:915–924

    PubMed  Google Scholar 

  47. Syrjänen S (2010) The role of human papilloma virus infection in head and neck cancers. Ann Oncol 21:243–245

    Article  Google Scholar 

  48. Rombaldi RL, Serafini EP et al (2009) Perinatal transmission of human papillomavirus DNA. Virol J 6:83–95

    Article  PubMed  Google Scholar 

  49. Rombaldi RL, Serafini EP et al (2008) Transplacental transmission of human papillomavirus. Virol J 5:106–120

    Article  PubMed  Google Scholar 

  50. Kreimer AR, Glifford GM, Boyle P et al (2005) Human papillomavirus types in head and neck squamosus carcinomas worldwide: a systematic review. Cancer Epidemiol Biomark Prev 14:467–475

    Article  CAS  Google Scholar 

  51. Cerovac C, Sarcevic B, Kralj Z et al (1996) Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and neck squamosus cell carcinomas by in situ hybridization. Neoplasma 43:185–194

    PubMed  CAS  Google Scholar 

  52. Klozar J, Kratochvil V, Salakova M (2008) HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer. Eur Arch Otolaryngol 265:75–82

    Article  Google Scholar 

  53. Kansky AA, Poljak M, Seme K et al (2003) Human papillomavirus DNA in oral squamosus cell carcinomas and normal oral mucosa. Acta Virol 47:11–16

    PubMed  CAS  Google Scholar 

  54. Kansky AA, Seme K, Maver PJ et al (2006) Human papillomaviruses (HPV) in tissue specimens of oral squamosus cell papillomas and normal oral mucosa. Anticancer Res 26:3197–3202

    PubMed  Google Scholar 

  55. Szentirmay Z, Pólus Z, Tamás L et al (2005) Human papillomavirus in head and neck cancer: molecular biology and clinicopathological correlations. Cancer Metastasis Rev 24:19–34

    Article  PubMed  CAS  Google Scholar 

  56. Joo JH, Jung CK et al (2010) High-risk human papillomavirus and cervical lymph node metastasis in patient with oropharyngeal cancer. Head Neck 34:10–14

    Article  Google Scholar 

  57. Lill C, Kornek G et al (2011) Survival of patients with HPV-positive oropharyngeal cancer after radiochemotherapy is significantly enhanced. Wien Klin Wochenschr 123:215–221

    Article  PubMed  Google Scholar 

  58. Kozomara RJ, Brankovic-Magic MV, Jovic NR et al (2007) Prognostic significance of TP53 mutations in oral squamous cell carcinoma with human papilloma virus infection. Int J Biol Markers 22:252–257

    PubMed  CAS  Google Scholar 

  59. Hong AM, Dobbins TA et al (2010) Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer 103:1510–1517

    Article  PubMed  CAS  Google Scholar 

  60. Na II, Kang HJ, Cho SY et al (2007) EGFR mutations and human papillomavirus in squamous cell carcinoma of tongue and tonsil. Eur J Cancer 43:520–526

    Article  PubMed  CAS  Google Scholar 

  61. Byers RM (1975) Squamous cell carcinoma of the oral tongue in patients less than thirty years of age. Am J Surg 130:475–478

    Article  PubMed  CAS  Google Scholar 

  62. Garavello W, Spreafico R et al (2007) Oral tongue cancer in young patients: a matched analysis. Oral Oncol 43:894–897

    Article  PubMed  Google Scholar 

  63. Hagemann M, Zbaeren P (2002/2003) Squamous Cell Carcinoma of the Tongue in Young. Oto-Rhino-Laryngol Nova 12:295–299

  64. Sarkaria JN, Harari PM (1994) Oral tongue cancer in young adults less than 40 years of age: rational for agressive therapy. Head Neck 16:107–111

    Article  PubMed  CAS  Google Scholar 

  65. Mallet Y, Avalaos N et al (2009) Head and neck cancer in young people: a series of 52 SCCs of the oral tongue in patients aged 35 years or less. Acta Otolaryngol 129:1503–1508

    Article  PubMed  Google Scholar 

  66. Gawecki W, Szyfter K, Szyfter W et al (2007) Clinical and histopatological analysis of squamosus cell carcinoma of the head and neck in young adults. Otolaryngol Pol 61:11–16

    Article  PubMed  Google Scholar 

  67. Pytinia KB, Grant JR, Etzel CJ et al (2004) Matched analysis of survival in patients with squamosus cell carcinoma of the head and neck diagnosed before and after 40 years of age. Arch Otolanryngol Head Neck Surg 130:869–873

    Article  Google Scholar 

  68. Falaki F, Dalirsani Z, Pakfetrat A et al (2011) Clinical and hystopatological analysis of oral squamosus cell carcinoma of young patients in Mashad, Iran: A retrospective study and review of literatures. Med Oral Patol Oral Cir Bucal 16:473–477

    Article  Google Scholar 

  69. Zigon G, Berrino F, Gatta G et al (2011) Prognosis for head and neck cancers in Europe diagnosed in 1995–1999: a population-based study. Ann Oncol 22:165–174

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oro-Maxillofacial Surgery and Stomatology, Faculty of Dentistry, Semmelweis University, Budapest, Mária str. 52, 1085, Budapest, Hungary

    K. Túri, P. Barabás, K. Csurgay, Gy. Léhner, Á. Lőrincz & Zs. Németh

Authors
  1. K. Túri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Barabás
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Csurgay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gy. Léhner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Á. Lőrincz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zs. Németh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zs. Németh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Túri, K., Barabás, P., Csurgay, K. et al. An Analysis of the Epidemiological and Etiological Factors of Oral Tumors of Young Adults in a Central-Eastern European Population. Pathol. Oncol. Res. 19, 353–363 (2013). https://doi.org/10.1007/s12253-013-9628-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-013-9628-y

Keywords

Search

Navigation