HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer

  • Jan Klozar
  • Vit Kratochvil
  • Martina Salakova
  • Jana Smahelova
  • Eva Vesela
  • Eva Hamsikova
  • Jan Betka
  • Ruth TachezyEmail author
Head and Neck


Prognostic factors are important for treatment decisions as they help adapt the therapy on a case-to-case basis. Nodal status, number of positive nodes, and presence of extracapsular spread are considered to be the important prognostic factors in head and neck cancer. Some studies suggest that human papillomavirus (HPV) status also influences the outcome of the treatment. This influence can be explained by the variation in tendency to develop regional metastases and by variation in the type of neck node involvement. The study objectives were to compare patients with HPV positive and HPV-negative tumors for survival and prevalence and type of regional metastasis, to identify prognostic factors and to test whether HPV presence is an independent factor of survival. The study included 81 patients treated by surgery including neck dissection for oral or oropharyngeal squamous cell cancer. A computerized medical report was completed for each patient. Analysis of the tumor specimen for the HPV DNA presence was done on paraffin-fixed tissue. HPV DNA detection and typing were performed by PCR with GP5 + /GP6 + BIO primers and reverse line blot hybridization. Overall, 64% (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive patients had significantly better both overall (73 vs. 35%) (P = 0.0112) and disease-specific (79 vs. 45%) (P = 0.0015) survival rates than HPV-negative patients. No significant differences were found in the pN classification, in the number of positive nodes and the presence of extracapsular spread in the involved nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed that significant prognostic factors of survival were the presence of HPV in the tumor, extracapsular spread and tumor size. HPV was the most significant prognostic factor in the studied group of patients with oropharyngeal tumors (HR = 0.27, 95%CI 0.12–0.61) and possibly should be considered in treatment decisions.


Oropharyngeal cancer Oral cancer HPV Lymph nodes Survival Prognostic factors 



The authors thank Zdenek Roth for statistical evaluation of data and editing the manuscript. The study was supported by grant NR 8126-3 of the Internal Grant Agency of the Czech Ministry of Health.

Conflict of interest statement

The authors declare that they have no conflict of interest.


  1. 1.
    Cancer Incidence 2003. UZIS, Prague (2006)Google Scholar
  2. 2.
    Andl T, Kahn T, Pfuhl A, Nicola T, Erber R, Conradt C, Klein W, Helbig M, Dietz A, Weidauer H, Bosch FX (1998) Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res 58:5–13PubMedGoogle Scholar
  3. 3.
    Dahlgren L, Dahlstrand HM, Lindquist D, Hogmo A, Bjornestal L, Lindholm J, Lundberg B, Dalianis T, Munck-Wikland E (2004) Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients. Int J Cancer 112:1015–1019PubMedCrossRefGoogle Scholar
  4. 4.
    Dahlstrand HM, Dalianis T (2005) Presence and influence of human papillomaviruses (HPV) in Tonsillar cancer. Adv Cancer Res 93:59–89PubMedCrossRefGoogle Scholar
  5. 5.
    Dahlstrom KR, Adler-Storthz K, Etzel CJ, Liu Z, Dillon L, El-Naggar AK, Spitz MR, Schiller JT, Wei Q, Sturgis EM (2003) Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. Clin Cancer Res 9:2620–2626PubMedGoogle Scholar
  6. 6.
    Gillison ML (2007) Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head Neck 29(8):779–792PubMedCrossRefGoogle Scholar
  7. 7.
    Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720PubMedCrossRefGoogle Scholar
  8. 8.
    Greenberg JS, Fowler R, Gomez J, Mo V, Roberts D, El Naggar AK, Myers JN (2003) Extent of extracapsular spread: a critical prognosticator in oral tongue cancer. Cancer 97:1464–1470PubMedCrossRefGoogle Scholar
  9. 9.
    Hobbs CG, Sterne JA, Bailey M, Heyderman RS, Birchall MA, Thomas SJ (2006) Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol 31:259–266PubMedCrossRefGoogle Scholar
  10. 10.
    Hoffmann M, Gorogh T, Gottschlich S, Lohrey C, Rittgen W, Ambrosch P, Schwarz E, Kahn T (2005) Human papillomaviruses in head and neck cancer: 8 year-survival-analysis of 73 patients. Cancer Lett 218:199–206PubMedCrossRefGoogle Scholar
  11. 11.
    Klussmann JP, Weissenborn SJ, Wieland U, Dries V, Eckel HE, Pfister HJ, Fuchs PG (2003) Human papillomavirus-positive tonsillar carcinomas: a different tumor entity? Med Microbiol Immunol (Berl) 192:129–132CrossRefGoogle Scholar
  12. 12.
    Koskinen WJ, Chen RW, Leivo I, Makitie A, Back L, Kontio R, Suuronen R, Lindqvist C, Auvinen E, Molijn A, Quint WG, Vaheri A, Aaltonen LM (2003) Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck. Int J Cancer 107:401–406PubMedCrossRefGoogle Scholar
  13. 13.
    Kreimer AR, Clifford GM, Boyle P, Franceschi S (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14:467–475PubMedCrossRefGoogle Scholar
  14. 14.
    Li W, Thompson CH, O’Brien CJ, McNeil EB, Scolyer RA, Cossart YE, Veness MJ, Walker DM, Morgan GJ, Rose BR (2003) Human papillomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil. Int J Cancer 106:553–558PubMedCrossRefGoogle Scholar
  15. 15.
    Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM (2001) Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 92:805–813PubMedCrossRefGoogle Scholar
  16. 16.
    Mellin H, Friesland S, Lewensohn R, Dalianis T, Munck-Wikland E (2000) Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer 89:300–304PubMedCrossRefGoogle Scholar
  17. 17.
    Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, Moller B, Pukkala E, Schiller JT, Youngman L, Lehtinen M, Dillner J (2001) Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344:1125–1131PubMedCrossRefGoogle Scholar
  18. 18.
    Ritchie JM, Smith EM, Summersgill KF, Hoffman HT, Wang D, Klussmann JP, Turek LP, Haugen TH (2003) Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer 104:336–344PubMedCrossRefGoogle Scholar
  19. 19.
    Shah J (2003) Head and neck surgery and oncology. Mosby, EdinburghGoogle Scholar
  20. 20.
    Schlecht NF (2005) Prognostic value of human papillomavirus in the survival of head and neck cancer patients: an overview of the evidence. Oncol Rep 14:1239–1247PubMedGoogle Scholar
  21. 21.
    Schwartz SR, Yueh B, McDougall JK, Daling JR, Schwartz SM (2001) Human papillomavirus infection and survival in oral squamous cell cancer: a population-based study. Otolaryngol Head Neck Surg 125:1–9PubMedCrossRefGoogle Scholar
  22. 22.
    Smith EM, Ritchie JM, Summersgill KF, Klussmann JP, Lee JH, Wang D, Haugen TH, Turek LP (2004) Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer 108:766–772PubMedCrossRefGoogle Scholar
  23. 23.
    Strome SE, Savva A, Brissett AE, Gostout BS, Lewis J, Clayton AC, McGovern R, Weaver AL, Persing D, Kasperbauer JL (2002) Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations. Clin Cancer Res 8:1093–1100PubMedGoogle Scholar
  24. 24.
    Tachezy R, Klozar J, Salakova M, Smith E, Turek L, Betka J, Kodet R, Hamsikova E (2005) HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic. Oral Dis 11:181–185PubMedCrossRefGoogle Scholar
  25. 25.
    van den Brule AJ, Pol R, Fransen-Daalmeijer N, Schouls LM, Meijer CJ, Snijders PJ (2002) GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol 40:779–787PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jan Klozar
    • 1
  • Vit Kratochvil
    • 1
  • Martina Salakova
    • 2
  • Jana Smahelova
    • 2
  • Eva Vesela
    • 3
  • Eva Hamsikova
    • 2
  • Jan Betka
    • 1
  • Ruth Tachezy
    • 2
    Email author
  1. 1.Department of Otolaryngology Head and Neck Surgery, 1st Faculty of MedicineCharles UniversityPragueCzech Republic
  2. 2.Department of Experimental Virology, Institute of Hematology and Blood TransfusionNational Reference Laboratory for PapillomavirusesPrague 2Czech Republic
  3. 3.Department of Pathology and Molecular Biology, 2nd Faculty of MedicineCharles UniversityPragueCzech Republic

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