Tumor Biology

, Volume 34, Issue 1, pp 301–307

Human papillomavirus infection and papillary squamous cell carcinoma in the head and neck region

Research Article


Papillary squamous cell carcinoma (PSCC) is a rare variant of SCC in the head and neck region. The role of human papillomavirus (HPV) infection in PSCC is still unclear. We retrospectively reviewed 11 PSCCs in our institute over a 21-year period and compared the HPV status of PSCCs with 26 squamous cell papillomas (SCPs). Polymerase chain reaction (PCR) amplification to detect HPV DNA and in situ hybridization (ISH) were performed to analyze the relationship between the papillary lesions and HPV infection. Immunohistochemical (IHC) staining for p16 protein expression was used to analyze the PSCC specimens. Nine of 11 (82 %), eight of 11 (73 %), and eight of 11 (73 %) PSCC samples were found to be HPV positive by PCR, ISH, and IHC staining for p16 protein expression, respectively. PSCC had a significantly higher rate of HPV infection than SCP by PCR (p = 0.002) and ISH (p = 0.001) analysis. This study presents different HPV status in two papillary neoplasms and may help to clarify the unique morphological and biological characteristics of head and neck PSCC.


Papillary squamous cell carcinoma Squamous cell papilloma Human papillomavirus p16 HNSCC 


  1. 1.
    Crissman JD, Kessis T, Shah KV, Fu YS, Stoler MH, Zarbo RJ, et al. Squamous papillary neoplasia of the adult upper aerodigestive tract. Hum Pathol. 1988;19:1387–96.PubMedCrossRefGoogle Scholar
  2. 2.
    Ishiyama A, Eversole LR, Ross DA, Raz Y, Kerner MM, Fu YS, et al. Papillary squamous neoplasms of the head and neck. Laryngoscope. 1994;104:1446–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Colby C, Klein AM. Papillary squamous cell carcinoma of the larynx. Ear Nose Throat J. 2011;90:E13–5.PubMedGoogle Scholar
  4. 4.
    Ferlito A, Devaney KO, Rinaldo A, Putzi MJ. Papillary squamous cell carcinoma versus verrucous squamous cell carcinoma of the head and neck. Ann Otol Rhinol Laryngol. 1999;108:318–22.PubMedGoogle Scholar
  5. 5.
    Cobo F, Talavera P, Concha A. Review article: relationship of human papillomavirus with papillary squamous cell carcinoma of the upper aerodigestive tract: a review. Int J Surg Pathol. 2008;16:127–36.PubMedCrossRefGoogle Scholar
  6. 6.
    Hwang CF, Huang CC, Chien CY, Huang SC, Yang CH, Su CY. Human papillomavirus infection in oral papillary and verrucous lesions is a prognostic indicator of malignant transformation. Cancer Epidemiol. 2012;36:e122–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Al-Swiahb JN, Huang CC, Fang FM, Chuang HC, Huang HY, Luo SD, et al. Prognostic impact of p16, p53, epidermal growth factor receptor, and human papillomavirus in oropharyngeal cancer in a betel nut-chewing area. Arch Otolaryngol Head Neck Surg. 2010;136:502–8.PubMedCrossRefGoogle Scholar
  8. 8.
    O'Regan EM, Toner ME, Finn SP, Fan CY, Ring M, Hagmar B, et al. P16(ink4a) genetic and epigenetic profiles differ in relation to age and site in head and neck squamous cell carcinomas. Hum Pathol. 2008;39:452–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Mirhashemi R, Ganjei-Azar P, Nadji M, Lambrou N, Atamdede F, Averette HE. Papillary squamous cell carcinoma of the uterine cervix: an immunophenotypic appraisal of 12 cases. Gynecol Oncol. 2003;90:657–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Suarez PA, Adler-Storthz K, Luna MA, El-Naggar AK, Abdul-Karim FW, Batsakis JG. Papillary squamous cell carcinomas of the upper aerodigestive tract: a clinicopathologic and molecular study. Head Neck. 2000;22:360–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Thompson LD, Wenig BM, Heffner DK, Gnepp DR. Exophytic and papillary squamous cell carcinomas of the larynx: a clinicopathologic series of 104 cases. Otolaryngol Head Neck Surg. 1999;120:718–24.PubMedCrossRefGoogle Scholar
  12. 12.
    Jo VY, Mills SE, Stoler MH, Stelow EB. Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma. Am J Surg Pathol. 2009;33:1720–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Klussmann JP, Weissenborn SJ, Wieland U, Dries V, Kolligs J, Jungehuelsing M, et al. Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer. 2001;92:2875–84.PubMedCrossRefGoogle Scholar
  14. 14.
    Venuti A, Badaracco G, Rizzo C, Mafera B, Rahimi S, Vigili M. Presence of HPV in head and neck tumours: high prevalence in tonsillar localization. J Exp Clin Cancer Res. 2004;23:561–6.PubMedGoogle Scholar
  15. 15.
    Paz IB, Cook N, Odom-Maryon T, Xie Y, Wilczynski SP. Human papillomavirus (HPV) in head and neck cancer. An association of HPV 16 with squamous cell carcinoma of Waldeyer's tonsillar ring. Cancer. 1997;79:595–604.PubMedCrossRefGoogle Scholar
  16. 16.
    Cobo F, Garcia C, Talavera P, Bravo J, Cabrera C, Concha A. Human papillomavirus associated with papillary squamous cell carcinoma of the oropharynx in a renal transplant recipient. Infection. 2006;34:176–80.PubMedCrossRefGoogle Scholar
  17. 17.
    Reed AL, Califano J, Cairns P, Westra WH, Jones RM, Koch W, et al. High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res. 1996;56:3630–3.PubMedGoogle Scholar
  18. 18.
    Rawnsley JD, Srivatsan ES, Chakrabarti R, Billings KR, Wang MB. Deletion analysis of the p16/CDKN2 gene in head and neck squamous cell carcinoma using quantitative polymerase chain reaction method. Arch Otolaryngol Head Neck Surg. 1997;123:863–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Ai L, Stephenson KK, Ling W, Zuo C, Mukunyadzi P, Suen JY, et al. The p16 (CDKN2A/INK4A) tumor-suppressor gene in head and neck squamous cell carcinoma: a promoter methylation and protein expression study in 100 cases. Mod Pathol. 2003;16:944–50.PubMedCrossRefGoogle Scholar
  20. 20.
    Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T. Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions. Am J Pathol. 1998;153:1741–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Klussmann JP, Gultekin E, Weissenborn SJ, Wieland U, Dries V, Dienes HP, et al. Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol. 2003;162:747–53.PubMedCrossRefGoogle Scholar
  22. 22.
    Li W, Thompson CH, Cossart YE, O'Brien CJ, McNeil EB, Scolyer RA, et al. The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil. Head Neck. 2004;26:1–9.PubMedCrossRefGoogle Scholar
  23. 23.
    El-Naggar AK, Lai S, Clayman GL, Zhou JH, Tucker SA, Myers J, et al. Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications. Hum Pathol. 1999;30:1013–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Pande P, Mathur M, Shukla NK, Ralhan R. Prb and p16 protein alterations in human oral tumorigenesis. Oral Oncol. 1998;34:396–403.PubMedCrossRefGoogle Scholar
  25. 25.
    Higuchi E, Oridate N, Homma A, Suzuki F, Atago Y, Nagahashi T, et al. Prognostic significance of cyclin D1 and p16 in patients with intermediate-risk head and neck squamous cell carcinoma treated with docetaxel and concurrent radiotherapy. Head Neck. 2007;29:940–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Chien CY, Su CY, Fang FM, Huang HY, Chuang HC, Chen CM, et al. Lower prevalence but favorable survival for human papillomavirus-related squamous cell carcinoma of tonsil in taiwan. Oral Oncol. 2008;44:174–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Campbell AC, Gleich LL, Barrett WL, Gluckman JL. Cancerous seeding of the tracheotomy site in patients with upper aerodigestive tract squamous cell carcinoma. Otolaryngol Head Neck Surg. 1999;120:601–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001;344:1125–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Smith EM, Hoffman HT, Summersgill KS, Kirchner HL, Turek LP, Haugen TH. Human papillomavirus and risk of oral cancer. Laryngoscope. 1998;108:1098–103.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  1. 1.Department of OtolaryngologyKaohsiung Chang Gung Memorial HospitalKaohsiungRepublic of China
  2. 2.Graduate Institute of Clinical Medical SciencesChang Gung University College of MedicineKaohsiungRepublic of China
  3. 3.Department of PathologyKaohsiung Chang Gung Memorial HospitalKaohsiungRepublic of China
  4. 4.Chang Gung University College of MedicineKaohsiung CityRepublic of China

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