Oral and Maxillofacial Pathology
Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: Characterization of a distinct phenotype

https://doi.org/10.1016/j.tripleo.2005.08.001Get rights and content

We have recently shown that HPV-positive tonsillar carcinoma in young patients exhibits nonkeratinizing basaloid morphology and a characteristic immunophenotype. The purpose of this study was to review a large number of cases of oropharyngeal carcinomas, in all age groups, and to identify tumors with nonkeratinizing morphology. Using polymerase chain reaction (PCR) the prevalence and type of HPV DNA was determined in representative cases and in a control group of conventional keratinizing squamous cell carcinomas. The tumors were further characterized with a panel of immunohistochemical stains.

A total of 235 carcinomas were reviewed; 141 of the tonsils and 94 in the base of tongue. Ninety (36%) of the tonsillar and 30 (32%) of the base of tongue carcinomas were nonkeratinizing (NKCa) with basal cell features; the rest were classical keratinizing squamous cell carcinomas (KSCC). HPV DNA, particularly type 16, was identified in 10 (100%) of 10 of NKCA and in only 2 (20%) of 10 of KSCC (P = .0014). NKCas were strongly reactive to p16 antibodies while KSCC showed weak and focal reactivity. Higher Ki67 and lower p53 staining scores were observed in NKCa as compared to KSCC. It is concluded that NKCa of the tonsils and base of tongue is a distinct subtype of squamous cell carcinoma of the head and neck with high prevalence of HPV DNA and a characteristic immunophnotype.

Section snippets

Materials and methods

A total of 235 cases of squamous cell carcinoma of the tonsils and base of tongue were retrieved from the archival files of the department of pathology and immunology at Washington University School of Medicine, St Louis, Mo. Hematoxylin and eosin–stained sections were reviewed and the tumors were classified according to their histologic features into conventional KSCC (Fig. 1) and NKCa. The latter is microscopically distinct and is characterized by relatively monomorphic, ovoid, and

Results

Of the 235 cases of carcinomas studied, 141 were located in the tonsils and 51 (36%) of these were NKCa. In the base of tongue, 94 carcinomas were identified and 30 (32%) were NKCa. The ages and sex distribution of these patients are shown in Table I.

High-risk HPV DNA was identified in 12 of the 20 cases tested. HPV type 16 was found in 10 cases while types c31/33 were detected in 2 cases (Fig. 3 and Table II). All of 10 NKCa were HPV positive while HPV DNA was identified in only 2 of the 10

Discussion

In this study we have demonstrated that about one third of squamous cell carcinomas of the tonsil and base of tongue areas of Waldyer's ring of the oropharynx show a distinct phenotype. Microscopically these tumors have a nonkeratinizing morphology with basal cell features (Fig. 2). The identification of high-risk HPV DNA, predominantly type 16, in all randomly selected cases of these tumors is strongly suggestive of their viral etiology. In addition to their characteristic morphology and

References (39)

  • J. Mork et al.

    Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

    N Engl J Med

    (2001)
  • V.M. van Houten et al.

    Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas

    Int J Cancer

    (2001)
  • J.P. Klussmann et al.

    Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas

    Cancer

    (2001)
  • A. Forastiere et al.

    Head and neck cancer

    N Engl J Med

    (2001)
  • S.K. El-Mofty et al.

    Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity

    Am J Surg Pathol

    (2003)
  • P.J. Snijders et al.

    Prevalence of mucosotropic human papillomaviruses in squamous-cell carcinoma of the head and neck

    Int J Cancer

    (1996)
  • P.K. Ha et al.

    Real-time quantitative PCR demonstrates low prevalence of human papillomavirus type 16 in premalignant and malignant lesions of the oral cavity

    Clin Cancer Res

    (2002)
  • W.M. Koch et al.

    Head and neck cancer in nonsmokers: a distinct clinical and molecular entity

    Laryngoscope

    (1999)
  • M.L. Gillison et al.

    Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers

    Curr Opin Oncol

    (2001)
  • Cited by (146)

    • Head and Neck

      2021, Gattuso’s Differential Diagnosis in Surgical Pathology
    • In situ hybridization for high risk HPV E6/E7 mRNA in oropharyngeal squamous cell carcinoma

      2021, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
    • The role of tumour morphology in assigning HPV status in oropharyngeal squamous cell carcinoma

      2020, Oral Oncology
      Citation Excerpt :

      However, in one study in an Irish cohort of 226 OPSCC patients, only 31% had HPV related disease based on dual HPV DNA PCR and p16 positivity [33], while in the present study, the rate was 50%. Non-keratinizing tumour morphology including in cervical lymph node metastases has previously been shown to correlate highly with p16 positivity, HPV positivity [13,14,34,35] and survival outcomes [35]. Prior 2012 CAP guidelines recognized that tumour morphology (keratinizing versus non-keratinizing) in combination with p16 status is a better predictor of HPV status than p16 IHC alone.

    View all citing articles on Scopus
    View full text