Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma

Shahnaz Begum, Dengfeng Cao, Maura Gillison, Marianna Zahurak, William H. Westra

Research output: Contribution to journalArticle

Abstract

Purpose: Human papillomavirus 16 (HPV-16) has been implicated as a causative agent in a subset of head and neck squamous cell carcinomas (HNSCC). This study was undertaken to discern the distribution and timing of HPV viral integration during tumorigenesis of the upper respiratory tract. Experimental Design: A tissue array was assembled from a consecutive group of 176 patients with HNSCCs. The array was evaluated by HPV-16 in situ hybridization and p16 immunohistochemistry. Patients with HPV-positive tonsillar cancers who had undergone bilateral tonsillectomies were selected for more complete mapping of viral integration. Results: HPV-16 was detected in 38 of the 176 (22%) cases by in situ hybridization. When stratified by site of origin, HPV-16 was detected in 37 of 45 cancers arising from the oropharynx but in only 1 of 131 tumors arising from nonoropharyngeal sites (82% versus 0.8%, P <0.00001). P16 expression was associated with the presence of HPV-16: 31 of 38 HPV-positive tumors exhibited p16 expression, whereas only 9 of the 138 HPV-negative tumors were p16-positive (82% versus 6%, P <0.00001). In the bilateral tonsil sections, hybridization signals were strictly limited to the invasive cancers and associated dysplasias. P16 staining was widely distributed throughout the nonneoplastic crypt epithelium of individuals with and without tonsillar cancer. Conclusions: HPV-16 is strongly associated with carcinomas arising from the oropharynx, and integration is tightly coupled to the neoplastic process. Viral integration does not occur as a field alteration throughout normal tonsillar epithelium. P16 expression localizes to HPV-positive cancers, and is intrinsic to the specialized epithelium of the tonsillar crypts. For risk assessment, early cancer detection and disease surveillance, evidence of HPV-16 integration may represent a meaningful finding, whereas high p16 expression, by itself, may not.

Original languageEnglish (US)
Pages (from-to)5694-5699
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number16
DOIs
StatePublished - Aug 15 2005

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Human papillomavirus 16
Tissue Distribution
Carcinoma
Virus Integration
DNA
Tonsillar Neoplasms
Neoplasms
Epithelium
In Situ Hybridization
Human papillomavirus 31
Oropharyngeal Neoplasms
Neoplastic Processes
Oropharynx
Tonsillectomy
Palatine Tonsil
Respiratory System
Early Diagnosis
Carcinogenesis
Research Design
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma. / Begum, Shahnaz; Cao, Dengfeng; Gillison, Maura; Zahurak, Marianna; Westra, William H.

In: Clinical Cancer Research, Vol. 11, No. 16, 15.08.2005, p. 5694-5699.

Research output: Contribution to journalArticle

Begum, Shahnaz ; Cao, Dengfeng ; Gillison, Maura ; Zahurak, Marianna ; Westra, William H. / Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 16. pp. 5694-5699.
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abstract = "Purpose: Human papillomavirus 16 (HPV-16) has been implicated as a causative agent in a subset of head and neck squamous cell carcinomas (HNSCC). This study was undertaken to discern the distribution and timing of HPV viral integration during tumorigenesis of the upper respiratory tract. Experimental Design: A tissue array was assembled from a consecutive group of 176 patients with HNSCCs. The array was evaluated by HPV-16 in situ hybridization and p16 immunohistochemistry. Patients with HPV-positive tonsillar cancers who had undergone bilateral tonsillectomies were selected for more complete mapping of viral integration. Results: HPV-16 was detected in 38 of the 176 (22{\%}) cases by in situ hybridization. When stratified by site of origin, HPV-16 was detected in 37 of 45 cancers arising from the oropharynx but in only 1 of 131 tumors arising from nonoropharyngeal sites (82{\%} versus 0.8{\%}, P <0.00001). P16 expression was associated with the presence of HPV-16: 31 of 38 HPV-positive tumors exhibited p16 expression, whereas only 9 of the 138 HPV-negative tumors were p16-positive (82{\%} versus 6{\%}, P <0.00001). In the bilateral tonsil sections, hybridization signals were strictly limited to the invasive cancers and associated dysplasias. P16 staining was widely distributed throughout the nonneoplastic crypt epithelium of individuals with and without tonsillar cancer. Conclusions: HPV-16 is strongly associated with carcinomas arising from the oropharynx, and integration is tightly coupled to the neoplastic process. Viral integration does not occur as a field alteration throughout normal tonsillar epithelium. P16 expression localizes to HPV-positive cancers, and is intrinsic to the specialized epithelium of the tonsillar crypts. For risk assessment, early cancer detection and disease surveillance, evidence of HPV-16 integration may represent a meaningful finding, whereas high p16 expression, by itself, may not.",
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