Molecular etiology of second primary tumors in contralateral tonsils of human papillomavirus-associated index tonsillar carcinomas

Andrew W. Joseph, Takenori Ogawa, Justin A. Bishop, Sofia Lyford-Pike, Xiaofei Chang, Timothy H. Phelps, William H. Westra, Sara I. Pai

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objectives: For patients with tobacco-related head and neck squamous cell carcinoma (HNSCC), the occurrence of a second primary tumor (SPT) is an ominous development that is attributed to a field cancerization effect and portends a poor clinical outcome. The goal of this study was to determine whether patients with human papillomavirus (HPV)-related index tonsillar carcinomas can also develop SPTs in the contralateral tonsil, and to discern the molecular etiology of HPV-related tumor multifocality. Materials and methods: The surgical pathology archives of The Johns Hopkins Hospital were searched for all patients with primary HPV-related tonsillar squamous cell carcinoma who developed a synchronous or metachronous carcinoma in the contralateral tonsil. The HPV-16 E6 exon was sequenced from each independent cancer site to determine whether the tumor pairs harbored the same or a different HPV-16 variant. Results: Four patients with bilateral HPV-related tonsillar carcinomas were identified. In every case, the HPV DNA sequences derived from the index tumor and corresponding SPT were 100% concordant, indicating that the index and SPTs were caused by the same HPV-16 variant. Conclusion: For the small subset of patients with tonsillar carcinomas who develop SPTs in the contralateral tonsil, the index case and the SPT consistently harbored the same HPV variant. This finding suggests that HPV-related tumor multi-focality can be attributed either to independent inoculation events by the same virus, or by migration of HPV-infected cells from a single inoculation site to other regions of Waldeyer's ring.

Original languageEnglish (US)
Pages (from-to)244-248
Number of pages5
JournalOral Oncology
Volume49
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

Palatine Tonsil
Carcinoma
Human papillomavirus 16
Neoplasms
Surgical Pathology
Tobacco
Squamous Cell Carcinoma
Exons
Viruses

Keywords

  • Head and neck cancer
  • Human papillomavirus
  • Oropharyngeal cancer
  • Second primary tumor
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

Molecular etiology of second primary tumors in contralateral tonsils of human papillomavirus-associated index tonsillar carcinomas. / Joseph, Andrew W.; Ogawa, Takenori; Bishop, Justin A.; Lyford-Pike, Sofia; Chang, Xiaofei; Phelps, Timothy H.; Westra, William H.; Pai, Sara I.

In: Oral Oncology, Vol. 49, No. 3, 01.03.2013, p. 244-248.

Research output: Contribution to journalArticle

Joseph, Andrew W. ; Ogawa, Takenori ; Bishop, Justin A. ; Lyford-Pike, Sofia ; Chang, Xiaofei ; Phelps, Timothy H. ; Westra, William H. ; Pai, Sara I. / Molecular etiology of second primary tumors in contralateral tonsils of human papillomavirus-associated index tonsillar carcinomas. In: Oral Oncology. 2013 ; Vol. 49, No. 3. pp. 244-248.
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abstract = "Objectives: For patients with tobacco-related head and neck squamous cell carcinoma (HNSCC), the occurrence of a second primary tumor (SPT) is an ominous development that is attributed to a field cancerization effect and portends a poor clinical outcome. The goal of this study was to determine whether patients with human papillomavirus (HPV)-related index tonsillar carcinomas can also develop SPTs in the contralateral tonsil, and to discern the molecular etiology of HPV-related tumor multifocality. Materials and methods: The surgical pathology archives of The Johns Hopkins Hospital were searched for all patients with primary HPV-related tonsillar squamous cell carcinoma who developed a synchronous or metachronous carcinoma in the contralateral tonsil. The HPV-16 E6 exon was sequenced from each independent cancer site to determine whether the tumor pairs harbored the same or a different HPV-16 variant. Results: Four patients with bilateral HPV-related tonsillar carcinomas were identified. In every case, the HPV DNA sequences derived from the index tumor and corresponding SPT were 100{\%} concordant, indicating that the index and SPTs were caused by the same HPV-16 variant. Conclusion: For the small subset of patients with tonsillar carcinomas who develop SPTs in the contralateral tonsil, the index case and the SPT consistently harbored the same HPV variant. This finding suggests that HPV-related tumor multi-focality can be attributed either to independent inoculation events by the same virus, or by migration of HPV-infected cells from a single inoculation site to other regions of Waldeyer's ring.",
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