Establishment and characterization of a human papillomavirus type 16-positive tonsillar carcinoma xenograft in BALB/c nude mice

Head Neck. 2016 Mar;38(3):417-25. doi: 10.1002/hed.23918. Epub 2015 Jul 15.

Abstract

Background: Among head and neck cancers, human papillomavirus type 16 (HPV16) is associated with tonsillar carcinomas. Despite this, no HPV16-positive tonsillar cancer cell line has been established in nude mice.

Methods: Fresh tonsillar carcinoma biopsies were obtained from 23 patients and implanted subcutaneously into nude mice (BALB/c, nu/nu).

Results: After 7 months, one xenograft was established. The primary tumor harbored 2.7 copies (95% confidence interval = 2.4-2.9) of HPV16/cell and displayed 99.9% (7904/7906) nucleotide identity to HPV16 (EU118173.1). The xenograft showed increased methylation in two E2-binding sites of the HPV16 genome. Both episomal and integrated HPV16 were detected in the original tumor and in 14 xenografts from the second passage. From this passage, a viral load of 6.4 copies/cell (range = 4.6-9.6) and 3.7 (range = 1.0-5.5) E7-mRNA transcripts/HPV16-genome were detected.

Conclusion: This xenograft represents the first established HPV16-positive tonsillar tumor in nude mice and could provide an experimental system of HPV16-positive tonsillar cancers.

Keywords: carcinoma; human papillomavirus type 16 (HPV16); nude mice; tonsil; xenograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Female
  • Heterografts / virology*
  • Human papillomavirus 16 / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Papillomavirus Infections / virology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tonsillar Neoplasms / virology*
  • Viral Load