Characterization of the methylation patterns in human papillomavirus type 16 viral DNA in head and neck cancers

Il Seok Park, Xiaofei Chang, Myriam Loyo, Gaosong Wu, Alice Chuang, Myoung Sook Kim, Young Kwang Chae, Sofia Lyford-Pike, William H. Westra, John R. Saunders, David Sidransky, Sara Isabel Pai

Research output: Contribution to journalArticle

Abstract

Human papillomavirus (HPV) type 16 can integrate into the host genome, thereby rendering the viral coding genes susceptible to epigenetic modification. Using bisulfite genomic sequencing, we determined the methylation status of all 110 CpG sites within the viral epigenome in advanced stage III/IV HPV-16-associated head and neck cancers. We found that the viral genome was hypomethylated in the majority of head and neck cancers, in particular within the viral regulatory region, long control region (LCR), which controls transcription of the E6 and E7 oncogenes. The hypomethylation status of LCR correlated with detectable levels of E6 and E7 expression, which suggests that the tumors may still be dependent on these viral oncogenes to maintain the malignant phenotype. In addition to the methylation status of LCR, we report other potential factors which may influence intratumoral E6 and E7 expression including viral copy number and integration site. We were able to detect the viral epigenetic alterations in sampled body fluids, such as serum and saliva, which correlated with the changes observed in the primary tumors. Because viral epigenetic changes occur in the setting of viral integration into the human genome, the detection of methylated HPV genes in the serum and/or saliva may have diagnostic potential for early detection strategies of viral integration and assessment of risk for cancer development in high-risk individuals. Our findings also support continued targeting of the E6 and/or E7 antigens through various vaccine strategies against HPV-associated cancers.

Original languageEnglish (US)
Pages (from-to)207-217
Number of pages11
JournalCancer Prevention Research
Volume4
Issue number2
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Park, I. S., Chang, X., Loyo, M., Wu, G., Chuang, A., Kim, M. S., Chae, Y. K., Lyford-Pike, S., Westra, W. H., Saunders, J. R., Sidransky, D., & Pai, S. I. (2011). Characterization of the methylation patterns in human papillomavirus type 16 viral DNA in head and neck cancers. Cancer Prevention Research, 4(2), 207-217. https://doi.org/10.1158/1940-6207.CAPR-10-0147