Methylation of CpG sites in the upstream regulatory region, physical status and mRNA expression of HPV-6 in adult-onset laryngeal papilloma

• Published in: Oncotarget Vol. 8; no. 49; pp. 85368 - 85377
• Main Authors: Deng, Zeyi, Ikegami, Taro, Kiyuna, Asanori, Zhang, Chunlin, Zhang, Tao, Matayoshi, Sen, Uehara, Takayuki, Maeda, Hiroyuki, Suzuki, Mikio, Ganaha, Akira
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 17.10.2017
• Subjects: Research Paper; adult-onset laryngeal papilloma; physical status; human papillomavirus-6; methylation; mRNA expression
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.19898

The methylation status of HPV-6 upstream regulatory region (URR) in adult-onset laryngeal papillomatosis (AO-LP) remains unclear. The purpose of this study was to investigate the methylation status of URR and the physical status of HPV-6, as well as the dynamic variations of viral load and mRNA expression in AO-LP. We examined 18 specimens from 11 patients with AO-LP by real-time polymerase chain reaction (PCR), bisulfite-sequencing PCR, and amplification of papilloma oncogene transcripts. HPV-6 was identified in 9 of 11 patients (81.8%), and all the 15 specimens derived from 9 HPV-6-positive cases contained only episomal HPV-6 transcripts with intact . Three HPV-6-positive patients developed recurrent lesions, and HPV-6 copy numbers and mRNA expression decreased after surgical treatment. Among the 96 CpG sites (16/case), 67 (69.8%) were unmethylated, while 23 (30.2%) were heterogeneous (≥ 1 methylated CpG clone). High viral loads and episomal status of HPV-6 were frequently observed in AO-LP; thus, persistent mRNA expression of LR-HPV-6 may be associated with AO-LP recurrences. Hypomethylation and scattered patterns of methylated CpGs at the URR of HPV-6 were identified in AO-LP.