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Genotypespecific methylation of HPV in cervical intraepithelial neoplasia
Yaw-Wen Hsu,Rui-Lan Huang,Po-Hsuan Su,Yu-Chih Chen,Hui-Chen Wang,Chi-Chun Liao,Hung-Cheng Lai 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.4
Objective: Hypermethylation of human papillomavirus (HPV) and host genes has beenreported in cervical cancer. However, the degree of methylation of different HPV typesrelative to the severity of the cervical lesions remains controversial. Studies of the degree ofmethylation associated with the host gene and the HPV genome to the severity of cervicallesions are rare. We examined the association of methylation status between host genes andlate gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings. Methods: Cervical brushings from 147 HPV-infected patients were obtained. The samplescomprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), andCIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measuredusing bisulfite pyrosequencing and quantitative methylation-specific polymerase chainreaction (PCR). Results: The degree of methylation of L1 in HPV16, 18, and 52 was associated with theseverity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and0.026, respectively). Methylation of most HPV types except HPV52 (r<−0.1) was positivelycorrelated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2. Conclusion: Our study showed that the degree of L1 methylation of HPV16, 18, and 52but not 58 is associated with the severity of cervical lesions. The association betweenHPV methylation and host gene methylation suggests different responses of host cellularepigenetic machinery to different HPV genotypes.