engleski

Elevated gene promoter methylation in HPV 53 and HPV 66 positive woman age 55 and over

Human papillomavirus (HPV) types HPV 16, 18, 31, 33, 35, 45, 52, and 58 are commonly found in cervical cancer worldwide. The prevalence of those cancer related common HPV types decrease with age among Croatian women with more or less abnormal cytological diagnosis, while those of the other, rarer HPV types increase. Upon genotyping, HPV 53 and HPV 66 were surprisingly abundant in the age group 55 and over, being found in 10.3% and 3.7% of cases, respectively. In addition, the prevalence of the common HPV types in this study group was lower compared to HPV 53 (HPV 31 found in 7.4% cases ; HPV types 16 and 33 found in 4.4% cases each) and HPV 66 (HPV types 6/11, 52, 58 and 45 found in less than 3.7% cases each). Furthermore, worldwide studies on women with normal cytology and cervical cancer showed that HPV 53 and HPV 66 are relatively common in normal cervical scrapes and very rarely found in invasive cervical cancers (less than 1%). Therefore the carcinogenic potential of HPV types 53 and 66 remains still unclear. In this study, we focused on HPV 53 and HPV 66 positive cervical samples and analyzed the methylation status of the promoter of different host cell genes. Methylation specific PCR (MSP) with primers specific for methylated and unmethylated forms of the gene was used to amplify bisulfite converted DNA. Correlation between gene promoter methylation profiles of cervical samples and cytological diagnosis was assessed. Among all tested gene promoters, methylation of CDH1, DAPK1, HIC1, RARβ2 and CCNA1 was extremely high, and, even much higher than expected for the actual diagnosis. Therefore, according to methylation patterns of examined host cell genes this study indicates that HPV types 53 and 66 seem to have a high carcinogenic potential.

DNA methylation; HPV; cervical cancer

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