engleski

Gene promoter methylation in HPV 53 and HPV 66 positive woman of different age groups

High-risk human papillomavirus (HPV) types 16, 18, 31, 33, 35, 45, 52, and 58 are commonly found in cervical cancer worldwide. In Croatia, the prevalence of those HPV types decrease with age, while those of the other, rarer HPV types increase. Thus, HPV53 and HPV66 were surprisingly abundant in the age group >55, being found in 10.3% and 3.7% of cases, respectively, while the prevalence of the common types was lower (HPV31 found in 7.4% cases ; HPV16 and HPV33 found in 4.4% cases each ; HPV6/11, 52, 58 and 45 found in <3.7% cases each). Worldwide studies on women with normal cytology and cervical cancer showed that HPV53 and HPV66 are relatively common in normal cervical specimens and very rarely found in invasive cervical cancers (<1%) and there still have unclear carcinogenic potential. Therefore, in this study, we focused on HPV53 and HPV66 positive cervical samples and analyzed the methylation status by methylation specific PCR of different host cell gene promoters to clarify the carcinogenicity of those types. Correlation between gene promoter methylation profiles of cervical samples and cytological diagnosis was assessed, as well as with age groups. Elevated methylation pattern for almost all tested gene promoters were found in women age >55 years compared to younger women, both groups being HPV53 or HPV66 positive. The highest methylation was found in RARβ2, CDH1 and DAPK1 gene promoters. Moreover, the methylation of CCNA1, TWIST and hTERT2 gene promoters was greater than those expected for a particular diagnosis. These findings point out that HPV53 or HPV66 show higher carcinogenic potential with increasing age.

HPV; DNA methylation

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