HPV16 E6 polymorphism in correlation to physical state of viral genome and risk of cervical cancer in women from the south of Poland
Abstract
The aim of this study was to analyse the correlation between HPV16 E6 variants and the physical status of viral genome (integrated, mixed, episomal) among patients with cervical cancer (n=40) and low-grade squamous intraepithelial lesions – LSIL (n=40).
The study was performed on 80 HPV16 positive samples. HPV16 E6 variants were identified using PCR and DNA sequencing. Nucleotide sequences of E6 were compared with the prototype sequence (EUR-350T). The physical state of HPV DNA was determined as a ratio of E2/E6 copies number per cell. Twelve different intratypic variants were identified as belonging to European (in 77 samples) and North-American 1 (in 3 samples) sublineages. The most prevalent non-synonymous variant was EUR-350G, which occurred with similar frequency in cervical cancer and LSIL. The frequencies of additional mutations in variants with EUR-350T or EUR-350G sequences differed significantly. For the first time, missense mutations G122A, C153T and G188A were discovered in EUR-350G variant. The integrated viral genome was predominant in women with cervical cancer. EUR-350T prototype was prevalent in the episomal form and non-synonymous mutations were observed significantly more often in the mixed and integrated forms.
In summary, European variants of HPV16 E6 dominated in both study groups (cancer and LSIL). The presence of EUR-350G favoured the occurrence of additional nucleotide changes. Although we have not shown the correlation between the HPV16 E6 variants and physical state of viral genome it has been shown that mutations, especially the non-synonymous ones, occur significantly more often in the mixed or integrated forms of viral DNA.
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