HPV18 E6/E7 Mutation and Their Association with The Expression Level of Tumor Suppressor Proteins p53 and pRb among Indonesian Women with Cervical Cancer
Abstract
BACKGROUND: The E6/E7 mutation contributes to the intra-typic variant of HPV18 which may differ in their oncogenic potential. E6 and E7 target the tumour suppressor protein p53 and pRb, respectively, and their degradation play a crucial role in cervical carcinogenesis. However, the prevalence of HPV18 E6/E7 variants among Indonesian women with cervical cancer has not been elucidated. Therefore, this study was conducted to characterize the HPV18 variants among Indonesian women with cervical cancer and their association with tumor suppressor protein p53 and pRb.
METHODS: A hundred Indonesian women with pathologically proven cervical cancer were consecutively recruited into the study. Polymerase chain reaction (PCR) was performed to detect HPV18 DNA E6 and E7 oncogenes using specific primers and the variants was determined through nucleotide sequencing. Expressions of p53 and pRb were analyzed through immunohistochemistry by using specific antibodies targeting p53 and pRB.
RESULTS: The rate of HPV18 positivity was 24%. The rate of E6 and E7 mutation was 45.4% and 59.1%, respectively. Those with E6 mutation had significantly higher expression of p53 and pRb as compared to those with wildtype E6 (p<0.05). Subjects with E7 mutation only had higher expression of pRb (p<0.05). Phylogenetic analysis revealed that 54.5% subjects had genetic sequences closely related to Asian lineages, particularly A1, A4, and A5 sublineage. Interestingly, 3 subjects had genetic sequences closely related to MK813921, a newly identified sequences. However, 45.5% subjects had distinct genetic sequences that did not related to the reference sequence used in this study.
CONCLUSION: E6 and E7 mutation was common among Indonesian women with HPV18 cervical cancer and associated with the level of tissue p53 and pRb expression.
KEYWORDS: HPV18 E6/E7, mutation, epidemiology, Indonesian women
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DOI: https://doi.org/10.18585/inabj.v17i1.3400
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