Mutation Detection of E6 and LCR Genes from HPV 16 Associated with Carcinogenesis

Abstract

Human papillomavirus (HPV) is responsible for one of the most frequent sexually transmitted infections.The first phylogenetic analysis was based on a LCR region fragment. Nowadays, 4 variants are known: African(Af-1, Af-2), Asian-American (AA) and European (E). However the existence of sub-lineages of the Europeanvariant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistentviral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samplesfrom Córdoba, in order to detect the circulating lineages and analyze the presence of mutations that could becorrelated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged tothe E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences wasG7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contributeto carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of thesamples, associated with increased risk of persistent infection. The high detection rate of the European lineagecorrelated with patterns of human migration. This study emphasizes the importance of recognizing circulatinglineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlatedto the development of carcinogenic lesions.

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