Mutation detection of E6 and LCR genes from HPV 16 associated with carcinogenesis

Asian Pac J Cancer Prev. 2015;16(3):1151-7. doi: 10.7314/apjcp.2015.16.3.1151.

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 European variant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistent viral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samples from Cordoba, in order to detect the circulating lineages and analyze the presence of mutations that could be correlated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged to the E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences was G7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contribute to carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of the samples, associated with increased risk of persistent infection. The high detection rate of the European lineage correlated with patterns of human migration. This study emphasizes the importance of recognizing circulating lineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlated to the development of carcinogenic lesions.

MeSH terms

  • Carcinogenesis
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / virology
  • DNA, Viral / genetics
  • Female
  • Follow-Up Studies
  • Human papillomavirus 16 / genetics*
  • Humans
  • Locus Control Region / genetics*
  • Mutation / genetics*
  • Neoplasm Grading
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology
  • Phylogeny
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Repressor Proteins / genetics*
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / virology

Substances

  • DNA, Viral
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins