HPV16 E6*II gene expression in intraepithelial cervical lesions as an indicator of neoplastic grade: a pilot study

Med Oncol. 2014 Mar;31(3):842. doi: 10.1007/s12032-014-0842-6. Epub 2014 Jan 17.

Abstract

Integration of the HPV genome into a host cell DNA leads to the deregulated overexpression of the viral E6 and E7 oncoproteins, and this is a key factor for progression from low-grade cervical lesions to high-grade lesions and invasive cervical cancer. The aim of our study was to analyze the expression levels of HPV E6*I/E6*II and E7 genes in cervical neoplasia of different grades. The analysis involved 10 low-grade squamous intraepithelial lesions (CIN1), 15 high-grade lesions (CIN2 and CIN3), as well as normal cytology samples (n=10). HPV genotyping was done using RealLine HPV 16/18 kit. The expression analysis was performed in real-time PCR assay using gene-specific primers and SYBR Green. HPV16 DNA was found in 65.71% patients, including also normal cytology samples. The increased expression level of E6*I was observed in 12 (34.3%) patients. The expression of E6*II was increased in 10 (28.6%) samples, and E7 overexpression was found in 14 (40%) patients. Significant positive correlation was observed between the amount of HPV16 DNA and the levels of E6*I and E6*II expression. There were no statistically significant differences in expression levels of the studied genes between the groups (CIN1 vs. CIN2/CIN3 vs. normal cytology). Statistically significant differences were found in CIN2/CIN3 group, with the higher expression of E6*II as compared with E6*I. We suggest that the expression level of E6*II gene might be used as an indicator of cervical cancer severity, in patients with high-grade cervical neoplasia, but these observations need to be confirmed in a larger patient cohort.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Case-Control Studies
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • DNA, Viral / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Human papillomavirus 16 / genetics*
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Pilot Projects
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology
  • Young Adult

Substances

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