Relationship between HPV 16, 18, 31, 33, 45 DNA detection and quantitation and E6/E7 mRNA detection among a series of cervical specimens with various degrees of histological lesions

J Med Virol. 2015 Aug;87(8):1389-96. doi: 10.1002/jmv.24157. Epub 2015 Apr 23.

Abstract

Better understanding of the correlation between high-risk HPV DNA testing, viral load quantitation, and E6/E7 mRNA detection is required. The aim of this study was to assess the relationship between these markers and the severity of cervical lesions. One-hundred and fifty one directed cervical specimens were analysed (normal, cervical intraepithelial neoplasia, and cancer). HPV types 16, 18, 31, 33, and 45 DNA detection and quantititation and E6/E7 mRNA detection were performed. DNA was detected in 87 (57.6%) samples and increased from 0% (normal) to 93.9% (cancer). E6/E7 mRNA was detected in 65 (43%) samples and increased with the severity of the lesions from 0% (normal) to 78.8% (26/33) (cancers) (P < 0.001). HPV DNA and E6/E7 mRNA detection were compared in the 141 samples harbouring HPV16, 18, 31, 33, or 45 infection: 45.4% (64/141) of specimens were DNA-/mRNA-, 46% (65/141) were DNA + /mRNA+ and 8.5% (12/141) were DNA + /mRNA-. The proportion of DNA + /mRNA+ specimens increased with the severity of the lesions (P < 0.001). All normal cervix specimens were DNA-/mRNA-. Among grade 2 cervical intraepithelial neoplasia, prevalence of DNA was higher than that of mRNA: 41.6% (5/12) versus 25% (3/12), whereas it was 79.3% (46/58) versus 62% (36/58) among grade 3 cervical intraepithelial neoplasia. Full concordance was observed in cancers as all the 26 DNA+ specimens were mRNA +. Median overall HPV load was higher in DNA + /mRNA+ than in DNA + /mRNA- specimens (1.41 × 10(6) vs. 9.1 × 10(2) copies per million cells, P < 0.001). Both E6/E7 mRNA detection and concordant DNA + /mRNA+ detection increases with the severity of the lesions and with the HPV DNA load.

Keywords: E6E7 mRNA; cervical intraepithelial neoplasia; genotyping; high-risk HPV load; papillomavirus.

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • Gene Expression Profiling
  • Humans
  • Middle Aged
  • Oncogene Proteins, Viral / biosynthesis*
  • Oncogene Proteins, Viral / genetics
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • Severity of Illness Index*
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology

Substances

  • Oncogene Proteins, Viral
  • RNA, Messenger
  • RNA, Viral