Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma

Mod Pathol. 2007 Feb;20(2):256-66. doi: 10.1038/modpathol.3800737. Epub 2006 Dec 22.

Abstract

Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend=0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; P<0.0001) compared with the unknown HPV types (OR, 2.87; 95% CI, 0.89-9.22; P=0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3 (51%) and carcinoma (71%) and integrated significantly more frequently in carcinoma than in CIN 2/3 (P=0.004). No significant differences in viral load were observed across the disease categories. Our findings suggest that selected genotyping for the eight oncogenic HPV types might be useful in separating women with a higher risk of CIN progression from those with a minimal risk. We also conclude that the HPV 16 integration status has potential to be a marker for risk assessment of CIN progression.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / pathology
  • Adenocarcinoma / virology*
  • Cervical Intraepithelial Neoplasia / blood
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / virology*
  • DNA, Viral / analysis
  • Female
  • Genotype
  • Human papillomavirus 16 / classification
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification*
  • Humans
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / pathology
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • Viral Load*
  • Virus Integration / genetics

Substances

  • DNA, Viral