Relation Between HPV-DNA and Expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA Ploidy in Early Cervical Carcinoma: Correlation With Clinical Outcome

Oncol Rep. 2004 Jul;12(1):169-76. doi: 10.3892/or.12.1.169.


The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.

MeSH terms

  • Aneuploidy*
  • Base Sequence
  • Cell Cycle Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA Primers
  • DNA Probes
  • DNA, Neoplasm / genetics
  • DNA, Viral / genetics*
  • Female
  • Genes, bcl-2 / genetics*
  • Genes, p53 / genetics*
  • Humans
  • Ki-67 Antigen
  • Neoplasm Staging
  • Papillomaviridae / genetics*
  • Ploidies*
  • Retrospective Studies
  • Treatment Outcome
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA Primers
  • DNA Probes
  • DNA, Neoplasm
  • DNA, Viral
  • Ki-67 Antigen