The physical state of HPV16 infection and its clinical significance in cancer precursor lesion and cervical carcinoma

J Cancer Res Clin Oncol. 2008 Dec;134(12):1355-61. doi: 10.1007/s00432-008-0413-3. Epub 2008 May 14.

Abstract

Purpose: Integration of high-risk human papillomavirus (HR-HPVs) into the host DNA has been proposed as a risk for cervical carcinogenesis. HPV-16 is the predominant high-risk type and its integration ration varied largely in different cervical cancer (CC) samples. The aim of this study was to evaluate the correlation between physical state of HPV16 infection and extent of cervical lesion, as well as the clinical significance of virus existing state.

Methods: A total of 252 cases of paraffin-embedded blocks derived from cancer precursor lesion and cervical carcinoma samples were detected by HC-II for HR-HPV infection. HPV16 infection was confirmed by PCR and immunohistochemistry for HPV16 E7 simultaneously. The physical state of HPV16 infection were assessed by PCR for 3 overlapping fragments in E2 gene and multiple PCR for E2 gene and E7 gene.

Results: The infection ratio of HR-HPV in normal cervical tissue, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cervical cancer were 15.0, 32.8, 54.3, 69.7, 93.8%, respectively. HR-HPV positive samples of 62.8% were infected with HPV16. The integration ratio of HPV16 in CIN III and cervical carcinoma were 35.7 and 58.1% respectively, both of which were significantly higher than that of CIN I and normal cervical tissues. The discrepancy was statistically significant (P < 0.05). Furthermore, it was observed that persistent virus infection and progression of cervical lesion were more common in CIN I with integrated HPV16 than that with episomal HPV16.

Conclusion: The integration ratio of HPV16 was accompanied by an increase in the grade of cervical lesion. The integrated state of HPV16 infection was strongly associated with persistent HPV infection and progression of cervical lesions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cervix Uteri / virology*
  • DNA, Viral / genetics
  • Female
  • Human papillomavirus 16 / genetics*
  • Humans
  • Middle Aged
  • Oncogene Proteins, Viral / genetics
  • Papillomaviridae
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology*
  • Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • Virus Integration / genetics*

Substances

  • DNA, Viral
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • oncogene protein E7, Human papillomavirus type 16