Relationship between telomerase activation and HPV 16/18 oncogene expression in squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix

Int J Gynecol Pathol. 2001 Apr;20(2):177-85. doi: 10.1097/00004347-200104000-00011.

Abstract

SILs (squamous intraepithelial lesions) comprise a wide spectrum of clinically and biologically heterogeneous lesions ranging from benign proliferations to precancerous lesions. Telomerase activation plays a critical role in cellular immortalization and might be important for malignant progression. The viral oncogenes E6 and E7 are the principal transforming genes of high-risk HPVs and are important in HPV-associated immortalization and neoplastic transformation. In this study we investigated the relationship between telomerase activity, telomerase RNA, and HPV 16/18 oncogene expression in low- and high-grade SILs and SCCs (squamous cell carcinomas) of the cervix uteri. Telomerase activity was examined by the TRAP-assay and expression of the telomerase RNA (hTR) and HPV 16/18 E6/E7 oncogenes by RNA/RNA-in situ hybridization (ISH). The associated HPV-type was determined by PCR. Telomerase activity was observed in 25/29 (86%) SCCs, 31/41 (76%) high-grade SILs, 6/14 (43%) low-grade SILs, and 1/28 (3.6%) normal cervical tissues. Expression of hTR and viral oncogenes increased significantly with histopathologic severity of the lesion (p < 0.0001). A correlation was found between telomerase activity and intensity of viral oncogene expression. These findings suggest that telomerase activation occurs early in cervical carcinogenesis and is predominantly found in high-grade SILs and cervical SCCs. Our findings support current experimental data that suggest that telomerase is at least partially activated by viral oncogenes of high-risk HPV types. Telomerase activity with concomitant strong viral oncogene expression might therefore characterize a subset of lesions that are at risk for malignant progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell* / enzymology
  • Carcinoma, Squamous Cell* / virology
  • Cervical Intraepithelial Neoplasia* / enzymology
  • Cervical Intraepithelial Neoplasia* / virology
  • DNA, Viral / analysis*
  • Enzyme Activation
  • Female
  • Gene Expression
  • Humans
  • Neoplasm Metastasis
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / enzymology
  • Papillomavirus Infections / virology
  • RNA, Messenger / analysis
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Tumor Virus Infections / diagnosis
  • Tumor Virus Infections / enzymology
  • Tumor Virus Infections / virology
  • Uterine Cervical Neoplasms* / enzymology
  • Uterine Cervical Neoplasms* / virology

Substances

  • DNA, Viral
  • RNA, Messenger
  • Telomerase