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

SILs (squamous intraepithelial lesions) comprise a wide spectrum of clinica lly and biologically heterogeneous lesions ranging from benign proliferatio ns 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 neoplasti c transformation. In this study we investigated the relationship between te lomerase activity, telomerase RNA, and HPV 16/18 oncogene expression in low - and high-grade Sns and SCCs (squamous cell carcinomas) of the cervix uter i. 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 hybr idization (ISH). The associated HPV-type was determined by PCR. Telomerase activity was observed in 25/29 (86%) SCCs, 31/41 (76%) high-grade SILs, 6/1 4 (43%) low-grade SILs, and 1/28 (3.6%) normal cervical tissues. Expression of hTR and viral oncogenes increased significantly with histopathologic se verity of the lesion (p < 0.0001). A correlation was found between telomera se activity and intensity of viral oncogene expression. These findings sugg est that telomerase activation occurs early in cervical carcinogenesis and is predominantly found in high-grade SILs and cervical SCCs. Our findings s upport current experimental data that suggest that telomerase is at least p artially activated by viral oncogenes of high-risk HPV types. Telomerase ac tivity with concomitant strong viral oncogene expression might therefore ch aracterize a subset of lesions that are at risk for malignant progression.