Telomerase, Cervical Cancer, and Human Papillomavirus

Review of the available data indicates that telomerase is activated in the majority of cervical squamous cell carcinomas as it is in most malignant neoplasms. Telomerase activity can also be detected in some preneoplastic cervical lesions, but the significance of this in unclear, because nonneoplastic, proliferating epithelial cells also can have telomerase activity. The bias introduced by cytologic sampling methods can complicate the interpretation of results. Quantitative telomerase assays may be useful in distinguishing nonmalignant, physiologic activation of telomerase from malignant activation. Studies evaluating telomerase component (hTR or hTERT) expression by evaluation of RNA, mRNA, or antigen have yielded conflicting results, but the observation that many nonmalignant, nontelomerase active cells have detectable hTR and hTERT suggests that many cells express telomerase RNA and catalytic components, but do not have active telomerase. The implication is that a regulatory overlay must exist that controls telomerase activation. Activation of the enzyme in carcinogenesis could conceivably be a physiologic activation that normally accompanies cellular proliferation, a direct appropriation of telomerase activity by the neoplastic process, or both. The presence of inactive telomerase in many cells also raises the possibility of a noncatalytic function for the telomerase complex. An understanding of telomerase interaction with HPV infection in the pathogenesis of cervical neoplasia must await a further elaboration of telomerase regulation. Likewise, application of telomerase detection in cervical cancer screening programs must await a better integration of telomerase regulation in normal and specifically in HPV-infected squamous epithelial cells.