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Aim: To examine whether the detection of either telomerase and its components or high risk human papillomavirus (HPV) are of value in predicting the presence of cervical intraepithelial neoplasia (CIN) grade II/III in women referred because of cervical cytology reports showing at most moderate dyskaryosis. Methods: Cervical scrapings of 50 women referred with cytological borderline, mild, or moderate dyskaryosis were analysed. Telomerase activity was assessed by a commercially available telomere repeat amplification protocol assay and its components human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) were assessed by reverse transcriptase polymerase chain reaction (PCR). HPV was detected by GP5+/6+ PCR enzyme immunosassay. Histological findings on colposcopy guided biopsies or excised cervical tissue were regarded as the final pathological diagnosis. The sensitivity and specificity for detecting CIN II/III were calculated. Results: Twenty eight women were diagnosed with CIN II/III. Telomerase activity was detected in none, hTR in 88%, hTERT in 23%, and high risk HPV was detected in 79% of these women. As a diagnostic test none of the described analyses combined a sensitivity of at least 90% with a specificity > 90%. Despite the small numbers, calculation of the 95% confidence intervals excluded a combined sensitivity and specificity of at least 90% for all of the evaluated parameters. Conclusions: Neither detection of telomerase or its components, nor detection of high risk HPV seem suitable for the triage of women with borderline, mild, and moderate cytological dyskaryosis. C ervical cancer, which develops from cervical intraepithelial neoplasia (CIN), is an important cause of death in women worldwide.1 A CIN lesion can either regress, persist, or progress towards (micro)invasive carcinoma. Most low grade CIN lesions (CIN I) will regress, whereas in the long term 12-40% of high grade CIN lesions (CIN II/III) progress to squamous cell carcinoma.2 3 Because there are no markers to identify those lesions that will progress, clinicians have felt compelled to treat at least all CIN II/III lesions.Cytomorphological examination of cervical smears is the most widely applied screening method for cervical cancer and its precursors. The disadvantages are the high numbers of false negative and false positive cervical smears. Cervical cytology alone is a good predictor for the presence of CIN II/III when it shows severe dyskaryosis or carcinoma in situ. CIN II/III or cancer was found in 89-93% of women with these severely abnormal smears.4 5 In contrast, 51-58% of women with mild or moderate dyskaryosis on cytology are diagnosed with CIN II/III. 5 6 All of the women with cytological mild or moderate dyskaryosis are subjected to colposcopic evaluation, implying an overshoot of diagnostic procedures. 7 8 Thus, there is a need for parameters in cervical scrapings that could more accurately predict the presence of CIN II/III or cancer in women with borderline, mild, or moderate dyskaryotic smears.

The limited capacity to divide is one of the major differences between normal somatic cells and cancerous cells. This 'finite life span' of somatic cells is closely linked to loss of telomeric DNA at telomeres, the 'chromosome caps' consisting of repeated (7TAGGG) sequences., In more than 85% of advanced cancers, this telomeric attrition is compensated by telomerase, 'the immortality enzyme', implying that telomerase inhibition may restore mortality in tumor cells. This review discusses the progress in research on the structure and function of telomeres and the telomerase holoenzyme. In addition, new developments in telomere/telomerase targeting compounds such as antisense oligonucleotides and G-quadruplex stabilizing substances, but also new telomerase expression-related strategies such as telomerase promoter-driven suicide gene therapy and telomerase immunotherapy will be presented. It will be discussed how these data can be implemented in telomerase-directed therapies.

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