Quantitative determination of human telomerase reverse transcriptase messenger RNA expression in premalignant cervical lesions and correlation with human papillomavirus load

Abstract

Expression of human telomerase reverse transcriptase (hTERT) messenger RNA (mRNA) and human papillomavirus (HPV)-16 load were quantified using real-time polymerase chain reaction and correlated with cytological findings and the presence of HPV infection in cervical specimens. Human telomerase reverse transcriptase mRNA expression was evaluated in 15 (20.5%) of 73 specimens of atypical squamous epithelial cells of undetermined significance, in 62 (39.7%) of 156 low-grade squamous intraepithelial lesions (LGSILs), in 49 (96%) of 51 high-grade squamous intraepithelial lesions (HGSILs), and in 9 (20%) of 45 normal samples, whereas viral load was quantified in 52 (89.6%) of 58 samples infected with HPV-16. The mean levels of hTERT mRNA expression were 0.11 in normal tissue, 0.23 in atypical squamous epithelial cells of undetermined significance, 0.75 in LGSILs, and 2.5 in HGSILs. Thus, a significant increase in hTERT mRNA expression was observed with increasing degrees of cervical dysplasia. The HPV-16 load was significantly higher in samples of HGSIL than in those of LGSILs (P < .001). A significant correlation was observed between viral load and quantitative hTERT mRNA expression (r = 0.65; P < .05). Quantitative hTERT mRNA assessment showed 96% sensitivity and 100% negative predictive value for high-grade dysplasia, whereas the specificity and positive predictive value were 72% and 36.2%, respectively. It is suggested that quantitative hTERT has a very high sensitivity and negative predictive value, whereas the observed specificity was moderate, indicating that it cannot be used as a diagnostic marker but may be an adjunct in the management of women with high-grade cervical dysplasia. However, the final diagnosis must rely on the inclusion of clinical evaluation and additional assessment data.