Abstract
Aim: To assess the clinical significance of hTERC amplification for cervical cancer screening detected by fluorescence in situ hybridization (FISH) and compare it with that of current screening methods within the same group. Methods: A total of one hundred and nine women were recruited in this study. All of them had liquid-based thin-prep cytologic test (TCT), human papillomavirus (HPV) DNA testing and hTERC gene amplification analysis using interphase two-color FISH. In addition, colposcopically directed biopsy and/or cone biopsy were conducted for definite histopathologic diagnosis for each case. The optimal threashold of hTERC gene amplification by fluorescence in situ hybridization (FISH) were assecced by receiver operating characteristic (ROC) curve. The results of hTERC gene amplification analysis were compared with the cytological analysis, HPV DNA testing and those of subsequent biopsies. Results: Among the 109 patients, 18 were benign lesion, 17 were LSIL, 66 were HSIL and 8 were invasive carcinoma of cervix (ICC). Of them, hTERC-positive cases were found in 0.0% (0/18) of normal specimens, 11.8% (2/17) of LSIL, 72.7% (48/66) of HSIL and 100.0% (8/8) of ICC, respectively. The positive rate of hTERC gene amplification was significantly higher in HSIL and ICC compared with normal and LSIL (all P < 0.01).The optimal cut-off point of percentages of cells with hTERC amplification was determined as 5.5%. Using this threshold the hTERC test reached a much higher specificity(94.3%, 33/35) and a relatively lower sensitivity(77.0%, 57/74) to distinguish benign lesion and LSIL from HSIL and ICC in comparison with HR-HPV test (51.4%; 91.9%) and TCT (74.3%; 81.1%). Area Under the Curve revealed that hTERC amplification test performed more accurately (area under the curve = 0.857) compared to HPV test (area under the curve = 0.717) and cytology(area under the curve = 0.777) to discriminate HSIL or higher from LSIL or lower. This study also found a significant positive correlation between positive hTERC gain and HR-HPV infection, abnormal cytological or histopathologic lesions (all P < 0.01) in patients with cervical diseases. Conclusion: hTERC amplification testing may be a promising adjunct to screen women for cervical precancer or cancer with high specificity and accuracy.
Highlights
Cervical cancer remains one of the leading causes of female death, with an estimated 529,000 new cases and 274,000 deaths in 2008 worldwide, about 88% of which occur in developing countries [1]
fluorescence in situ hybridization (FISH) detection positive for human telomerase RNA component (hTERC) gene amplification was found in 0.0% (0/18) of normal specimens, 11.8% (2/17) of low-grade squamous intraepithelial lesion (LSIL), 74.2% (49/66) of high grade cervical squamous intraepithelial lesion (HSIL) and 100.0% (8/8) of invasive carcinoma of cervix (ICC), respectively
The positive rates of hTERC gene amplification were significantly higher in HSIL and ICC compared with normal and LSIL
Summary
Cervical cancer remains one of the leading causes of female death, with an estimated 529,000 new cases and 274,000 deaths in 2008 worldwide, about 88% of which occur in developing countries [1]. The widespread introduction of cervical screening programmes has been credited with reducing the incidence of invasive cervical cancer by 50% or more. Cervical cancer prevention is still an important and arduous task of the whole world, especially of developing countries. Several methods are recommended to screen for cervical cancer, such as the Pap smear, liquid-based cytology (LBC) and human papillomavirus (HPV) testing. The conventional Pap smear has been the principal screening test for cervical cancer since its introduction in the 1940s. It can only correctly identified 30% to 87% of women with precancerous lesions [3]. As an alternative to the Pap smear, LBC was approved by the OPEN ACCESS
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