Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Abstract

Objective: This study was designed to evaluate whether the adjunct of human telomerase RNA component (hTERC) fluorescence in situ hybridization (FISH) analysis to cytological diagnosis and human papillomavirus (HPV)-DNA testing may serve as a predictive marker for distinguishing cervical lesions destined to regress from those at high risk of progression towards invasive cancer. Study Design: hTERC FISH analysis was performed on 54 residual liquid-based cytology specimens obtained from women referred to colposcopy for the detection of atypical squamous cells of undetermined significance or worse (ASCUS+) lesions. Histological diagnosis was considered the gold standard and cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) as the worst outcome. Results: Oncogenic HPV-DNA was found in 96.3% of the specimens. Among these, 38.5% revealed a CIN2+ diagnosis. hTERC gene amplification was detected in 37% of the cases; among these, 70% showed up as CIN2+. hTERC FISH analysis significantly improves the specificity and positive predictive value of HPV-DNA testing, thus differentiating patients with a CIN2+ diagnosis from those with a CIN2- diagnosis. Conclusions: Despite the limitation of a small study sample, our findings provide promising data, indicating the possible role of hTERC analysis in the assessment of the risk of developing cervical cancer. This approach would implement the specificity of DNA testing, avoiding overtreatment at the same time. Prospective follow-up studies are needed with the aim of introducing hTERC FISH into decision-making algorithms.

Genomic amplification of HPV, h‑TERC and c‑MYC in liquid‑based cytological specimens for screening of cervical intraepithelial neoplasia and cancer

“…The present study reported that h-TERC gene analysis had the highest specificity (81.76%) and the lowest misdiagnosis rate (18.24%). Additionally, the combination of TCT, HPV and h-TERC displayed 100% sensitivity and 98.11% specificity, suggesting h-TERC may be the principal gene in cervical carcinogenesis, which is in line with results from previous studies (19,27). It has been reported that the h-TERC gene is significantly upregulated in numerous cancer types (28,29).…”

Validation of the FAM19A4 / mir124-2 DNA methylation test for both lavage- and brush-based self-samples to detect cervical (pre)cancer in HPV-positive women

“…This approach will reduce over-referral, unnecessary colposcopies, and overtreatment of women without clinically meaningful HPV infections. Currently, various triage strategies for hrHPV-positive women have been considered including repeat cytology testing [15] , HPV16/18 genotyping [16] , [17] (and combinations thereof [15] , [18] ), HPV E7 mRNA analysis [19] , [20] , viral and/or host cell DNA methylation analysis [21] , [22] , [23] , p16/ki67 cytological dual staining [24] , [25] and analysis of host cell gene amplification such as TERC [26] , [27] . Of these, cytology, either or not combined with HPV16/18 genotyping analysis, is currently most widely accepted [15] , [28] .…”

Telomeres and Telomerase During Human Papillomavirus-Induced Carcinogenesis

“…A high level of hTERT expression with a low level of TGFBR2 (transforming growth factor-β receptor type II) expression correlated with poor prognosis in patients with cervical cancer [ 69 ]. Studies conducted by Zappacosta et al [ 70 ] have indicated the possible application of the hTERC analysis in the diagnostics of CIN2 lesions. Studies on a group of 54 women with ASCUS+ lesions showed that 96.3% had oncogenic HPV-DNA, and the expression of the hTERC gene was confirmed by fluorescence in situ hybridization (FISH) in more than 70% of women with CIN2+ lesions.…”