3q26 Amplification Is an Effective Negative Triage Test for LSIL: A Historical Prospective Study

Abstract

BackgroundWomen with low grade squamous intraepithelial lesions (LSIL) at cervical cancer screening are currently referred for further diagnostic work up despite 80% having no precancerous lesion. The primary purpose of this study is to measure the test characteristics of 3q26 chromosome gain (3q26 gain) as a host marker of carcinogenesis in women with LSIL. A negative triage test may allow these women to be followed by cytology alone without immediate referral to colposcopy.Methods and FindingsA historical prospective study was designed to measure 3q26 gain from the archived liquid cytology specimens diagnosed as LSIL among women attending colposcopy between 2007 and 2009. 3q26 gain was assessed on the index liquid sample; and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were measured at immediate triage and at 6–16 months after colposcopic biopsy. The sensitivity of 3q26 gain measured at immediate triage from automated and manually reviewed tests in 65 non-pregnant unique women was 70% (95% CI: 35, 93) with a NPV of 89% (95% CI: 78, 96). The sensitivity and NPV increased to 80% (95% CI: 28, 99) and 98% (95% CI: 87, 100), respectively, when only the automated method of detecting 3q26 gain was used.Conclusions3q26 gain demonstrates high sensitivity and NPV as a negative triage test for women with LSIL, allowing possible guideline changes to routine surveillance instead of immediate colposcopy. Prospective studies are ongoing to establish the sensitivity, specificity, PPV and NPV of 3q26 gain for LSIL over time.

Prediction of outcome in patients with low‐grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC

“…The current study data regarding ICN of TERC genes in normal samples (2%), LSIL (31%) specimens, and HSIL (85%) specimens were comparable to those in the literature . This is also in keeping with previous reports, in which an ICN of TERC genes improved the sensitivity for the detection of underlying high‐grade lesions in patients with LSIL . According to the recent study by Chen et al, TERC analysis showed a higher sensitivity (90%) and specificity (89.6%) than conventional cytology (sensitivity: 84% and specificity: 64.3%) for the detection of ≥CIN2 lesions .…”

“…This so‐called stage differentiation (ie, the discrimination between cervical lesions of different grades using TERC assessment) has been confirmed in several studies . These previous publications assessing the value of TERC assessment in cervical cytology are listed in Table . This table illustrates that the evaluation criteria differ greatly among the studies (eg, the number of evaluated cells may range between 25 cells and 4996 cells).…”

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

“…The percentage of successfully hybridized samples was 100% in our study, considerably higher than in other studies [30,31,32,33]. In keeping with previous studies, we found a significant correlation (95%) between the HPV-DNA test and hTERC FISH.…”

“…Several studies postulated the essential role of 3q26 during the progression of cervical lesions to invasive cancer [24], but the application of molecular techniques able to identify hTERC gene amplification in a clinical setting is still evolving [29,30,31,32,33]. Our goal was to evaluate 3q26 hTERC FISH analysis on liquid-based cervical samples, in order to establish its accuracy as a predictive test and its feasibility for routine application.…”

Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting low-grade squamous intraepithelial lesions — A Taiwanese Gynecologic Oncology Group (TGOG) study

“…Many other triage methods for the cytological diagnoses of LSILs have been reported, including testing for specific oncogenic HPV types such as type 16 [10], HPV mRNA testing [11], 3q26 gain fluorescence in-situ hybridization testing [12], and measuring integration and quantifying markers of cell cycle aberration such as p16ink4a alone or in combination with Ki67 immunostaining [13,14]. Among these methods, the use of p16ink4a immunostaining has been extensively investigated.…”