Abstract
Approximately 20–40% of high-grade Cervical Intraepithelial Neoplasia (CIN) regresses spontaneously, but the natural prognosis of an individual lesion is unpredictable. Gain of the chromosomal 3q region, which contains the human telomerase RNA gene on 3q26, is found in CIN lesions and cervical carcinoma and shows correlation with disease grade. The aim of this study is to assess whether 3q26 gain as a single genetic marker can predict the natural prognosis of high-grade CIN, by performing a review of the literature and pilot study. A literature review was conducted. Additionally, we performed a pilot study in 19 patients with histologically confirmed high-grade CIN lesions who were followed for a mean of 115 days, after which loop excision was performed. Fluorescent in situ hybridization analysis was performed on the initial diagnostic biopsies to determine gain of 3q26. Eight studies were included in the literature overview, with a total of 407 patients. Of these, only 22 patients had high-grade lesions. All studies found an association between 3q26 gain and disease prognosis. Positive predictive values (PPV) ranged from 50 to 93%, negative predictive values (NPV) ranged from 75 to 100%. Only five out of 155 patients (3.2%) without 3q26 gain showed disease persistence or progression. In our pilot study on 3q26 gain in high-grade CIN, the PPV of 3q26 gain for disease persistence was 67%, the NPV 100%. All four patients without 3q26 gain showed disease regression. In conclusion, the absence of 3q26 gain in diagnostic biopsies may be applied to identify high-grade CIN lesions with a high probability of disease regression.
Highlights
Patient PopulationHigh-grade Cervical Intraepithelial Neoplasia (CIN) is caused by Human Papillomavirus (HPV)-infection and is considered to be the precursor of cervical carcinoma [1]
The association between 3q gain and cervical oncogenesis may be caused by amplification of the human telomerase RNA gene, which is localized on the 3q26 locus
Several studies have addressed the prognostic properties of 3q26/ Human telomerase RNA gene (hTERC) gain in the natural prognosis of CIN, but most studies focussed on low-grade lesions and/or evaluated 3q gain in cytological specimen
Summary
Patient PopulationHigh-grade Cervical Intraepithelial Neoplasia (CIN) is caused by Human Papillomavirus (HPV)-infection and is considered to be the precursor of cervical carcinoma [1]. Cervical oncogenesis is characterized by several genetic effects, among which are genomic instability, chromosomal aberrations and integration of viral DNA into the host genome. Markers of these processes have been identified as potential diagnostic or prognostic biomarkers in the diagnosis and prognosis of CIN [10, 11]. Among these is chromosomal region 3q gain, which is frequently found in cervical carcinomas and its precursor lesions [12]. The goal of this study is to provide an overview of the literature on the prognostic properties of 3q26/hTERC gain in the natural prognosis of CIN and to investigate the predictive properties of 3q26 gain in high-grade CIN
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