Abstract
BackgroundLow-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by colposcopy guided biopsy is recommended conservative follow-up, although some of these lesions are actually high-grade lesions, which are missed on an initial colposcopy. Therefore, in this work, we evaluate the potential role of miRNA detection in cervical exfoliated cells in a clinic-based population for predicting missed high-grade lesions in women diagnosed with LSIL/CIN1 after colposcopy-guided biopsy.MethodsA total number of 177 women with a diagnosis of LSIL/CIN1 obtained by colposcopy-guided biopsy were grouped into two categories according to the histology of the conization specimens: consistent LSIL/CIN1 group (surgical pathology consistent with colposcopic diagnosis) and missed high-grade lesion group (surgical pathology found high-grade lesion). The expression of eight miRNAs, such as miRNA195, miRNA424, miRNA375, miRNA218, miRNA34a, miRNA29a, miRNA16–2, and miRNA20a was detected by real time-quantitative polymerase chain reaction (RT-qPCR) in cervical exfoliated cells of the 177 patients. Pearson Chi-Square was used to compare the performance efficiency of patients’ characteristics. Nonparametric Man-Whitney U test was used to assess differences in miRNA expression. The receiver operating characteristic (ROC) curve was used to assess the performance of miRNA evaluation in detecting missed high-grade lesions.ResultsAmong the 177 women with biopsy-confirmed CIN1, 15.3% (27/177) had CIN2+ in the conization specimen (missed high-grade lesion group) and 84.7% (150/177) had CIN1-(consistent LSIL/CIN1 group). The relative expression of miRNA-195 and miRNA-29a in the missed high-grade lesion group was significantly lower than that in the consistent LSIL/CIN1 group. The relative expression of miRNA16–2 and miRNA20a in the missed high-grade lesion group was significantly higher than that in the consistent LSIL/CIN1 group. No significant difference was observed between these two groups regarding the other four miRNAs. Of these significant miRNAs, miRNA29a detection achieved the highest Youden index (0.733), sensitivity (92.6%), positive predictive value (46.2%), negative predictive value (98.3%) and higher specificity (80.7%) when identifying missed high-grade lesions.ConclusionsDetection of miRNA might provide a new triage for identifying a group at higher risk of missed high-grade lesions in women with colposcopy diagnosis of LSIL/CIN1.
Highlights
Low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by colposcopy guided biopsy is recommended conservative follow-up, some of these lesions are high-grade lesions, which are missed on an initial colposcopy
A total of 177 women with LSIL/CIN1 diagnosis obtained by colposcopy-guided biopsy and treated by conization of cervix within three months were included in the study
Cervical HR-Human papillomavirus (HPV) infection was found in 86.7% of consistent LSIL/CIN1 group and 100% of missed high-grade lesion group, and the difference was statistically significant
Summary
Low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by colposcopy guided biopsy is recommended conservative follow-up, some of these lesions are high-grade lesions, which are missed on an initial colposcopy. With the promotion of cervical cancer screening, more and more low grade lesions (histological low-grade squamous intraepithelial lesion -LSIL-, termed cervical intraepithelial neoplasia grade 1 -CIN1- in the prior edition of three-tier terminology), diagnosed by colposcopy guided biopsy, are detected. After a negative cervical biopsy, a normal first follow-up cytology provided a CIN3+ risk considered acceptable to recommend return to routine screening in 3 years. For women with antecedent HPV-positive/ASC-US (atypical squamous cells of undetermined significance) or LSIL, a single negative post-colposcopy co-testing reduced their risk to a level consistent with a 3-year return. For women with antecedent atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion(ASC-H)or equal or greater than high-grade squamous intraepithelial lesion(HSIL+), no single negative test result sufficed to reduce their risk to a level consistent with a 3-year return [7, 8]. LSIL/CIN1 diagnosed by colposcopy guided-biopsy is recommended to conservative follow-up [11, 12]
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