Abstract
BackgroundThe consistency of pathologists in the diagnosis of cervical intraepithelial neoplasia (CINs) is not ideal, especially between low- and high-grade squamous intraepithelial lesions (LSIL and HSIL). This study was aimed to explore efficient strategies for the grading of CINs.MethodsThe medical records of patients with high risk human papillomavirus (HR-HPV) infections who had underwent cervical biopsy or conization from April 2018 to April 2019 in Beijing Chao-Yang Hospital were collected and examined. The HR-HPV E6/E7 mRNA in the tissues of patients with CINs was detected using RNAscope chromogenic in situ hybridization (RISH). Immunohistochemistry (IHC) was performed to evaluate the expression of p16INK4a (P16) and Ki67.ResultsHR-HPV E6/E7 mRNA signals were detected in 3/27 (11.1 %) of CIN 1, and in 32/33 (97.0 %) of CIN 2/3. Most of the staining patterns (27/32, 84.4 %) had a full-thickness epithelial layer staining with weak-to-strong nuclear and cytoplasmic dot-like signals in CIN 2/3, and there were also few special staining patterns that were significantly different from the others. A number of indicators were compared between LSIL and HSIL. There were statistically significant differences in E6/E7 mRNA, p16, Ki67 and cytology between the two groups (P < 0.05). According to the logistic regression analysis, merely E6/E7 mRNA positivity was significantly associated with CIN2/3 (OR: 52.53, 95 % CI, P < 0.05). In the detection of CIN 2/3, the sensitivity and specificity of HPV E6/E7 mRNA alone was not significantly inferior to that of its different combinations with Ki67, p16 and cytology (all, P > 0.05).ConclusionsRISH is efficient in grading of CINs. The HPV E6/E7 mRNA expression might reflect the phase HPV infections, and its positive pattern might predict the development direction of CINs, providing the possibility to realize more accurate treatments for patients.
Highlights
The consistency of pathologists in the diagnosis of cervical intraepithelial neoplasia (CINs) is not ideal, especially between low- and high-grade squamous intraepithelial lesions (LSIL and High-grade squamous intraepithelial lesion (HSIL))
According to the 2012 American Society for Colposcopy and Cervical Pathology (ASCCP) revised guidelines for the treatment of CC screening abnormal results [19], patients with abnormal cytology, HR-HPV16/18 positive testing, persistent infection of the other subtypes of HR-Human papilloma virus (HPV), Atypical squamous cells of undetermined significance (ASC-US) and high risk human papillomavirus (HR-HPV) positive testing, and/or visible suspicious lesions were scheduled for colposcopy
The remaining 33 (55 %) women were diagnosed with HSIL, which included CIN2 (17 cases) and CIN3 (16 cases), respectively
Summary
The consistency of pathologists in the diagnosis of cervical intraepithelial neoplasia (CINs) is not ideal, especially between low- and high-grade squamous intraepithelial lesions (LSIL and HSIL). This study was aimed to explore efficient strategies for the grading of CINs. Cervical cancer (CC) is one of the most common malignant tumors in women. The consistency of pathologists in the diagnosis of CINs remains unideal. For CIN2, the reported diagnostic consistency of independent pathologists is less than 50 % [5, 6]. Due to the lack of reproducible histological distinctions and accurate biomarkers that could efficiently define the distinct intermediate state of CIN2, a two-tier system of low- and high-grade squamous intraepithelial lisions (LSIL and HSIL, respectively) has been recommended. CIN2 is no longer regarded as an independent histological subtype [3]
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