Value of high-risk HPV E6/E7 mRNA in situ hybridization in grading of cervical intraepithelial neoplasia

Abstract

Objective: To investigate the value of high-risk HPV E6/E7 mRNA in situ hybridization in the grading of cervical squamous intraepithelial neoplasia (CIN). Methods: A total of 261 cases with diagnosis of CIN and cervical squamous cell carcinoma (SCC) at west China University Second Hospital, Sichuan University from July 2019 to June 2020 were collected, including 60 cases of CIN1, 41 cases of CIN2, 51 cases of CIN3, 72 cases of SCC, and 37 cases of normal cervical control tissue (10 HPV negative and 27 HPV positive). All pathologic tissues were made into tissue microarrays, and HE staining, HPV E6/E7 mRNA in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining were performed respectively. The staining was assessed by light microscopy, and the positive rate and positive pattern were analyzed statistically. Results: HPV mRNA ISH in CIN1 mainly showed spot staining in predominantly basal to mid-epithelial layers (≤BME) with a diffuse nuclear signals in the superficial layer (supD), that is, the pattern of ≤BME+supD; in CIN2, it mainly showed spot staining in predominantly basal to above mid-epithelial but not the full layer (>BME) and some cases with supD staining, that is, the pattern of>BME+supD; In CIN3, the mainly pattern was >BME, and the spot staining was distributed throughout the epithelium. In CIN1, CIN2 and CIN3, there were significantly statistical differences among the above three staining patterns (P<0.05). Conclusions: HPV mRNA ISH contributes to the accurate diagnosis and grading of CIN, and has better specificity than p16 IHC staining.