Application of HPV E6/E7 mRNA detection in screening of moderately severe cervical intraepithelial neoplasia

Abstract

Objective This study aimed to explore the clinical value of human papilloma virus (HPV) E6/E7 mRNA tests in identifying precancerous lesions of the uterine cervix- cervical intraepithelial neoplasia 2 or more CIN2+ (CINⅡand CINⅢ). Methods This study is a cross-sectional survey design, between December 2011 to December 2013.The specimens were collected from the First People's Hospital of Huizhou and the Third People's Hospital of Huizhou in Department of Obstetrics and Gynecology outpatient and inpatient of cervical disease suspected patients, with thin-prep cytologic test (TCT) and histopathological results as reference, detected 345 patients of exfoliated cervical epithelial cells by using the branched DNA (b-DNA) technology to evaluate the application value of high risk HPV E6 / E7mRNA in the clinical diagnosis of CIN.Using spss 19.0 software for data analysis. Results (1)Compared with TCT, the positive rate of E6/E7 mRNA in 325 samples were grading by cytology as follows: no intraepithelial lesion cells (NILM) 21.1% (40/190), atypical squamous cells (ASC) 38.5% (15/39 ), low-grade squamous intraepithelial lesions (LSIL) 76.9% (30/39), atypical squamous cells can not exclude high-grade intraepithelial lesions (ASC-H) (8/10), high-grade squamous intraepithelial lesions (HSIL) 72.3% (34/47), TCT grades and HPV E6/E7 mRNA positive rate showed linear association (χ2=67.654, P<0.01; r=0.497, P<0.01); and with HPV E6/E7 mRNA copy number was also relevant (r=0.511, P<0.01). (2) Compared with pathological results, the positive rate of E6/E7 mRNA in 164 women samples were grading by pathology as follows: with NILM was 27.8%(10/36), with CIN Ⅰ was 65.9%(29/44), with CIN Ⅱ was 80.6%(54/67), and with CINⅢ was 82.4%(14/17), pathological grades and HPV E6/E7 mRNA positive rate showed a linear correlation (χ2= 26.426, P<0.01; r=0.438, P<0.01); and the number of copies correlated with the increase of pathological grades too(r=0.543, P<0.01). (3) Screening effectiveness analysis results showed, the sensitivity of HPV E6 / E7mRNA was 84.6% while TCT was 47.7%. The sensitivity and specificity were 40.0% and 91.1% respectively when HPV E6/E7 mRNA and TCT processed as sequential detection test. The CIN2 + (CIN Ⅱ and CIN Ⅲ) best diagnostic critical point of 890.26 copies/ml, was established using receiver operating characteristic (ROC) curve. The sensitivity and specificity were 58.5% and 93.7%, respectively. Conclusions The sensitivity of HPV E6/E7 mRNA test is better than TCT, the specificity is high in HPV E6/E7 mRNA and TCT processed as sequential detection test. Using the optimal cut-off value of ROC curve to detect CIN2+ has high sensitivity and specificity, so the detection of HPV E6/E7 mRNA may have some clinical value in screening and risk assessment of precancerous lesions of the uterine cervix.(Chin J Lab Med, 2015, 38: 532-536) Key words: Cervical intraepithelial neoplasia; Papillomaviridae; Oncogene proteins, viral; Papillomavirus E7 proteins