Human papillomavirus (HPV) E6/E7 mRNA as a triage test after detection of HPV 16 and HPV 18 DNA

Abstract

High-risk human papillomavirus (HPV) DNA detection provides high sensitivity but low specificity for moderate-grade cervical intraepithelial neoplasia or worse histological identification. A prospective study evaluated mRNA testing efficacy for predicting this histological diagnosis in case of HPV 16 and/or 18 DNA detection. A total of 165 endocervical samples harboring HPV 16 and/or 18 DNA were tested with NucliSENS-EasyQ® HPV E6/E7-mRNA-assay (Biomerieux, Marcy l´Etoile, France). Women with cytological alterations were referred to colposcopy (n = 111). Moderate-grade cervical intraepithelial neoplasia or worse was diagnosed in 25.8% of women presenting atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions and in 89.8% of women with high-grade squamous intraepithelial lesions. mRNA sensitivity was 81.3% and 84.1%, respectively. Specificity was 52.2%, and 80.0%, respectively. Negative predictive value (NPV) was 88.9% in undetermined or low-grade squamous lesions. Positive predictive value (PPV) was 97.4% in high-grade squamous lesions. mRNA reduced colposcopies by 44.3% in undetermined or low-grade squamous lesions. Direct treatment of mRNA-positive cases reduced 77.5% of colposcopies in high-grade squamous lesions. Women without cytological alterations were followed for 18 months (n = 35), and moderate-grade cervical intraepithelial neoplasia or worse was diagnosed in 34.3%; mRNA sensitivity and specificity were 83.3% and 86.9%, respectively. PPV and NPV were 76.9% and 90.9%, respectively for predicting moderate-grade cervical intraepithelial neoplasia or worse in 18 months. mRNA reduced the number of visits for follow-up in 62.2%. In conclusion, NucliSENS-EasyQ® HPV E6/E7-mRNA-assay (Biomerieux) can serve as a triage test in case of HPV 16 and/or 18 DNA detection.

Expression of human papillomavirus E6 and E7 oncoprotein mRNA in women with low-grade squamous intraepithelial lesions or less

“…The prevalence statistics were a little below those from a study by Perez Castro et al (2013); a prospective analysis revealed the corresponding results from their analysis to be 37.8, 55.7 and 77.5%. A follow-up investigation revealed that nearly 26% of the women with ASC-US or LSIL cytologies in that study had moderate/severe intraepithelial neoplasia.…”

Assessment of human papillomavirus E6/E7 oncogene expression as cervical disease biomarker

“…It was proved that E6/E7 mRNA positivity rate was higher in women with high-grade lesion than in samples with low-grade lesion or without lesion [8, 19, 26]. Besides, E6/E7 mRNA negativity rate was higher in women without lesion which means the possibility of an episomal state of the virus and effective regulation of transcription, which makes more likely spontaneous clearance of the infection.…”

Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection

“…The NucliSENS EasyQ HPV assay (BIOMÉRIEUX Italia S.p.A) is a real‐time nucleic acid amplification and detection assay for the qualitative determination of E6/E7 mRNA from five HPV types (16, 18, 31, 33, and 45), which are present in 97% of cervical cancers [Muñoz et al, ; Bertuccio et al, ]. Currently there are no published studies using mRNA‐NucliSens‐EasyQ (Biomerieux) as a primary test in cervical cancer screening, but it could be very useful as a triage in cases of hrHPV DNA detection and negative cytology because of its high sensitivity and specificity for moderate‐grade cervical intraepithelial neoplasia or worse detection [Perez Castro et al, ].…”