Diagnostic performance of HPV E6/E7 mRNA testing towards HPV‐DNA testing and p16/Ki67 immunostaining as a biomarker of high‐risk HPV recurrence in Greek women surgically treated for their cervical lesions

Abstract Aim To evaluate the diagnostic performance of E6/E7 HPV‐mRNA overexpression towards HPV‐DNA testing and p16/Ki67 immunocytochemistry in a post‐op population to verify if this biomarker can be effectively used as indicator of successful cervical intraepithelial neoplasia (CIN) treatment. Methods Our study retrospectively analyzed 197 patients of our Colposcopy Clinic between January 2013 and September 2020 coming with an abnormal Pap smear suggestive for colposcopy, and after a series of follow‐ups including liquid‐based cytology (LBC) and punch‐biopsy sampling, there were surgically treated. LBC was used for cytology and molecular analysis of the three HPV‐related biomarkers. Results Six months after treatment, 93% of the HPV‐mRNA‐positive women became negative while this applied to only 80.2% of the HPV‐DNA‐positive women. HPV persistence was 6.9% at 6–12 months after treatment. The comparison among cytology, colposcopy, HPV‐DNA test, and HPV‐mRNA test after treatment revealed that the last one is the only with a strong correlation with actual severity (histology during treatment) ( ρ = 0.345, p = 0.006) implying that clinical cases with more severe CIN may have higher chances of unsuccessful treatment. HPV‐mRNA test had higher sensitivity (100%), specificity (96.88%), and positive predictive value (45.45%) for CIN2+ recurrent lesions when compared with HPV‐DNA testing (80%, 82.81%, 10.81% respectively) and p16/Ki67 immunocytochemistry (80%, 95.83%, 33.33% respectively) while their negative predictive values were similar. Conclusions E6/E7 mRNA detection has higher diagnostic values for the prediction of treatment failure compared with HPV‐DNA testing and p16/Ki67 immunocytochemistry, and as an outcome could be used as predictive indicator of CIN‐treatment status.