In the follow-up of treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions, cer-vical cytology has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing showed high sensitivity and lower specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) seems to be an indicator of viral integration and it allows the identification of severe lesions. Our objective was to assess the clinical utility of E6/E7 mRNA determination in the follow-up of patients treated for HSIL/CIN. A retrospective obser-vational study including 407 patients treated for HSIL/CIN was performed. The recurrence rate and the validity of E6/E7 mRNA testing were evaluated. The recurrence rate of high-grade lesions was 1.7%. The sensitivity of the test was 88% in the first clinical revision and 100% in the second and third revisions. Specificity was 91% in the first revision, 92% in the second revision, and 85% in the third revision. The positive predictive value was 18% in the first medical revision, 10% in the second and 14% in the third. The negative predictive value was 100% in all follow-up visits. In conclusion, the E6/E7 mRNA test seems to be effective in ruling out recurrence after treatment for HSIL/CIN lesions.