Persistence of human papillomavirus infection after therapeutic conization for CIN 3: Is it an alarm for disease recurrence?

Objective. The aims of this study were (1) to examine whether HPV DNA is persistently detected in the cervix after therapeutic conization for CIN 3 and (2) to explore whether a patient with persistence of HPV infection is at risk of developing recurrent disease. Methods. Of 74 patients referred with CIN 3, 58 who were tested for HPV DNA in the pretreatment cervical lesions were enrolled in the study. After standard therapeutic conization, patients were followed prospectively at the outpatient clinic. Our follow-up protocol was to follow patients without therapeutic intervention as long as they developed no recurrence or recurrence of CIN 1 or 2, while patients who experienced recurrence of CIN 3 were recommended for reconization or hysterectomy. The polymerase chain reaction for detecting HPV DNA was performed using fresh cell samples from the cervix. Results. In 56 of 58 patients (96.6%), HPV DNAs were detected in their primary cervical lesions prior to conization. With regard to the distribution of HPV types, HPV type 16 family (types 16, 31, and 35) was identified in 28 cases (50.0%), type 18 family (types 18, 33 and 58) in 15 (26.8%), and type X in 18 (32.1%). Up to August 1999, all of the 58 patients have been followed with a mean follow-up period of 31.8 months (range: 12 to 73 months). After treatment, HPV DNA was persistently detected in 11 (19.6%) but negative in 45 (80.4%) of 56 HPV DNA-positive patients. HPV DNA was not detected in both HPV DNA-negative patients. Five of 11 persistently HPV DNA-positive patients (45.5%) developed CIN recurrence, while none of 45 persistently HPV DNA-negative patients did. Thus, there was a significant difference between the recurrence rates of these two groups (P < 0.0001). Both patients who were initially HPV DNA-negative developed no recurrence. Accordingly, the overall recurrence following conservative treatment for CIN 3 was 5 of 58 patients (8.6%). Conclusions. Patients with persistent HPV infection after conization for CIN 3 should be especially closely followed because they are at increased risk of developing disease recurrence. (C) 2000, Academic Press.