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The aim of this study was to calculate the validity parameters of the Digene Hybrid Capture 2 (HC2) high-risk human papillomavirus DNA test with and without cytology in the follow-up examinations after laser treatment of the transformation zone or large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN).We performed a standardized follow-up examination in 113 postlaser and 153 post-LLETZ patients in our colposcopy clinic. Routine cytology, HC2 tests, and colposcopically-guided cervical biopsies were performed and sensitivity, specificity, and positive and negative predictive values were calculated using the histological cervical biopsy result as the criterion standard.After a median follow-up time of 25.5 months, the overall posttreatment recurrence/persistence rate of CIN 2 or higher (CIN 2+) was 24% after laser and 12.4% after Post-LLETZ treatment. Hybrid Capture 2 alone had a sensitivity/NPV of 70/88% in post-laser and 70/93% in post-LLETZ patients. Cytology alone had a sensitivity/NPV for CIN 2+ of 48/84% in post-laser and 58/91% in post-LLETZ patients. Combined testing of HC2 with cytology had a sensitivity/NPV of 81/92% in postlaser and 88/95% in post-LLETZ patients.In this test of cure study, combined testing of cytology with HC2 resulted in a high sensitivity and NPV. Hybrid Capture 2 and cytology-negative women may safely return to routine recall. Cytology alone is not an adequate follow-up strategy in postlaser patients.