Prediction of recurrence after treatment for high‐grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation

Objectives The aim of this study was to examine the accuracy of the presence of high‐risk human papillomavirus (HR‐HPV) DNA (HR‐HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high‐grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow‐up cytology and the marginal status of the excised tissue. Design Prospective follow‐up study. Setting Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven. Population Seventy‐two women treated with conisation for CIN2 or CIN3. Methods Women were followed by HR‐HPV DNA test (Hybrid Capture II test of Digene®) every 3 to 6 months. The same vial was used for cytology and the HR‐HPV DNA test (SurePath™). All women were further followed by colposcopy and cytology for 24 months at 6‐month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy‐directed biopsy occurring within 24 months after treatment. HR‐HPV status was correlated with recurrent or residual CIN2+. Main outcome measures Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR‐HPV testing, marginal status and follow‐up cytology. HR‐HPV status was also correlated with section margins postconisation and with the first cervical smear. Results In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 ± 9.6 versus 39.8 ± 12.2 years, P= 0.007). All six women with recurrence were HR‐HPV positive, four had a positive follow‐up smear (≥atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR‐HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR‐HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR‐HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow‐up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status. Conclusion Persistence or clearance of HR‐HPV DNA is an early valid prognostic marker of failure or c