Risk of recurrent disease following conization of cervical intraepithelial neoplasia grade 3 according to post-conization HPV status and surgical margins.

To examine the absolute risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) following conization according to post-conization HPV status and surgical margins. A total of 11,006 women with CIN3 on the cone were followed for up to 14 years using nationwide registries. We estimated absolute risks of recurrent CIN2+ and sensitivity and specificity of HPV testing and margin status in predicting CIN2+ 4 years after conization. Altogether, 2537 women were HPV positive and 8469 were HPV negative. During follow-up, 306 and 140 women were diagnosed with CIN2+ among HPV positive and negative women, respectively. HPV positive women had higher absolute risk of CIN2+ compared to HPV negative women. Specifically, the 8-year absolute risk of CIN2+ was 12.5% (95% CI: 11.2-13.9) for HPV positive women and 1.8% (95%CI: 1.5-2.1) for HPV negative women. Among HPV negative women, the 8-year absolute risk was 2.7% (95%CI: 2.1-3.5) and 1.3% (95%CI: 1.0-1.7) for women with positive and negative margins, respectively. The same pattern was seen among HPV positive women. Combined testing with HPV and margins had a higher sensitivity but lower specificity than HPV testing alone. Our results add knowledge on long-term risk assessment of women treated with conization as taking both HPV and margin status into account added further stratification of the risk of recurrent disease compared to HPV status alone. Additionally, combined testing with HPV and margin status had higher sensitivity than HPV testing alone, which is important in high-risk populations, however, the specificity was lower.

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Declaration of Competing Interest SKK has received lecture fees from Merck and research grant through her institution from Merck