Cervical intraepithelial neoplasia grade 1 and long-term risk of progression and treatment

Cervical intraepithelial neoplasia grade 1 (CIN1) is often managed by active surveillance, as the risk of progression to high grade lesions is reported to be low, but long-term data is sparse. To inform management of CIN1, we estimated risk of progression and occurrence of treatment in women attending a cervical cancer screening program.

We used nationwide, registry data on all women aged 25-69 years attending the Norwegian Cervical Cancer Screening Program in 2002-2019. The eligible source population was women with at least one cytology registration (n = 1,771,876). Women with a histologically confirmed, first CIN1 diagnosis were included (n = 26,130) and followed for detection of CIN2+, defined as histologically confirmed CIN2, CIN3, adenocarcinoma in situ (AIS), or cervical cancer. CIN3+ was defined as CIN3, AIS, or cervical cancer. Treatment included both excision and ablation.

Overall, the cumulative incidence of CIN2+ increased to 9.5% (95% confidence interval (CI), 8.8 to 9.5) during the first year and to 19.0% (95% CI, 18.4-19.5) during the first five years. For women with high-grade cytology, 5-year cumulative incidence reached 26.0% (95% CI, 25.0-27.0), whereas for women with normal or low-grade cytology, but HPV16 and/or HPV18 positive status, the corresponding estimate was 25.0% (95% CI, 23.3-26.8). Other high-risk HPV genotypes and HPV negative status were associated with lower risks (5-year cumulative incidence 15.5% (95% CI, 14.5-16.6) and 8.2% (95% CI, 7.1-9.5), respectively). Detection of CIN3+ was substantial (cumulative incidence 5.7% (95% CI, 5.4-6.0) and 12.7% (95% CI, 12.2-13.1) after 1 and 5 years, respectively), and overall, cumulative incidence of treatment was 15.2% (95% CI, 14.7-15.7) after 5 years, following similar patterns as observed for CIN2+.

A differentiation of follow-up guidelines by index cytology and HPV16/18 status for women diagnosed with CIN1, might be warranted.