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Objective To compare the proportion of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in cervical biopsies with that in large loop excision of the transformation zone (LLETZ) specimens in women aged ≥45 years with transformation zone type 3 (TZ3). Design Multicentre cross‐sectional study. Setting Three colposcopy clinics in the Central Denmark Region. Population Women aged ≥45 years referred to colposcopy as a result of a positive human papillomavirus (HPV) test and/or abnormal cytology and with TZ3 at colposcopy. Methods Women had multiple biopsies taken and an LLETZ was performed. Main outcome measures Histologically confirmed CIN2+ in biopsies compared with that in LLETZ specimens. Results Of 166 eligible women at colposcopy, 102 women with paired data from biopsies and LLETZ specimens were included for final analysis. The median age was 67.7 years (IQR 62.6–70.4 years), and most were postmenopausal (94.1%) and had undergone HPV‐based screening (81.3%). The CIN2+ detection rate was significantly higher in LLETZ specimens than in biopsies (32.4% vs 14.7%, difference 17.7%, 95% CI 6.3–29.0%), resulting in more than half of CIN2+ cases being missed in biopsies (54.5%, 95% CI 36.4–71.9%). The overall agreement between biopsies and LLETZ was 82.4% (95% CI 73.6–89.2%). Conclusions CIN2+ detection is underestimated in women aged ≥45 years with TZ3 if detection relies on the results of biopsies alone. To reduce the risk of underdiagnosis and overtreatment, future studies should explore the use of new biomarkers for risk stratification to improve discrimination between women at increased risk of CIN2+ who need to undergo LLETZ and women who may undergo follow‐up.

Cervical intraepithelial neoplasia grade 2 (CIN 2) is an equivocal diagnosis with high interobserver variation. Owing to high regression rates of 50%, many countries recommend active surveillance of CIN 2, especially in women younger than age 25-30 years, where regression rates are even higher (ie, 60%). Additionally, excisional treatment is associated with increased risk of reproductive harm, particularly preterm birth. Active surveillance typically consists of semi-annual follow-up visits for up to 2 years, including colposcopy and either cytology, testing for human papillomavirus, or both. Excisional treatment is recommended for progression or persistent disease after 2 years. Because active surveillance in younger women is relatively new, knowledge on subsequent risk of cervical cancer is limited. Considering human papillomavirus latency, women undergoing active surveillance might be at higher risk of cervical cancer than women undergoing excisional treatment. Furthermore, there are