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.

IntroductionCervical cancer screening ceases between the ages of 60 and 65 in most countries. Yet, a relatively high proportion of cervical cancers are diagnosed in women above the screening age. This study will evaluate if screening of women aged 65–69 years may result in increased detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared with women not invited to screening. Invited women may choose between general practitioner (GP)-based screening or cervico-vaginal self-sampling. Furthermore, the study will assess if self-sampling is superior to GP-based screening in reaching long-term unscreened women.Methods and analysisThis population-based non-randomised intervention study will include 10 000 women aged 65–69 years, with no record of a cervical cytology sample or screening invitation in the 5 years before inclusion. Women who have opted-out of the screening programme or have a record of hysterectomy or cervical amputation are excluded. Women residing in the Central Denmark Region (CDR) are allocated to the intervention group, while women residing in the remaining four Danish regions are allocated to the reference group. The intervention group is invited for human papillomavirus-based screening by attending routine screening at the GP or by requesting a self-sampling kit. The reference group receives standard care which is the opportunity to have a cervical cytology sample obtained at the GP or by a gynaecologist. The study started in April 2019 and will run over the next 4.5 years. The primary outcome will be the proportion of CIN2+ detected in the intervention and reference groups. In the intervention group, the proportion of long-term unscreened women attending GP-based screening or self-sampling will be compared.Ethics and disseminationThe study has been submitted to the Ethical Committee in the CDR which deemed that the study was not notifiable to the Committee and informed consent is therefore not required. The study is approved by the Danish Data Protection Regulation and the Danish Patient Safety Authority. Results will be disseminated in peer-reviewed journals.Trial registration numberNCT04114968.

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Background High-risk human papillomavirus (HPV) test is replacing cytology as the primary cervical cancer screening test due to superior sensitivity, but in most countries women ≥65 years have never had an HPV test despite they account for around 50% of cervical cancer deaths. We explored the effect of a catch-up HPV test among 65- to 69-year-old women without previous record of HPV-based screening. Methods and findings This population-based nonrandomized intervention study (quasi-experimental design) included Danish women aged 65 to 69 with no record of cervical cancer screening in the last ≥5.5 years and no HPV-exit test at age 60 to 64 at the time of study inclusion. Eligible women residing in the Central Denmark Region were invited for HPV screening either by attending clinician-based sampling or requesting a vaginal self-sampling kit (intervention group, n = 11,192). Women residing in the remaining four Danish regions received standard care which was the opportunity to have a cervical cytology collected for whatever reason (reference group, n = 33,387). Main outcome measures were detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) per 1,000 women eligible for the screening offer and the benefit–harm ratio of the intervention and standard practice measured as the number of colposcopies needed to detect one CIN2+ case. The minimum follow-up time was 13 months for all tested women (range: 13 to 25 months). In the intervention group, 6,965 (62.2%) were screened within 12 months from the date of study inclusion and 743 (2.2%) women had a cervical cytology collected in the reference group. The CIN2+ detection was significantly higher in the intervention group (3.9, 95% confidence interval (CI): [2.9, 5.3]; p < 0.001; n = 44/11,192) as compared to the reference group (0.3, 95% CI: [0.2, 0.6]; n = 11/33,387). For the benefit–harm ratio, 11.6 (95% CI: [8.5, 15.8]; p = 0.69; n = 511/44) colposcopies were performed to detect one CIN2+ in the intervention group as compared to 10.1 (95% CI: [5.4, 18.8]; n = 111/11) colposcopies in the reference group. The study design entails a risk of confounding due to the lack of randomization. Conclusions The higher CIN2+ detection per 1,000 eligible women in the intervention group supports that a catch-up HPV test could potentially improve cervical cancer prevention in older women. This study informs the current scientific debate as to whether women aged 65 and above should be offered a catch-up HPV test if they never had an HPV test. Trial registration ClinicalTrials.gov NCT04114968.

Objectives The strong association between atypical endometrial hyperplasia and endometrial carcinoma is well established, but data on the risk of atypical hyperplasia and carcinoma in Danish women with non-atypical endometrial hyperplasia are almost non-existent. This study aimed to investigate the prevalence of atypical hyperplasia and endometrial carcinoma diagnosed within 3 months of initial diagnosis (defined as concurrent disease) and the risk of atypical hyperplasia and carcinoma more than 3 months after initial diagnosis (classified as progressive disease) in Danish women initially diagnosed with non-atypical endometrial hyperplasia. Design This cohort study recruited 102 women diagnosed with non-atypical endometrial hyperplasia at Randers Regional Hospital in Randers, Denmark, between 2000 and 2015. Methods The endometrium was evaluated by transvaginal ultrasound examination and office mini-hysteroscopy with biopsies in all non-hysterectomized women. Data regarding subsequent hysterectomy or endometrial sampling were obtained from medical records and the Danish Pathology Registry (Patobank). Results A total of 15 women were diagnosed with atypical hyperplasia or carcinoma during follow-up. Concurrent atypical hyperplasia or carcinoma was seen in 2.9% (3/102), and among women who remained at risk for more than 3 months after initial diagnosis of non-atypical endometrial hyperplasia (n = 94), progression to atypical hyperplasia or carcinoma was seen in 13% (median follow-up 5.2 years, range 3.6 months to 15.1 years). Sixty-six percent of the women with progressive disease were diagnosed with atypical hyperplasia or carcinoma more than 1 year after initial diagnosis, but only two were diagnosed later than 5 years (5.2 and 9 years). Conclusions The risk of being diagnosed with atypical endometrial hyperplasia or endometrial carcinoma more than 5 years after an initial diagnosis of non-atypical endometrial hyperplasia seems to be low in Danish women. Specialized follow-up more than 5 years after diagnosis of non-atypical endometrial hyperplasia may not be warranted.