Expanding the upper age limit for cervical cancer screening: a protocol for a nationwide non-randomised intervention study

Abstract

Introduction: Cervical 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 analysis: This 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 dissemination: The 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 number: NCT04114968.

Keywords: cytopathology; epidemiology; gynaecology; preventive medicine; public health.

Conflict of interest statement

Competing interests: Roche sponsors the Cobas HPV-DNA test kits and CINtec Plus test kits for the study. According to the contract between Roche and the Department of Public Health Programmes, Randers Regional Hospital, Roche has commented on the protocol article, but had no influence on the scientific process and no editorial rights pertaining to this manuscript. The authors retained the right to submit the manuscript. MT, JB, JSJ and BA have participated in other studies with HPV test kits sponsored by Roche and self-sampling devices sponsored by Axlab. MT has received honoraria from Roche Diagnostics and AstraZeneca for lectures on HPV self-sampling and HPV triage-methods, respectively. AH has received lecture fees from AstraZeneca. All authors declare no conflicts of interest.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Map of the intervention and reference regions.

Figure 2

Clinical management of women attending screening at a GP. HPV other types than HPV16/18: 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. ≥ASC-US includes:atypical squamous cells of undetermined significance (ASC-US); low-grade squamous intraepithelial lesion (LSIL); atypical squamous cells cannot exclude HSIL (ASC-H); high-grade squamous intraepithelial lesion(HSIL); squamous cell carcinoma (SCC); atypical glandular cells (AGC); adenocarcinoma in situ (AIS); adenocarcinoma (ACC) and malignant tumour cells. GP, general practitioner; HPV, human papillomavirus;

Figure 3

Clinical management of women attending self-sampling. HPVother types than HPV16/18: 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. ≥ASC-US include: atypical squamous cells of undetermined significance (ASC-US); low-grade squamous intraepithelial lesion (LSIL); atypical squamous cellscannot exclude HSIL (ASC-H); high-grade squamous intraepithelial lesion (HSIL); squamous cell carcinoma (SCC); atypical glandular cells (AGC), adenocarcinomain situ (AIS); adenocarcinoma (ACC) and malignant tumour cells. ≥ASC-H include:ASC-H, HSIL, SCC, AGC, AIS, ACC and malignant tumour cells. *Compliance to follow-up among HPV positive self-samplers. **Follows the same algorithm as shown in figure 2 among women having repeating HPV testing after 3 months. GP, general practitioner; HPV, human papillomavirus.