This study was designed as a nationwide cross-sectional study in Denmark based on registry data. Denmark has a total of 5.6 million inhabitants, with 1.5 million women in the target population for cervical cancer screening [18]. Systematic cervical cancer screening was introduced in the 1960s in some counties and non-systematically implemented in the rest of the country until nationwide coverage was achieved in 2007 [19].
The policy of cervical cancer screening is defined nationally and administered by Denmark’s five regions. Every third year, women ages 23 to 49 years are invited for cervical cancer screening while women ages 50 to 64 years are invited every fifth year. A woman in the target population receives a personal invitation 3 or 5 years after her last cervical cytology unless she has declined to be a part of the program. The invitation advises the woman to book an appointment at her GP for a pelvic examination. When the cytology has been taken by the GP it will be mailed to the local department of pathology for analysis. If a cervical cytology is not obtained, a reminder is sent out 3 months (90 days) after the primary invitation and potentially a second reminder after 6 months (180 days) [18]. If no cytology is taken within 3 or 5 years after the last invitation, a new invitation is mailed. Danish guidelines do not recommend cervical cancer screening during pregnancy, but testing can be resumed 8–12 weeks postpartum [20]. Immigrants receive an invitation for cervical cancer screening when they obtain a Danish civil registration number (CRN). Outside the organised screening program, a GP or a gynaecologist can obtain an opportunistic cervical cytology at any time. The local pathology department analyses opportunistic as well as invitational cervical cytologies.
If a woman has an abnormal or inadequate cervical cytology result, she will be enrolled in a surveillance program [20]. In the surveillance program, women are tested more frequently than recommended in the screening program and therefore receive no invitation for screening. Duration and intensity of the surveillance program depend on the severity of the identified abnormality. In the Danish program, both invitational and opportunistic cervical cytologies are performed free of charge [20].
Study population
Our study population included women ages 23–49 years who were registered in the Danish National Pathology Data Bank (DPB) with a cervical cytology between 1 January 2010 and 30 June 2013 (3.5 years). Women aged 50–64 years were not included in this study because of a different screening interval as compared to women aged 23–49 years. Study inclusion was based on a first cervical cytology registered after 1 January 2010 (the index cervical cytology). Exclusion criteria were as follows (Fig. 1): abnormal cervical cytology finding prior to the index cervical cytology, indicating that the index cervical cytology could be part of a surveillance program (see Appendix 1 for used codes); an inadequate cervical cytology prior to the index cervical cytology, indicating that the index cervical cytology was taken, for example, because of a lack of cytological material for diagnostic assessment; being unsubscribed to the systematic screening program and therefore not receiving any invitations; and/or being registered with an index cytology but having no former invitation or cervical cytology.
Data sources
Cervical cytology
We collected data on cervical cytology from the DPB. This database use the Systematised Nomenclature of Medicine (SNOMED) to store detailed records of all pathology specimens, including cervical cytology analysed in Denmark since 1997 [21]. For cervical cytologies, the Bethesda classification has been recommended since 2010 [22]. Before 2010, the most used classification system for cervical cytologies was a modified World Health Organization classification [23], which can easily be translated into the Bethesda classification (see Appendix 1).
In DPB, we identified cervical cytologies using the SNOMED codes of cervix uteri: T8X3* [18]. For each cervical cytology, we identified the date of the last invitation, date of sample acquisition, and date of the latest cytology taken before the index cytology. Data on cytological diagnosis were retrieved using the SNOMED codes according to the Bethesda classification, as follows: normal cells; atypical squamous cells of undetermined significance (ASCUS); atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H); atypical glandular cells (AGC); low-grade squamous intraepithelial lesion (LSIL); HSIL; carcinoma in situ and adenocarcinoma in situ (AIS); carcinoma (including squamous carcinoma and adenocarcinoma); inadequate cervical cytology (not suitable for diagnosis); and others, e.g., necrosis (Appendix 1).
Sociodemography
Data on sociodemographic characteristics of women in the study population by the end of 2012 were obtained from The Danish Integrated Database for Labour Market Research (IDA) [24], which is annually updated for all Danish citizens. Educational level was classified according to UNESCO classification as low (≤10 years), middle (11–15 years), or higher education (>15 years). Occupation was classified as employed; self-employed and chief executive; unemployed or receiving supplementary benefits other than social welfare; retired; social welfare recipient; or other. Marital status was classified as married or living in a registered partnership, cohabitating, or single. Ethnicity was divided into Danish, immigrants from western countries, or immigrants from non-western countries, according to Statistics Denmark’s definition of developed countries [25]. Residence region was classified as North Denmark, Central Denmark, Region of Southern Denmark, Capital Region of Denmark, or Region Sealand. Each woman’s age at the date of the index cervical cytology was calculated by subtracting the woman’s date of birth from the date of the index cytology. Age was categorised corresponding to previous studies as 23–28 years, 29–34 years, 35–42 years, or 43–49 years [17, 26].
Data handling
Every Danish citizen has a unique 10-digit CRN including the date of birth and four additional random digits [27]. Every contact with the health care system and all information on sociodemographic factors are registered through this CRN [27], which allowed us to link data on cervical cytology from DPB to data on sociodemography from the IDA database.
Categorisation of cervical cytology
As no registry data are available to distinguish the invitational cytologies from opportunistic cytologies, the cervical cytologies were categorised into three groups according to the time span between the date of the index cervical cytology and either the 1) date of the last invitation or 2) date of last cervical cytology, whatever was closest to the index cervical cytology. Categorisation was done as follows: A woman was categorised as being ‘screened after invitation’ if her index cervical cytology was registered within ≤270 days (9 months) after her latest invitation. The group of women who underwent opportunistic testing was divided into routine or sporadic testing. Thus, we defined a woman as undergoing ‘routine opportunistic testing’ if one of two conditions was present: the index cervical cytology was taken 9 months to 3 years (271 days to 1080 days) after the woman’s latest invitation (extended screening interval); or the index cervical cytology was performed 2.5 to 3 years (901–1080 days) after the woman’s latest cervical cytology, which is slightly before an invitation would have been sent. A woman with no invitation but an index cervical cytology taken less than 2.5 years after her latest cervical cytology was defined as having undergone ‘sporadic opportunistic testing’. This latter type of cervical cytology is taken at a shorter screening interval than recommended.
Statistics
Cervical cytology diagnoses
Prevalence proportion differences (PPDs) and prevalence proportion ratios (PPRs) with 95 % confidence intervals (CIs) were used to explore differences in the distribution of cytological diagnoses between women undergoing routine opportunistic testing and women screened after invitation, and between women having sporadic opportunistic testing and women being screened after invitation. Further, the analyses were stratified by age: 23–28 years, 29–34 years, 35–42 years and 43–49 years.
In a sensitivity analysis, we explored the impact of giving the women a longer time frame to respond to the invitation. Thus, we used ≤365 days as a cut-off value to differentiate between women screened after invitation and women undergoing opportunistic testing, which is in accordance with the definition in the Danish quality database for cervical cancer screening [18].
Sociodemography
Sociodemographic characteristics were reported for each of the three cervical cytology groups using proportions and chi-square tests.
We used a multinomial logistic regression model to estimate odds ratios (ORs) with 95 % CIs for the associations between sociodemography and routine opportunistic testing or sporadic opportunistic testing. Women being screened after invitation served as the reference group. Unadjusted analyses were performed with each independent variable followed by a multivariate model adjusting for all independent variables. Independent variables included age groups, residence region, ethnicity, marital status, occupation, and education. Identification of covariates was based on a literature review [26, 28, 29]. Initially, to check for multicollinearity between independent variables, the mean variance inflation factor (VIF) was calculated. Values above 10 indicate multicollinearity [30].
All statistical analyses were conducted using STATA 13.0.
Ethics
The study was approved by the Danish Data Protection Agency (j.no. 2007-58-0010). According to Danish Legislation and the Central Denmark Region committees on biomedical research ethics, the study did not need ethics approval because it was based solely on registry data.