Public Health 225 (2023) 369e375

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Original Research

Factors associated with advanced-stage diagnosis of cervical cancer in

Estonia: a population-based study


A. Savrova a, * ~ mm c, K. Innos c
, J. Jaal b, O. No
a
North Estonia Medical Centre Foundation, Womens Clinic, J. Sütiste tee 19, 13419, Tallinn, Estonia
b
Institute of Clinical Medicine, University of Tartu, L, Puusepa 8, 50406, Tartu, Estonia
c
National Institute for Health Development, Department of Epidemiology and Biostatistics, Hiiu 42, 11619, Tallinn, Estonia

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: Cervical cancer (CC) remains a crucial public health issue in Estonia, with high incidence and
Received 5 July 2023 late diagnosis. The aim of this study was to examine time trends of stage-specific CC incidence in Estonia
Received in revised form and factors associated with advanced-stage diagnosis of CC.
7 October 2023
Study design: This was a nationwide population-based retrospective study.
Accepted 11 October 2023
Available online 20 November 2023
Methods: Data on CC cases diagnosed in Estonia in 2007e2018 were obtained from the Estonian Cancer
Registry, including tumour, nodes, metastases stage at diagnosis. Sociodemographic data were obtained
from the Population Registry. To estimate the risk of advanced-stage diagnosis (stages IIeIV vs stage I)
Keywords:
Cervical cancer
associated with sociodemographic factors, Poisson regression with robust variance was used to calculate
Screening univariate and multivariate prevalence ratios (PR) with 95% confidence intervals (CIs). Time trends of
Stage stage-specific CC incidence for 2005e2019 were examined with joinpoint analysis.
Stage-specific incidence Results: Incidence of stage I CC showed a significant decline of 4.9% per year since 2007, whereas no
Sociodemographic factors change was seen for other stages. Of the 2046 women diagnosed in 2007e2018, 1137 (55.6%) were
Population-based study diagnosed at an advanced stage; this proportion increased from 51% in 2007e2009 to 58% in 2015e2018
(P ¼ 0.004). Multivariate regression analysis showed that advanced-stage diagnosis was associated with
age (PR 2.16, 95% CI 1.87e2.49 for women aged 75 years compared with those aged 30e44 years),
educational level (PR 1.32, 95% CI 1.15e1.51 for women with basic/primary education compared to
university education) and marital status (PR 1.14, 95% CI 1.01e1.29 for single women compared to
married/cohabiting women). No associations were observed by region of residence or nationality.
Conclusions: To reduce CC mortality, it is crucial to improve prevention and early diagnosis of CC in Estonia
through human papillomavirus vaccination and effective and quality-assured screening particularly targeting
high-risk groups as well as encouraging symptom awareness and regular check-ups among older women.
© 2023 The Authors. Published by Elsevier Ltd on behalf of The Royal Society for Public Health. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction While Estonia is typically considered a high-income country,1 it still

Although cervical cancer (CC) is largely preventable through
vaccination against high-risk subtypes of human papillomavirus
(HPV) and population-based screening, the rates of CC are still high
in many places in the world, particularly in low-income countries.
Abbreviations: CC, Cervical cancer; HPV, Human papillomavirus; ECR, Estonian
Cancer Registry; SCC, Squamous cell carcinoma; AC, Adenocarcinoma; TNM,
tumour, nodes, metastases; ICD-O-3, 3rd Edition of International Classification of
Disease for Oncology; IARC, International Agency for Research on Cancer; PR,
Prevalence ratio; CI, Confidence intervals; DCO, death certificate only; MRI, Mag-
netic resonance imaging.
* Corresponding author. North Estonia Medical Centre Foundation J. Sütiste tee
19, Tallinn, 13419, Estonia.


E-mail address: aleksandra.savrova@regionaalhaigla.ee (A. Savrova).
has very high CC incidence and mortality rates, ranking second and
eighth in the European Union, respectively, according to the 2020
estimates.2 Furthermore, a shift in stage distribution at diagnosis
toward later detection has been observed,3 highlighting a critical
need to improve both prevention and early detection.
Organised national CC screening programme in Estonia has been
in place since 2006. Until 2021, the primary screening test was Pap
smear offered every 5 years to women aged 30e55 years with valid
health insurance. In 2021, Estonia switched to HPV NAT test as the
primary screening test, and the screening age group was extended
to include women aged 30e65 years, and people without health
insurance were included in the target group. As of 2021, screening
coverage in the target population stands at 51%. HPV self-sampling

https://doi.org/10.1016/j.puhe.2023.10.025
0033-3506/© 2023 The Authors. Published by Elsevier Ltd on behalf of The Royal Society for Public Health. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
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~mm et al. Public Health 225 (2023) 369e375

has also been gradually introduced as an additional option to emigration/immigration status. Sociodemographic data were cat-
participate in CC screening since 2021, significantly increasing egorised as follows: nationality (Estonian, non-Estonian or un-
screening uptake.4 known), educational level (university and higher education,
Another important method of CC prevention is the use of HPV secondary education plus vocational education, secondary educa-
vaccine.5 Long-term studies have shown that vaccination signifi- tion, basic or primary education or unknown), and marital status
cantly reduces the risk of invasive CC among 10- to 30-year-old (married or cohabiting, divorced, widowed, single or unknown).
females.6 Although HPV vaccination has been implemented for
teenage girls in Estonia since 2018, vaccination coverage remains
Statistical analysis
low at 57%.7
Recent analysis has shown that CC incidence in Estonia has
Overall annual CC incidence (1968e2019) was calculated using
started to decline since 2013.8 Yet, it is not known which stages
ECR data on CC cases as defined above according to ICD-O-3 as
have contributed to this decrease. Previous studies have shown an
numerator. For stage-specific analyses, only cases with a specific
association of sociodemographic factors, such as age, education and
TNM stage were included in the numerator. Annual stage-specific
marital status with CC risk9 and participation in preventive care.10
incidence was calculated for 2005e2019 as TNM stage informa-
The impact of sociodemographic factors on CC stage at presenta-
tion was not available for earlier periods. Overall annual CC mor-
tion has been shown elsewhere.11 In Estonia, place of residence was
tality (1985e2020) was calculated based on data obtained from the
found to be a strong predictor of advanced-stage diagnosis in breast
Estonian Causes of Death Registry with all deaths where the un-
cancer.12 In this context, it can be expected that sociodemographic
derlying cause of death was coded as CC (ICD-10 code C53) included
factors also impact CC stage at presentation, but these associations
in the numerator. Annual population denominator data were ob-
have not been investigated in Estonia.
tained from Statistics Estonia. Incidence and mortality rates were
The aim of this study was to examine time trends of stage-
standardised to world standard population.
specific CC incidence in Estonia and to investigate which patient
Joinpoint Regression Program (version 4.1.1.1) from the Sur-
and tumour characteristics are independently associated with
veillance Research Program of the US National Cancer Institute
advanced-stage CC diagnosis.
(http://surveillance.cancer.gov/joinpoint) was used to model inci-
dence and mortality rates to estimate annual percentage change
Methods
(APC) with 95% confidence intervals (CIs). Joinpoint regression
detects points of significant change (joinpoints) in the log linear
Data sources and definitions
slope of the trend. Permutation tests were used to assess the sta-
tistical significance of the APCs, where APC was significantly
Data on CC cases were obtained from the Estonian Cancer
different from zero at a ¼ 0.05.
Registry (ECR), which is a population-based cancer registry
Statistical software StataCorp LLC, 4905 Lakewy Drive, College
covering the whole country and has data since 1968. The ECR used
Station, Texas 77845-4512, USA14 was used to compare proportions
the third edition of the International Classification of Diseases for
between groups, using Chi-squared test, with a two-sided P-value
Oncology (ICD-O-3) to classify the topography and morphology of
of <0.05 considered to be statistically significant. To examine the
the tumours. The data included information on all invasive CC cases
association between independent variables and advanced stage at
(ICD-O-3 topography codes C53.0-C53.9) diagnosed in Estonia in
the time of diagnosis (outcome variable), we used univariate and
2007e2018, regardless of cancer sequence. The data collected from
multivariate Poisson regression models with robust variance to
the ECR included personal information and details about diagnosis,
calculate prevalence ratios (PRs) with 95%CIs. These models were
such as date of diagnosis, morphology of the tumour, age, stage at
constructed using generalised linear models with a Poisson family
diagnosis and region of residence.
and a log link function, which were incorporated into the analysis
Stage at diagnosis was classified according to the Union for In-
within Stata. The reason for selecting this method was that the odds
ternational Cancer Control tumour, nodes, metastases (TNM) clas-
ratio calculated with logistic regression tends to overestimate the
sification version 7. Early stage was defined as stage I and advanced
association between variables when the prevalence is high.15,16
stage as stages IIeIV. From stage distribution analysis, we excluded
Cases with unknown stage were excluded from regression
death certificate only cases (n ¼ 11) and those diagnosed at autopsy
modelling. Cases with unknown sociodemographic characteristics
(n ¼ 7). Histological type was defined as squamous cell carcinoma
were excluded from models that included the specific character-
(SCC), adenocarcinoma (AC) or other based on the International
istic. Variables selected for multivariate models were those
Agency for Research on Cancer classification, using ICD-O-3
showing significant association in univariate analysis or those of a
morphology codes:13 SCC (8050e8078, 8083e8084) and AC
priori interest: period of diagnosis, age at diagnosis, nationality,
(8140e8141, 8190e8211, 8230e8231, 8260e8265, 8310, 8380,
region of residence, education, marital status, and tumour
8382e8384, 8440e8490, 8570e8574, 8576). ‘Other/unspecified’
morphology.
morphology group included all other morphologies (including 30
The study protocol was approved by the Tallinn Medical
cases of adenosquamous tumours) as well as cases without
Research Ethics Committee (Decision no 2652, March 12, 2019).
microscopic verification. Age at diagnosis was grouped into five
categories: <30, 30e44, 45e59, 60e74 and 75 years. Period of
diagnosis was divided into three 4-year categories: 2007e2010, Results
2011e2014 and 2015e2018. Region of residence was grouped into
five categories: Northern, Western, Central, North-Eastern, and Incidence and mortality trends
Southern Estonia.
Information on sociodemographic factors (education, marital CC incidence in Estonia started to decrease from 2012 at a rate of
status, nationality) was collected from the Population Registry 4.1% per year after a lengthy period of increase (Fig. 1A). CC mor-
through data linkage using unique personal identification numbers tality has been declining since 1985 (APC -1.4). The decrease in
that have been in use in Estonia since 1992. The Population Registry incidence has been limited to stage I CC, which showed a decline of
is continuously updated and includes current information on 4.9% per year since 2007 (Fig. 1B). No changes have been apparent
Estonian citizens and residents, including data on their vital and in stages IIeIV CC incidence.
370
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Savrova, J. Jaal, O. No
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Fig. 1. Observed (dotted line) and modelled (solid line) age-standardised rates and annual percentage change (APC) for trends in (A) all-stage cervical cancer incidence (1968e2019)
and mortality (1985e2010); and (B) stage-specific cervical cancer incidence (2005e2019) in Estonia. In bold: the APC is significantly different from zero at alpha ¼ 0.05.
Stage at diagnosis
A total of 2064 CC cases were diagnosed in Estonia in
2007e2018. After the exclusion of death certification only (DCO)
and autopsy cases, 2046 cases were included in the analysis
(Table 1). The mean age of the patients was 54.4 years (range 22e95
years). Most of the women were Estonian, had secondary educa-
tion, were married/cohabiting, and lived in Northern Estonia
(including the capital city of Tallinn). In terms of tumour
morphology, 79.9% were categorised as SCC, 11.3% as AC, and 8.8%
had other/unspecified morphology.
Of 2046 cases, 1874 (91.6%) had proper staging according to the
TNM classification; 36.0% were diagnosed at an early stage (stage I)
and 55.6% at an advanced stage (stages IIeIV; Table 1). The pro-
portion of advanced-stage diagnosis increased over time and was
significantly higher among older women (71.5% and 66.9% in
women aged 75 years and 60e74 years, respectively), those with
lower educational level (62.1% among women with basic or primary
education), and unmarried women (61.6% among widowed
women). Table 2 presents the change in the proportion of
advanced-stage diagnosis over time by patient characteristics
among women with known stage. Overall, the proportion of
advanced-stage diagnosis increased by 8.3 percentage points from
55.7% in 2007e2010 to 64.0% in 2015e2018. There were significant
increases in the proportion of advanced stage between the first and
last periods in age group 45e59 (increase by 13.7%, P ¼ 0.004),
among Estonians (10.5%, P ¼ 0.002), among women with secondary
education (14.2%, P ¼ 0.002), among divorced (10.7, P ¼ 0.046) and
single women (15.2%, P ¼ 0.025), among women living in Southern
Estonia (12.6%, P ¼ 0.033) and among SCC cases (7.8%, P ¼ 0.015).
In univariate Poisson regression analysis, advanced-stage CC
diagnosis was associated with period of diagnosis, age, education,
marital status, and tumour morphology (Table 3). After adjusting
for all other variables in multivariate analysis, a 14% increase in
advanced-stage diagnosis was observed over the study period (PR
1.14, 95% CI 1.04e1.25). The risk of advanced-stage diagnosis
371
Public Health 225 (2023) 369e375
increased with age, being over two times higher in the oldest age
group compared with women aged 30e44 years (PR 2.16, 95% CI
1.87e2.49). A clear relationship between advanced-stage CC and
education was observed: women with the lowest level of education
were 30% more likely to be diagnosed with CC at an advanced stage
than those with university education (PR 1.32, CI 95% 1.15e1.51).
Single women were slightly more likely to have advanced CC at
diagnosis compared with married women (PR 1.14, CI 95%
1.01e1.29). While there was no difference in stage at diagnosis
between SCC and AC, cases with other/unspecified morphology
were more likely to be diagnosed at an advanced stage. No asso-
ciations were observed in multivariate analysis by region of resi-
dence or nationality.
Discussion
This population-based study revealed important insights into the
incidence and characteristics of CC cases in Estonia. The findings
show a 4% annual decline in CC incidence since 2012, following a 30-
year period of increase. CC mortality has been decreasing since 1985.
The decline in incidence was limited to stage I CC, starting imme-
diately after the introduction of screening. However, there was no
change in the incidence for stages II and higher. As a result, the
proportion of advanced stage CC increased by 8 percentage points
over the study period. In multivariate analysis, advanced-stage CC
risk increased over time and was significantly higher among women
who were older, with lower educational level and single.
Organised Pap smear-based CC screening in Estonia suffered
from several limitations, including low upper age limit and exclu-
sion of women without health insurance. Since the beginning of the
programme, screening participation rates have been below 50%,17
and many Pap smears have been administered outside the organ-
ised programme. In addition, there has been no regular quality
assurance. The smears were analysed at many laboratories, some of
them with low test volume. A recent study revealed that many
cytology tests conducted just before CC diagnosis failed to identify
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Table 1
Characteristics of women diagnosed with cervical cancer by stage at diagnosis, Estonia 2007e2018.

Variable Total Stage at diagnosis P-valuea

Early Advanced Unknown

No. % No. Row% No. Row% No. Row%

Total 2046 100 737 36.0 1137 55.6 172 8.4

Period of diagnosis 0.004
2007e2010 752 36.8 305 40.6 384 51.1 63 8.4
2011e2014 725 35.4 245 33.8 421 58.1 59 8.1
2015e2018 569 27.8 187 32.9 332 58.3 50 8.8
Age at diagnosis <0.001
<30 65 3.2 40 61.5 17 26.2 8 12.3
30e44 482 23.6 276 57.3 181 37.6 25 5.2
45e59 734 35.9 269 36.6 415 56.5 50 6.8
60e74 502 24.5 118 23.5 336 66.9 48 9.6
75 263 12.9 34 12.9 188 71.5 41 15.6
Nationality 0.289
Estonian 1402 68.5 514 36.7 764 54.5 124 8.8
Non-Estonian 630 30.8 220 34.9 363 57.6 47 7.5
Unknown 14 0.7 3 21.4 10 71.4 1 7.1
Region of residence 0.259
North 786 38.4 288 36.6 463 58.9 35 4.5
Central 247 12.1 87 35.2 127 51.4 33 13.4
North-East 243 11.9 80 32.9 142 58.4 21 8.6
South 489 23.9 192 39.3 250 51.1 47 9.6
West 281 13.7 90 32.0 155 55.2 36 12.8
Education <0.001
Basic and Primary 425 20.8 114 26.8 264 62.1 47 11.1
Secondary 787 38.5 284 36.1 428 54.4 75 9.5
Secondary vocational 366 17.9 148 40.4 196 53.6 22 6.0
University and higher 326 15.9 158 48.5 150 46.0 18 5.5
Unknown 142 6.9 33 23.2 99 69.7 10 7.0
Marital status <0.001
Married/cohabiting 619 30.3 262 42.3 315 50.9 42 6.8
Divorced 577 28.2 203 35.2 335 58.1 39 6.8
Widow 422 20.6 107 25.4 260 61.6 55 13.0
Single 362 17.7 144 39.8 189 52.2 29 8.0
Unknown 66 3.2 21 31.8 38 57.6 7 10.6
Tumour morphology 0.001
SCC 1635 79.9 604 36.9 907 55.5 124 7.6
AC 231 11.3 97 42.0 123 53.2 11 4.8
Other 180 8.8 36 20.0 107 59.4 37 20.6

AC, adenocarcinoma; SCC, squamous cell carcinoma.

Note: row percentages may not equal 100% due to rounding.
a
Chi-squared test comparing proportions of early and advanced stage.

any abnormalities,18 particularly tests that were analysed at local
laboratories.18,19 Previous findings have shown that women who
live in Estonian regions other than the Northern capital region were
at a higher risk of CC, which might also be related to Pap smear
quality.20 As the screening registry started only in 2015, no routine
data have been available to support the quality assurance of the
screening programme.
In previous studies elsewhere, the effect of screening on CC
stage has not been consistent. In Italy, the implementation of cer-
vical screening resulted in larger reductions in advanced stages of
CC rather than microinvasive cases.21 Conversely, patients who
underwent more frequent screening were more likely to be diag-
nosed at an early stage in Scotland.22 In the United States and newly
independent states of former Soviet Union, despite a decline in
early-stage CC rates, there has been an increasing trend of distant
stage CC.23,24 In Lithuania, a shift towards more advanced stages of
CC was observed,25 mirroring the trends seen in our study.
Our findings that the incidence decline of CC has been limited to
stage I disease suggest that the screening programme has been
effective in preventing CC cases in women who would have been
diagnosed at an early stage even without screening. At the same
time, there might be a group of women who do not participate in
screening programmes regularly and only seek medical attention
when they experience severe symptoms at advanced stages. This
372
suggestion is further supported by our finding that women with
lower socio-economic status, as measured by their educational
level, were more likely to be diagnosed at an advanced stage. Pre-
vious research from Estonia has shown that women with lower
education were less likely to have had a Pap smear during their
lifetime,10 and education was related with higher risk of CC even
after adjusting for screening participation.9 Possible reasons for the
higher risk among women with low socio-economic status include
early sexual activity, pregnancies that may modify the carcinogenic
potential of HPV infection, and limited access to healthcare ser-
vices.26 It is important to note that healthcare access in Estonia is
dependent on one's health insurance coverage. The main categories
of people covered by health insurance include employed and
retired persons, children and pregnant women. Unemployed peo-
ple are covered for a limited period. Up to 2021, free cancer
screening programmes were not available for persons with no in-
surance coverage. Thus, the associations seen in this study between
low socio-economic status and advanced-stage disease may be
mediated by limited access to health care, including screening.
Interruptions in health insurance coverage were associated with a
25% increase in CC risk.9
Older women were at a higher risk of being diagnosed with
advanced-stage CC in our study. It has been estimated that
approximately 50% of cases diagnosed at an advanced stage were
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Table 2
Proportion of cervical cancer cases with advanced stage at diagnosis, Estonia 2007e2018.

Variable Advanced-stage diagnosis (%) Change from first to last period

2007e2010 2011e2014 2015e2018 P-valuea

b
Total 55.7 63.2 64.0 8.3 0.148
Age at diagnosis
<30 26.1 40.0 21.4 4.7 0.749
30e44 34.7 40.0 45.5 10.8 0.058
45e59 55.2 60.7 68.9 13.7 0.004
60e74 70.6 79.0 70.5 0.1 0.992
75 83.8 87.3 83.1 0.7 0.914
Nationality
Estonian 53.6 63.1 64.1 10.5 0.002
Other 59.7 63.6 63.7 4.0 0.441
Region of residence
North 57.6 64.0 64.6 7.0 0.118
Central 56.0 59.5 63.6 7.6 0.381
North-East 61.5 67.4 61.0 0.5 0.953
South 50.0 58.8 62.6 12.6 0.033
West 55.7 67.9 67.1 11.4 0.135
Education
Basic and primary 67.4 74.2 67.7 0.3 0.957
Secondary 52.5 63.0 66.7 14.2 0.002
Secondary vocational 53.3 55.7 62.6 9.3 0.179
University and higher 41.5 56.1 48.4 6.9 0.325
Marital status
Married/cohabiting 49.5 59.0 55.9 6.4 0.217
Divorced 58.3 61.3 69.0 10.7 0.046
Widow 64.7 74.4 76.5 11.8 0.060
Single 47.2 60.3 62.4 15.2 0.025
Tumour morphology
SCC 56.2 61.3 64.0 7.8 0.015
AC 41.4 66.3 54.3 12.9 0.146
Other 67.4 78.0 79.6 12.2 0.185

AC, adenocarcinoma; SCC, squamous cell carcinoma.

Note: row percentages may not equal 100% due to rounding.
a
Chi-squared test comparing first and last period.
b
Unknown stage excluded.

among non-attenders of the screening programme or women
beyond the recommended screening ages.27 Older age has been
previously shown to be associated with longer interval between
first contact with healthcare providers and cancer diagnosis.28 This
may be also because of the impaired diagnostic work-up of Pap
smears in postmenopausal age due to cervical epithelium atrophy
and retraction of the squamocolumnar junction. In addition to
older women being excluded from the nationwide screening pro-
gramme, their irregular attendance to gynaecologists due to being
non-sexually active and perceiving it as unnecessary could
contribute to inadequate follow-up.
Furthermore, the study found that single patients were slightly
more likely to have advanced CC compared to married patients,
which is consistent with previous research.29,30 In a recent meta-
analysis, marriage was positively associated with early diagnosis
and better survival.29 It is possible that the partner may recognise
the signs of the disease and encourage the woman to get medical
treatment, as CC often does not have any symptoms in its early
stages. Compared to single, divorced, or widowed women, married
women may have a more favourable financial situation and mate-
rial support.31 A recent study showed that married women were
more likely to have had a Pap smear in the last 3 years.32
Consistently with previous findings,23 morphology was not
found to be associated with advanced-stage presentation in our
study, and there was a significant rise in the proportion of
advanced-stage CC over time among both SCC and AC cases. In
recent years, there has been an increase in the incidence of cervical
adenocarcinoma in Western countries.33,34 Women with adeno-
carcinoma were also found to be more likely to have had a negative
screening test before cancer diagnosis (72% vs 45%, P < 0.001).35 But
there is hope that if screening coverage is adequate, the incidence
of cervical adenocarcinoma may decrease in the future, as it was
demonstrated in England in late 1990s.34
Undoubtedly, an increase in screening coverage in the target
population can decrease CC incidence, including advanced-stage
CC. Previous studies have shown that lack of screening is associ-
ated with advanced-stage CC diagnosis.36 With the shift to the HPV-
based screening programme, it is expected that the first round of
HPV screening will detect prevalent cases of invasive cancers and
precursor lesions.37,38 Further outcomes will depend on the man-
agement of women with persistent HPV infection, cytological ab-
normalities and precancerous lesions. Effectiveness of follow-up
procedures and treatments, including the quality of colposcopy,
will be crucial.39
However, the results also emphasised the importance of timely
detection and CC diagnosis in those who do not belong to the
screening age group through ensuring equitable access to health
care and minimal delays in the healthcare system. The average
delay in diagnosing CC has been shown to range from 2.9 to 10.5
months.40 While Estonia is one of Europe's smaller countries, un-
equal access to healthcare services may be influenced by the
shortage of family doctors and the patients' length of journey to
healthcare providers. One of the reasons cited by women for not
undergoing screening is the extended waiting time for appoint-
ments and the inconvenience of travelling to distant clinics.41
The main strength of the study was that it was a large
population-based study, using high-quality data from national
registries, and the availability of TNM stage data. One of the limi-
tations of the study was the inability to correct for hysterectomies
due to the lack of population-based data that could be used to

373
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Table 3 Future efforts in Estonia should also focus on promoting HPV

Prevalence ratio (PR) of advanced-stage diagnosis among women with cervical vaccination. Long-term and continuous surveillance and evaluation
cancer, Estonia 2007e2018.
are necessary to monitor the impact of interventions and guide
Variable Univariate Multivariatea further improvements.
PR 95 % CI PR CI 95 %

Period of diagnosis Author statements

2007e2010 ref ref
2011e2014 1.13 1.04e1.24 1.13 1.03e1.24 Acknowledgements
2015e2018 1.14 1.05e1.26 1.14 1.04e1.25
Age at diagnosis
The authors would like to thank Dr Margit Ma €gi from the
<30 0.75 0.50e1.14 0.67 0.42e1.05
30e44 ref ref Estonian Cancer Registry for providing the data and Dr Alisson
45e59 1.53 1.35e1.74 1.55 1.35e1.77 Curry and Nicolay Karaliou for their valuable advice on earlier
60e74 1.87 1.65e2.12 1.89 1.65e2.16 drafts of the manuscript.
75 2.14 1.88e2.43 2.16 1.87e2.49
Nationality
Estonian ref ref Ethical approval
Other 1.04 0.96e1.13 1.04 0.95e1.14
Region of residence The study protocol was approved by the Tallinn Medical
North ref ref
Research Ethics Committee (Decision no 2652, March 12, 2019).
Central 0.96 0.85e1.09 0.94 0.82e1.07
North-East 1.04 0.93e1.16 1.01 0.89e1.14
South 0.92 0.83e1.01 0.92 0.83e1.02 Funding
West 1.03 0.92e1.15 1.01 0.90e1.13
Education
This study was supported by Estonian Research Council (Grant
Basic and primary 1.43 1.26e1.64 1.32 1.15e1.51
Secondary 1.23 1.08e1.40 1.19 1.05e1.35 No. PRG722).
Secondary vocational 1.17 1.01e1.36 1.12 0.96e1.29
University and higher ref ref Competing interests
Marital status
Married/cohabiting ref ref
Divorced 1.14 1.03e1.26 1.05 0.95e1.15 All authors declare no conflicts of interest associated with this
Widow 1.30 1.18e1.43 0.97 0.87e1.08 study.
Single 1.04 0.92e1.17 1.14 1.01e1.29
Tumour morphology
Data availability statement
SCC ref ref
AC 0.93 0.82e1.05 0.94 0.84e1.06
Other 1.25 1.12e1.38 1.15 1.04e1.29 Data will be made available on request.
AC, adenocarcinoma; ref, reference category; SCC, squamous cell carcinoma.
Statistically significant findings in bold. Author contributions
a
Simultaneously adjusted for all variables in the table.
All authors participated in the revision process and have
approved the submitted version. A.S.
contributed to con-
obtain correction factors. This may have caused underestimation of
ceptualisation, methodology, formal analysis, data curation, and
incidence and mortality rates, particularly in older age groups.
writing e original draft and editing. O.N. contributed to formal
Hysterectomy rates in Estonia have been declining.42 However, in
analysis and writing e reviewing and editing. K.I. contributed to
this paper, we have only analysed age-adjusted CC trends. Cor-
conceptualisation, methodology, data curation, formal analysis,
recting for hysterectomies did not change the age-adjusted trend of
writing e reviewing and editing, and supervision. J.J. contributed to
CC incidence in Finland.43
reviewing and editing the article.
As another limitation, we were not able to consider individual
screening history and determine cases diagnosed through CC
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