Background
Cervical cancer is the fourth most frequently diagnosed cancer, and the fourth leading cause of cancer deaths in women. According to the Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN), approximately 570,000 cases and 311,000 deaths of cervical cancer were estimated to have occurred in 2018 worldwide [
1]. Without significant intervention, the global burden of cervical cancer is expected to increase to nearly 700,000 cases and 400,000 deaths by 2030, representing a 21% and 27% increase in the number of cases and deaths, respectively [
2].
Persistent infection with high-risk types of human papillomavirus (hrHPV) is a necessary cause of cervical cancer [
3,
4]. Compelling evidence confirmed that HPV vaccination programs for the most common hrHPV would prevent approximately 87% of cervical cancer cases worldwide [
5]. Since HPV vaccination was licensed in 2006, approximately 80 countries and territories implemented national HPV vaccination programs, covering more than 100 million women [
6]. In 2018, the World Health Organization issued a global call to eliminate cervical cancer as a public health problem by this century [
7]. Now more than ever, effective cervical cancer control planning requires an accurate estimation of this disease.
Although studies have reported the estimates of cervical cancer burden, they are limited to confined regions or countries or used literature review methods [
8,
9]. The GLOBOCAN project regularly provides the estimates of the global incidence and mortality of cervical cancer; however, it does not provide estimates the temporal and geographical trends or for disability-adjusted life-years (DALYs) [
1,
10]. DALYs is a useful composite metric that accounts for both the mortality and morbidity associated with a disease and enables contextualization of the disease burden through cross-disease and cross-geographic comparisons [
11]. Moreover, no study has investigated the association between cervical cancer burden estimates and SDI at regional level.
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) uses a unique approach to generate estimates for all 195 countries and territories using a wide range of data sources [
11‐
13]. In this study, we used data from the GBD 2017 to estimate the global, regional, and national-specific counts, age-standardized rates, and percentage changes for incidence, DALYs, and death of cervical cancer, and their temporal and geographical trends in all 195 countries and territories by age and the SDI for the period 2007–2017. In addition, we used the SDI to identify areas with cervical cancer burden better or worse than expected. The comparison of the cervical cancer metrics among different countries or regions would provide policymakers with the required information regarding their secular trends and gaps with expected levels to allocate resources appropriately.
Discussion
This study revealed the most updated temporal and geographical trends of cervical cancer burden at the global, regional, and national level in all 195 countries from 2007 to 2017. Globally, approximately 0.6 million incident cases of cervical cancer were reported in 2017, which caused approximately 8.1 million DALYs and 0.26 million deaths. Between 2007 and 2017, that was 10 years after HPV vaccination was approved, we found although the absolute number of cervical cancer cases, DALYs, and deaths increased, the age-standardized rates for incidence, DALYs, and deaths dropped, during this period.
Our estimates are generally in line with those of the GLOBOCAN estimates. The GLOBOCAN 2018 estimated 0.57 million cervical cancer cases and 0.31 million deaths in 2018 with the age-standardized incidence and death rates of 15.2 and 7.8 per 100,000 person-years [
10], presenting an increasing trend in cases and a decreasing trend in the rates [
18]. The decreased estimates of the age-standardized incident rate as well as DALYs rate and death rate in our study reflect the increased coverage in HPV vaccination globally, the improvements in genital hygiene, reduced parity, and diminished sexually transmitted disease [
19].
We observed that the higher the SDI quintile, the lower the cervical cancer burden. The high SDI quintile were observed the lowest cervical cancer burden, and the largest decrease in cervical cancer burden was mainly attributable to the scaled-up HPV vaccination and population-based cervical cancer screening programs. A systematic review and meta-analysis revealed that a 54%–83% decline in hrHPV infection and a 31%–51% decline in precancerous lesions in young women were observed in high income countries (HICs) with high vaccination coverage [
20]. In addition, cervical cytology screening programs with a wide coverage in HICs have achieved 40%–90% reduction in cervical cancer incidence and mortality [
21,
22]. However, a challenge faced in the high SDI quintile is the presence of the highest proportion of cervical cancer cases, DALYs, and deaths in older women. Effective vaccination for older women or women with prior HPV infection is necessary in HICs.
The low SDI quintile had the highest cervical cancer burden, showing the highest age-standardized incidence, DALYs, and death rates of cervical cancer, and the highest proportion of cervical cancer cases, DALYs, and deaths in younger women. This is largely related to poverty, lack of resources and infrastructure for cervical cancer screening and treatment [
23,
24]. It’s reported that less than 3% women aged 10–20 years in less developed regions and more than 33.6% in more developed regions had received HPV vaccination [
6]. Moreover, only approximately 20% of women in less developed regions have ever been screened for cervical cancer compared with more than 60% in more developed regions [
25]. Thus, wide coverage of HPV vaccination in low-income regions are an urgent need.
Of the 21 GBD regions analyzed, the highest age-standardized rates for incidence, DALYs, and death of cervical cancer in 2017 were all found in Oceania, Central and Eastern Sub-Saharan Africa. In Oceania, specific data on cervical cancer were not available for some countries [
26] and therefore, data were extrapolated from regional estimates and countries with data available [
27]. This partially explained the highest burden of cervical cancer in Oceania. In addition, most countries or territories have a low coverage of HPV vaccination and screening programs [
28]. Implementation of effective vaccination and screening programs are priorities in these regions.
Sub-Saharan Africa had the highest prevalence of HPV infection worldwide [
29,
30]. This partly explain the high burden of cervical cancer in this region. Women in Sub-Saharan Africa have first sexual intercourse and pregnancy at an early age and have high parity, which are the risk factors of HPV infection [
31,
32]. Insufficient condom uses and multiple sexual partners are common in Sub-Saharan African women, which are the important enhancers of HPV carcinogenesis [
33,
34]. In addition, the high burden of cervical cancer is driven by other factors such as the lack of population-level screening programs, inequitable access to health services, and poverty [
29,
35,
36]. On the contrary, North Africa and the Middle East had the lowest cervical cancer burden, and Egypt, Iraq, and Kuwait had the lowest age-standardized rates for incidence and death of cervical cancer. Conservative cultural values for sex might be a critical reason because cervical cancer screening and vaccination programs are lacking in most countries of this region [
37,
38]. In addition, the low incidence rate in countries such as Iraq might be attributable to a low detection rate.
Most strikingly, we observed a large increase in the cervical cancer burden in Eastern Asia in 2007 and 2017 despite without significance, which was attributable to China. In 2017, China had the highest numbers of cervical cancer incident cases as well as DAYLs and deaths. Meanwhile, China had the highest increases in age-standardized rates for cervical cancer incidence and death from 2007 to 2017, suggesting a high public health burden of cervical cancer. Then earlier age of sexual debut in women and increased trends of multiple sexual partners and extra-marital relationships in China might contribute to the increased trends [
39,
40]. Until now, China approved HPV vaccination for a short time in 2016, with relatively low coverage [
41]. The effective control of cervical cancer remains a challenge in China, because HPV vaccination is not covered under medical insurance [
42].
At the country level, the highest age-standardized rates for incidence, DALYs, and death of cervical cancer were noted in Kiribati, Somalia, Eritrea, and Central African Republic, while the largest increases in these rates were noted in Georgia, Tajikistan, China, Jamaica, Costa Rica, and Guam, suggesting a consistently high burden of cervical cancer in these countries. Although Pap smears are highly recommended and available for women of childbearing age, screening programs coverage were still low due to lack of organization, limitations of techniques, poor quality control, and insufficient awareness [
43‐
47]. Thus, all the above should be strengthened in these countries.
We found the global cervical cancer incidence rate peaked at the age of 50–54 years, which is consistent with the GLOBACAN study [
10]. However, contrary to that study, we found an earlier incidence peak in the least developed regions (low SDI quintile). The age of newly diagnosed cervical cancer patients was younger in the low SDI quintile than in the high SDI quintile, indicating a greater cervical cancer burden in the low SDI quintile. Although age-specific data indicated that cervical cancer could affect women at a wide range of ages, we found that more than 75% of new cases and more than 50% of deaths occurred before the age of 60 years. During 2007 to 2017, the proportion of cervical cancer incident cases, DALYs, and death in elderly women increased, which could be explained by population aging [
48].
Potential linear associations between cervical cancer burden and the SDI were observed in most regions. From 1990 to 2017, the age-standardized rates for incidence, DALYs, and death of cervical cancer has decreased with the increasing SDI value. However, these rates were consistently higher than expected in some regions during the past three decades, such as Oceania, Southern and Central Sub-Saharan Africa, Central and Southern Latin America, Caribbean, and Central Europe. Potentially, these regions had worse-than-expected cervical cancer burden, indicating that these regions should be intervention priorities.
According to our knowledge, this study provides an integrated contemporary understanding of the temporal and geographical trends of the global, regional, and national cervical cancer burden by age and SDI in all 195 countries and territories during 2007 to 2017. This study also investigates the association between the SDI and cervical cancer burden, which is helpful in identifying areas where the cervical cancer burden is better or worse than expected. Further, we first used DALYs to describe the cervical cancer burden, which allowed cross-disease and cross-geographic comparisons.
The following limitations should be acknowledged. First, although the GBD 2017 attempted to collect data from all possible sources, data of some regions was limited, and the UIs were greater in areas with fewer available data. However, the updates of the GBD study will enable methodological improvements with every iteration as well as with the inclusion of the most recent data particularly in data-sparse locations. Second, the GBD estimates were based on a set of data resources such as vital registration, cancer registry, and verbal autopsy. Some low-income countries have no these sources available; thus, their estimates are based on predictive covariates or trends from neighboring countries [
49].
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.