Discussion
Cancer is a leading cause of death and disability worldwide, especially
in women.8,9Gynecologic cancers which have
negative effects on the physical and psychological health of patients,
seriously threaten women’s life and health. According to GLOBOCAN 2020
Project data, cervical cancer, uterine cancer, and ovarian cancer are
among the top 10 common cancers in females worldwide.1China is the world’s most populous country with around 685 million
women. Approximately 214,400 new cases of gynecologic cancer occurred in
2015, and there were about 74,800 deaths from gynecologic cancer in
China.10 Therefore, it is of great social significance
to comprehensively understand the epidemic trends and patterns of
gynecological cancers in China. In this study, we not only assessed the
prevalence of gynecologic cancers in China, but also systematically
analyzed trends of incidence, mortality, DALYs and proportions
attributable to risk factors for gynecological malignancies from 1990 to
2019. In addition, we predicted incidence and mortality rates for
gynecologic malignancies from 2020 to 2030. This is one substantial
study to investigate the long-term trends of morbidity and mortality for
gynecologic malignancies in China and to assess DALYs rates and
proportions attributable to risk factors for gynecological malignancies
from 1990 to 2019.
The global costs associated with
cancer are significant and are estimated to comprise 2-4% of the annual
gross domestic product (GDP). The majority of the world’s cancer burden
occurs in low- and middle- income countries (LMICs).11In addition to social and economic burden on women and their family,
gynecologic malignancies play negative effects on women’s self-concept,
body image, sense of femininity and sex life.12-16Most of the people in China have medical insurance, however cancer costs
are only partly covered by insurance. Medical costs are still problem
for patients with gynecologic malignancies. Due to women’s increasingly
important roles in the family and society in China, gynecologic cancer
patients are more likely to suffer from anxiety and depression. China is
the most populous country in the world, so cancer patterns in China is
an important focus of public health. China is undergoing a transition
period from being a developing country to a developed country, with a
large number of female residents, it is of great social significance to
summarize and analyze the epidemiological patterns of
gynecologic malignancies in China.
The incidence, mortality, disability-adjusted life-years (DALYs) could
be used to measure disease and economic
burdens.7,17-20 The burden of cancer incidence and
mortality is growing rapidly worldwide. Around the world, the total
incidence and mortality of gynecologic cancers increased sharply from
1990 to 2019. From 1990 to 2019, the numbers of incidence cases, deaths
and DALYs of cervical cancer, uterine cancer and ovarian cancer all
significantly increased, which is consistent with the reports in another
paper.7 As shown in Table 1, the ASIRs and ASDRs of
these three types of cancers exhibited different epidemiological
patterns. We analyzed numbers and rates of incidence, death and DALYs of
cervical cancer, uterine cancer and ovarian cancer by age in 2019 in
China. Data showed that the numbers of incident cases and DALYs of
cervical cancer, uterine cancer and ovarian cancer reached the peak
among the female population aged 50-54 years. Meanwhile, the peak
numbers of deaths of cervical cancer, uterine cancer and ovarian cancer
appeared at aged 50-54, 65-69 and 65-69 years, respectively. More
screenings and attention should be paid to Chinese women aged 50-69
years. The results showed that the high-risk group of gynecologic cancer
was middle-aged and elderly women in China; The middle-aged and elderly
population is the key population to carry out comprehensive prevention
and control of malignant tumors. It is necessary to strengthen the
health examination, health knowledge education, tumor screening, early
diagnosis, early treatment, tumor registration and follow-up of the
middle-aged and elderly population. The prevention and treatment of
gynecologic cancer is a long-term and arduous task. On the basis of
improving the monitoring of cancer incidence and death, we should fully
analyze the types of high-incidence cancers and high-risk factors in
different age groups, and adopt targeted prevention and treatment
strategies with overall consideration, so as to obtain a good effect of
tumor prevention and treatment.
We explored DALYs rates and proportions attributable to risk factors for
gynecological malignancies from 1990 to 2019, in order to provide
scientific basis for effective prevention and intervention of cervical
cancer, uterine cancer and ovarian cancer. Cervical cancer is one of the
leading causes of cancer-related deaths in women
worldwide,21 meanwhile, it is the most common
gynecologic cancer in China. High-risk subtypes of the human
papillomavirus (HPV) cause almost all cervix
cancers.22 Persistent infection of the lower genital
tract by one of the high-risk HPV (hrHPV) types is the “necessary”
cause of cervical cancer. HPV16 and 18 are associated with approximately
71% of cervical cancer cases, while 31, 33, 45, 52 and 58 are
associated with another 19% of cases.23-25 High
proportion of sexually active women become infected with some human
papillomavirus type by age 25 years, but most infections resolve
spontaneously.26 It suggests that the infection is
predominantly transmitted through the sexual activity. Our results
showed that, the DALYs rates of cervical cancer attributed to unsafe
sexual activity were the highest in all age-specific groups, and the
DALYs rates attributable to unsafe sexual activity showed a downward
trend in recent years. However, the DALYs proportion of cervical cancer
attributable to unsafe sexual activity was 100% continuously. Studies
show that cervical cancer is positively correlated with premature sexual
life, excessive sexual life, multiple sexual partners and unclean sexual
life. The risk of cervical cancer in women with initial sexual behavior
≥ 21 years old is lower than that in women with initial sexual behavior
aged 15~16 years old.27 It is an
effective measure to improve people’s awareness of cervical cancer
related knowledge, HPV vaccine and cervical cancer screening and improve
their awareness of prevention and control in China. Cervical cancer
screening has become one of the most common gynecological screening
programs in China.28 This is of great significance in
the early diagnosis of cervical cancer. Studies have shown that smoking
and passive smoking are also related to the occurrence of cervical
cancer and precancerous lesions. The mechanism may be that the
concentration of nicotine in cervical mucus of smoking women increases
significantly, consumes a large number of Langham cells, and leads to
the reduction of cervical immunity. According to relevant statistics,
the risk of cervical cancer increased 11.8 times in patients with
passive smoking time ≥5 h/d.29 The results of our
study show that the DALYs rates of cervical cancer due to smoking showed
a downward trend in above 60-year-old groups, and smoking’s contribution
descended in 2019 compared to 1990 (shown in Figure 3). This indicates
that health education, lifestyle improvement and anti-smoking laws must
be carried out throughout the comprehensive prevention and control of
cancer. This has important implications for improving women’s
reproductive health.
Studies have found that obesity may be an important factor affecting the
occurrence and development of uterine cancer.30-32Body-mass index (BMI) was positively correlated with the risk of
endometrial cancer, and the risk of endometrial cancer in overweight and
obese people was 2.45 times and 3.5 times higher than that in normal
people, respectively.33 In a prospective study of 36
755 women, there was a strongly positive and linear association of BMI
with the risk of uterine cancer.32 Our results
indicated that the DALYs rates of uterine cancer due to high body-mass
index were higher between 50 and 69 years. In addition, proportions of
DALYs attributable to high body-mass index for uterine cancer were
higher in 2019 than in 1990 in all age-specific groups. Previous data
also showed that compared with normal BMI, 181 genes involved in lipid
metabolism, fatty acid metabolism and metabolic signal transduction
pathway were up-regulated or down-regulated in obese patients with
uterine cancer.34 In recent decades, the
implementation of comprehensive staging surgery for uterine cancer, the
application of minimally invasive technology, reasonable adjuvant
chemotherapy and radiotherapy, and comprehensive treatment for advanced
patients have greatly improved the prognosis of patients. However, the
pharmacokinetic changes and metabolic abnormalities caused by obesity
will reduce the chemotherapy effect of uterine cancer and cause poor
prognosis.35 Improving the risk awareness of high-risk
groups for uterine cancer, carrying out active and effective screening,
changing adverse lifestyle, and early intervention for metabolic
diseases can reduce the risk of uterine lesions, and effectively reduce
the incidence and mortality of uterine cancer.
The result showed that the incidence and death rate of ovarian cancer
showed an upward trend in overall groups in China from 1990 to 2019. As
one of the deadliest cancers, the early diagnosis of ovarian cancer is
very difficult. When patients are diagnosed, they are often in the
middle and advanced stage, which is not conducive to the treatment and
prognosis of patients. The 5-year survival rate will not exceed
30%.36 Previous studies suggested that the risk
factors for ovarian cancer mainly included family genetic history,
fertility factors, menstrual history, body mass index, obesity,
lifestyle, diet, hormone replacement therapy and so
on.37-41 Other studies have shown that organic dust,
asbestos, and talcum powder are also risk factors for ovarian
cancer.42,43 We analyzed the DALYs rates and
proportions attributable to risk factors for ovarian cancer in China
from 1990 to 2019. As shown in Figure 3, the DALYs rates of ovarian
cancer attributable to high body-mass index, high fasting plasma glucose
and occupational asbestos exposure had an upward trend from 1990 to
2019. In addition, proportions of DALYs attributable to high body-mass
index for ovarian cancer were higher in 2019 than in 1990 in all
age-specific groups. This seems to suggest that with the increase of
China’s GDP and the improvement of people’s quality of life, the
malignant tumors caused by metabolic diseases are on the rise. It is
necessary to formulate relevant strategies, including promoting
exercise, healthy diet, regular screening, controlling metabolic
diseases and so on. The proportion of DALYs attributable to occupational
asbestos exposure was slightly lower in 2019 than in 1990. Although most
countries prohibit the use of asbestos, millions of people still work in
factories exposed to asbestos, and at least 90000 people die each year
from asbestos related diseases or cancer diseases.44Governments should increase efforts to limit the production and use of
asbestos, and find alternatives to reduce asbestos exposure. Regular
occupational disease screening and physical examination for women at
risk of asbestos exposure also contribute to the prevention of ovarian
cancer.
According to the data forecast, there will be 28.4 million new cancer
cases worldwide by 2040, an increase of 47% compared with 19.3 million
cases in 2020.1 The global economic burden on cancer
will be heavy. Based on GBD data of gynecological malignancies from 1990
to 2019 in China, we predicted the incident cases and deaths in the next
eleven years. Results showed that the numbers of incident cases and
deaths of cervical cancer, uterine cancer and ovarian cancer should
continue to increase from 2020 to 2030. This indicates that the economic
burden on gynecological malignancies in China will further increase in
the next decade. We further analyzed the trends of three major
gynecological malignancies, in order to facilitate government
departments to adjust their budgets, better allocate prevention and
research funds, and adjust the total prevention expenditure. The
predicted new cases of uterine cancer have the steepest rising slope,
which is expected to exceed the cases of cervical cancer in 2030.
Meanwhile, the growth of uterine cancer deaths also had the steepest
slope, followed by ovarian cancer and cervical cancer. In recent years,
with the rapid development of China’s economy, people’s living habits
and diet structure have changed greatly. With the increase of metabolic
diseases, uterine cancer also has an increasing incidence rate and
younger onset trend. Uterine cancer has become a serious problem
endangering the health of Chinese women. It is urgent to establish
effective screening methods to realize the early diagnosis and treatment
of uterine cancer. Screening guidelines for uterine cancer have been
developed in the United States,45 the United
Kingdom,46 Germany,47 and other
countries. In addition to carrying out primary prevention, changing
lifestyle and reducing risk factors, it is also important to carry out
secondary prevention with periodic screening among high-risk groups in
China. According to China’s Expert Consensus on Screening and Early
Diagnosis of Endometrial Cancer, screening is recommended for women over
45 years old, especially those with metabolic syndrome such as diabetes
and obesity, history of estrogen use, tamoxifen treatment, and family
history of cancer. Molecular classification was applied to uterine
cancer when the results of the Cancer Genome Atlas (TCGA) project were
published.48 This molecular classification is
important for diagnosis, prognosis and treatment of uterine cancer.
There are several limitations of the current study. First, the
predictions were based on the GBD Study, in some cases, primary data was
lacking. The quality of original individual registration data greatly
affects the accuracy and stability of database estimation, and the
missing or false data may lead to bias. This bias was also kept low due
to the GBD study’s many measures to reduce this bias, such as correcting
incompleteness, underreporting and misclassification, as well as
reassigning garbage code, and so on. Second, due to the limited
information in the GBD database, the burden of gynecological
malignancies caused by other risk factors cannot be fully evaluated.