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.