Analysis of real-world free cervical cancer screening for eligible women in Beijing China, 2008-2018


 Background: Cervical cancer is a very common gynecological malignancy. The incidence of cervical cancer in Beijing increased rapidly, the local government launched free cervical cancer screening in 2008 as a pilot, and then the program covered all register eligible women in 16 districts since 2009. Our study assessed the free screening program in Beijing from 2008 to 2018. Methods: Analyzed the data of all women aged 35-64 years old who received free cervical cancer screening in Beijing from January 2008 to December 2018. Results: Since 2008, Beijing has conducted five cycles of cervical cancer screening among 35-64 years old women. During the period, target population has adjusted and service management kept on improved. Totally 2,624,129 person times have received the services. The average detection rate of abnormal cervical cytology was 2.3%, the rate of colposcopy referral was 1.8%, and the rate of abnormal colposcopy result was 63.5%. The detection rate of CIN2+ and cervical cancer was 208.5 / 100,000, of which 5228 cases of CIN 2+ were detected, the detection rate of 199.2 / 100,000; 244 cases of cervical cancer were detected and the rate was 9.3 / 100,000. Conclusions: Free cervical cancer screening can effectively serve the grassroots women, improve women's health awareness, and realize the early detection and early treatment of cervical cancer. The coverage of the screening population and the screening strategies need to be further explored to achieve the goal of decreasing cervical cancer incidence and mortality in the future.


Background
Cervical cancer is a very common gynecological malignancy. In 2018, an estimated 570,000 women were diagnosed with cervical cancer worldwide and approximately 311,000 women died from the disease [1].
Almost 85% of the new cases occurred in low-resource countries [2]. Cervical cancer incidence rates vary markedly across countries and regions; the estimated age-standardized (World) incidence rates have a 40-fold range worldwide. Cervical lesions are one of the diseases that seriously endanger women's health.
The 2015 WHO reported that both total incidence and death of cervical cancer in China ranked the second in the world [3]. It remains one of most common cancers and the cause of cancer-related death in women across the globe. Over the next 12 years (2018 to 2030), the annual number of new cases of cervical cancer is expected to increase from 570,000 to 700,000. During that same period, the annual number of deaths will increase from 311,000 to 400,000. More than 85% of those affected are young, poor, undereducated women of color who live in the world's poorest countries. Many are also mothers of young children whose survival is subsequently truncated by the premature death of their mothers [4].
China's national cancer registration data from 1988 to 2012 show that the overall incidence of cervical cancer in the country has slowly decreased from 5.04 per 100,000 in 1988, but it has continued to rise since 1999, at 14.93 per 100,000 in 2012. The fth of the incidence. A national retrospective survey of causes of death shows that the female cervical cancer mortality rate in China was stable from 2006 to 2012, ranking seventh among female cancer deaths [5]. The incidence of cervical cancer in Beijing was 3.28 / 100,000 in 2000 compared with 9.23 / 100,000 in 2009, totally increased 181.8% and annually average increased 12.1%. Cervical cancer has become the fastest growing malignant tumor in women, its incidence ranked from the 13th in 2000 to the 9th in 2009 [6][7][8][9]. So Beijing launched free cervical cancer screening in 2008 as a pilot, and then the program covered all register eligible women in 16 districts since 2009.
In this study, we assessed the free cervical cancer screening for ve cycles among eligible women in Beijing to provide evidence for policy decision on further development of the program in the future.

Study population
Eligible women registered in Beijing received free cervical cancer screening once every two years. In Beijing, the program had gone through ve cycles from 2008 to 2018, and served 2,624,129 person times.
All women were informed consent before participating in the screening. Details are in Table 1. Cervical cytology test, colposcopy, and histopathology is the basic procedures for screening, diagnosis and management of the screening program in Beijing. The screening procedure included recruitment by informed consent, gynecological examination, cervical cytological test and medical advices for suspicious cases detected on diagnosis and treatment [9].
Women with ASCUS and above on cervical cytological result would refer to colposcopy and some of them received pathological examination if necessary. During the period, screening programs kept on improving depending on the epidemic of the disease and the social development. In Beijing,139 community health centers and 31 hospitals undertakes the screening and referral services.

Quality Control
Gynecological examination. Check the environment, facilities and items at the screening site, observe the operation process and form lling of all gynecological screening staff, and review 5-10% of screening women on set.
Cytological test. Cervical cytology played an important role in the screening that is critical for precancerous and cervical cancer diagnosis and treatment. Professional and technical ability on cervical cytology was uneven among districts and many domestic liquid-based cytological reagents applied in clinics were lack of uni ed supervision and quality control. In order to ensure the quality of cervical cytology, Beijing has made many efforts on cervical cytology quality control, like formulating technical guideline, staff training and regular assessment, establishing a quality control system for cervical cytology reading,which has played vital roles in improving the quality of cervical cytology.
Pap smear or LBC were used in free cervical screening and the personnel who quali ed for cervical cytology screening in this project interpreted them. Randomly sampled 5% negative and 20% positive smears for experts to review.
Colposcopy. Colposcopy, as an important examination for further evaluation of suspicious cases detected by screening, is the key step of cervical cancer screening. In Beijing, the referral medical centers provide colposcopy and pathology services. The colposcopy work guidelines in Beijing not only emphasize standard operation, but also emphasize the suspicious cases management,which means besides providing an examination, these centers must follow up the cases and carry out regular quality control.
Those with cervical cytology ASCUS and above will undergo colposcopy; experts randomly reviewed 10% normal and 5% abnormal cases for evaluating.
Pathological examination. Some women with colposcopy abnormality will received pathological examination if necessary. Data collected from the report of colposcopy biopsy, LEEP, CKC and surgery.

Results
Briefs of cervical cancer screening in Beijing from 2008 to 2018 During 2008-2018, totally 2,624,123 eligible women were screened in Beijing. During the past ten years, the screening programs and procedures updated and improved continuously. Coverage rate remain steadily during 10 years in Beijing, the mean was 17.9% (16.6%-19.4%). The composition of participation in screening are relatively higher among women of 45-59 years of age, education level below junior high school, and those in rural, as shown in Table 2.   Women with cervical cytology of ASCUS and above will refer to colposcopy that accounted for 1.8% in the four cycles. In addition, women with suspicious symptoms will undergo colposcopy to avoid missed diagnosis as much as possible.   Table 5.

Discussion
WHO emphasis that effective screening and treatment of pre-cancer for women aged 30 years and above can prevent women from developing cervical cancer [5]. Different countries and regions will choose their own screening strategy adapt to the variable local conditions and economic conditions.
In Beijing,data showed that the highest disability weight per thousand people of cervical cancer were among 35-65 years old, the morbidity and mortality in the 25-35 age group were not high, which means less than 35 years old screening in Beijing was not cost-effectiveness. Therefore, the local government kept on improving the screening program to adapt to the socio-economic development. In recent guidelines, WHO recommended that the minimum age limit for cervical cancer screening in developing countries should not be less than 30 years old as well [10][11] .
Among those participated in the screening program, women below junior high school accounted for more than 60%, women living in rural accounted for more than 60%, and women older than 45 years old accounted for more than 70%. The majority was middle-aged and older women, unemployed, and agricultural population. Our study showed that more women in rural would receive the screening services than those in urban because most women living in urban received regular gynecological examinations organized by the working places. The program bene t women of low income especially [12], who could hardly covered by the regular physical examination supported by the working places. Therefore, they are very active in this screening. From 2008 to 2018, totally 2,624,129 person times received the screening services, accounted for about 15-20% of all eligible women, which was almost the same as the township screening participate rates in China [13]. Not only the program improved the health outcomes but also increased the equity.
The China Women's Development Program (2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020) proposes that the regular screening rate for women's common diseases should reach more than 80%, try to improve the rate of early diagnosis and treatment of cervical cancer and breast cancer, reduce mortality [14]. The coverage rate of the screening in Beijing is only less than 20% especially in urban compared with the size of eligible women in Beijing, which was far lower than that of developed countries. As WHO reported, only 22 countries, mainly with high income, reported screening programs achieving 70% coverage or above. The majority of countries report participation rates below 50%, some as low as less than 10%, due to lack of organized programs, ineffective population outreach, fragmented service delivery, unavailable infrastructure and limited nancial resources. According to the household registration survey, for cervical cancer, the main reason of refusal to participate in screening is variable in different countries [15][16]. Barriers to increased coverage relate to both supply and demand, with the latter including cultural, social and nancial barriers. Further, many countries face challenges relating to poor-quality screening and follow-up of positive cases [17]. In our investigation, lack of time and long distance was the barriers for women received the screening services. In addition, data of women's health check-ups are not included because they were not supported by government funds. A modelling study in China suggest that population coverage of screening is more important than the frequency of screening, and the once in a lifetime screening at age 45 years might be the best available strategy, given the insu cient budget. The optimal age at which to screen is driven from the distinctive age-speci c prevalence of CIN2 + and high-risk HPV in Chinese women [18]. We also notice that eligible women accepted screening had lower composition ratio in Beijing, yet the ratio should be more than 70%, which has mentioned by WHO in order to expect eliminating cervical cancer worldwide [19].
Swedish practice has proved that cervical cytology smear test helps to detect precancerous lesions earlier, greatly reducing the risk of cervical cancer. [20] Abnormal detection rate of cervical cytology in Beijing was 2-3%. In the 5th cycle, the rate was almost 3% that was the same as Chinese women in rural accepted screening services, but lower than the developed coastal areas in China [21][22], even far lower than 5.7% of liquid-based cytology and 4.5% of Pap-smear in Asia [23]. The detection rate of abnormal cervical cytology was not high enough to detect precancerous lesion or cervical cancers as much as possible. The screening program has carried out in Beijing for a decade; the technical of cervical cytology is still uneven. The rate was much lower than that of the screening program in US, Japan and Turkey [24][25][26]. Meanwhile, we must soberly recognize that the rate is far from the Chinese experts' speculation that abnormal detection rate of cervical cytology among the eligible women should be 5-7% [27]. Moreover, it had affected the colposcopy referral rate for ASCUS result. The highest colposcopy referral rate for ASCUS result was 2.7% in the fth cycle, much lower than that in Canada and European countries [28].
In our study, cases of ASC-US accounted for 1.8% of all cytological tests. The ratio of ASC-US to squamous intraepithelial lesions was 2.87, suggesting the proportion of TBS diagnosis was acceptable. There was no over diagnosis of ASC-US [29].
Screening program in China started late. Empowerment of cytopathologists and cytology technicians is a long-term effort. In Beijing, grassroots personnel mainly undertook cervical cytology sampling and lm readings. Our quality control showed although the capabilities improved apparently from the beginning of the screening program, while sampling, lm production and dyeing, varieties of personnel diagnosis on lm reading remain the affecting factors of the cytological test quality in Beijing yet. We should exert to further empower the staffs and improve the quality control system especially on the detail of cervical cytology production, staining and reading [30].
In the ve screening cycles, the detection rate of cervical cancer and precancerous lesions has continued to increase that was much higher than the national level of 124.9 / 100,000. The effectiveness of screening is not limited to early detection and treatment of a small number of cancer patients, but more importantly, to nd a large number of patients with precancerous lesions, to release them from expensive cervical cancer treatment costs, and to achieve good social and economic bene ts. In our study, the detection rate of precancerous lesions has continued to increase, from 70.4/100,000 to 259.4/100,000; while the detection rate of cervical cancer has been declining, till the fth cycle it was 5.1/100,000. The detection rate of cervical cancer in Beijing was almost the same as cervical cancer incidence in Beijing. The early diagnosis rate was above 90% that remained in high level from the very beginning of the program. It kept on increasing and peaked in the fth cycle, which was higher than that of the rural women-screening program in China.
The incidence and mortality of cervical cancer have continued to decline in many countries and regions due to organized screening for decades. In US, the incidence of cervical cancer has decreased by more than 50% in the past 30 years, and the mortality rate reduced from 5.55/100,000 to 2.3 /100,000 [31]. As Beijing Institute for Cancer Research and Beijing Center for Disease Prevention and Control reported, cervical cancer incidence and mortality kept on increasing in Beijing within 10 years; incidence (ASR world) was 5.21/100,000 in 2008 and 6.01/100,000 in 2017. Organized screening carried out in Beijing is only 10 years,with the improvement of MCH system and the advancement of cervical cancer screening and diagnosis and treatment technology, the incidence fell from sixth in the 1980s to tenth in 2017 mortality dropped from rst in 1985 to eighth in 2010 and APC of incidence (ASR world) in Beijing kept on decreasing within 10 years, 3.96% in 2005-2013 and − 0.61% after 2013 [32].
Our study has many strengths. First, the program was one of the services providing in primary health care system in Beijing that was practical and suitable in Chinese primary health services. By taking on screening, grassroots service capabilities have been empowered; by participating in screening, women's health awareness strengthened; by implementing screening, cancer and precancerous lesions have been detected as early as possible to reduced morbidity and mortality. Second, it is the comprehensive description and data analysis of free cervical cancer screening of all eligible women in Beijing from the very beginning. The sample size was large covering 16 districts all over Beijing that can provide evidence for the national screening program improvement.
In 2019, Beijing updated the program on cervical screening [33]. On one hand, the government integrated health check-ups and data targeted at the eligible women; applied co-testing in cervical cancer screening.
These updating aims at improving screening strategy. On the other, social mobilize to improve the women's awareness and participation. We hope that an optimal screening model suitable for the epidemiological status of cervical cancer and the socio-economic development in Beijing will maximize the detection of cervical lesion, achieve the goal of early found, early diagnosis and early treatment.

Conclusions
Free cervical cancer program in Beijing has seen progresses in the decade with the increasing detection rate on precancerous lesion and cancers and the early diagnosis rate that bene tted the eligible women especially those with low income. We cannot overemphasize social mobilization to increase screening coverage. More emphasis should be put on the rst step of the screening to nd the abnormalities as much as possible. More efforts need to explore a suitable screening strategy in Beijing to implement cervical cancer elimination in the coming days. Figure 1 Flowchart of screening.