During the past decades, incidence rates of cervical cancer appear to be increasing in Guangzhou. However, the incidence rates of cervical cancer have fallen in some high-income settings, including north America, northern and western Europe, and Australia and New Zealand, and South Korea ,which were probably the result of successful cytological screening . Our study showed increasing trends of cervical cancer incidence in Guangzhou from 2004 to 2018, which were driven by cohort and period effects. Similar increasing trends were also observed in other regions of China , Russia, some countries of Central and Eastern Europe and Africa[7, 21, 22]. As high-risk human papillomavirus (HPV) types are necessary cause of cervical cancer, the increasing cervical cancer incidence in Guangzhou could be due to the following reasons. The first reason is the growing prevalence of high-risk HPV, which was high to 20.2% in female population during 2008-2017, and the other might be due to screening.
Although urban regions had the highest incidence rate of cervical cancer in Guangzhou in 2004, the increase in incidence was more sharply in county regions during past decades. The incidence in county regions has exceeded that in urban and suburban regions since 2010, and the similar patterns were also reported in Shanghai. The crude incidence in urban regions were increased but showed no change after age-standardization, indicating that the increase was mainly due to the change in age structure (i.e., population ageing). The incidence showed a downward trend in the age groups of 20-49 years, and an increasing trend in the age groups of 50-74 years, which were consistent with the increasing risk in successive birth-cohorts born between 1922 and 1966s and decreasing risk after 1966s . Unfortunately, no period effects were evident to support the effect of opportunistic urban-wide screening in the urban regions. In Hong Kong, despite well-organized population-based screening of cervical cancer has never been introduced, the observed decrease in incidence could be attributable to an increase in opportunistic screening from 1972 to 2006[26, 27].
The crude and standardized rate of cervical cancer incidence increased in suburban and county regions, which increased mainly in the age group of 50+ years. The increase was more sharply in county regions than suburban regions. The APC analysis in our study showed that period effects increased from 2004 to 2018 in suburban and country regions, which was consistent with the implication of the local screening program. In Guangzhou, the local government has enormous investment in cervical cancer screening since 2009, and such program was main launched in urban and country regions, and some of the suburban regions. The period effect might be explained by the following reasons. This project may not have enough coverage, and were only conducted at one time point without follow-up. The birth cohort between 1922 and 1966 showed the same increasing trend in different regions, but the age group of the birth cohort decreased later in suburban and county regions than urban regions. The increasing cohort effects on the cervical cancer incidence rate in those born during 1922-1966 could be due to the more open sexual behavior after the reform and opening up after the 1980s and the lack of opportunistic screening conditions. With the improvement in health awareness and the increase in opportunistic screening, especially the occupational physical examination of many companies began to include cervical cancer screening in routine physical examination, the cohort effects on the incidence cervical rate has become decreasing since 1970s. The peak of the cohort effects varies across regions, which may be due to urban-rural inequity in medical resource allocation and health awareness in urban-rural regions.
Besides the incidence increase of SCC subtype that mimicked the overall trend, a rapid rise in the incidence of AC subtype was observed. An increase in adenocarcinoma incidence rates has also been observed in other countries like the United States and Western Europe, even the SCC incidence rate has decreased. The sensitivity of Pap testing is higher for SCC and its precursors compared to AC. The rates of SCC may have increased in line with AC if the screening not been widely available or disseminated. SCC did not increase as much as AC in Guangzhou, which may be due to this reason.
Our analysis shows that opportunistic screening and the local government’s efforts in screening in rural regions have a partial effect. Greater efforts are needed to curb the continued rise of cervical cancer. A survey showed that only 20% of the women interviewed reported having ever had a Pap test and even less of those who received continuous screening. Also, women in rural regions were less likely to take a Pap test than those in urban regions . The World Health Organization (WHO) recommends that all women between the ages of 30 and 49 years should be screened for cervical cancer at least once. The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with contesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable). Individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more, with severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening. Thus, based on our results and international experiences, we suggest that women aged 30 years or older should begin to be screened. Moreover, free Cervical Cancer Screening Program should be expanded to all regions of Guangzhou as a major public health benefit as early as possible in the face of continuously increasing incidence rate in older age groups. Systematic evaluation for the effectiveness of cervical cancer screening should be performed periodically and regularly.
There are several factors that might influence the participation in cervical cancer screening, including lack of knowledge and awareness of cervical cancer screening and its benefits, fear of pain and being diagnosed with cervical cancer, embarrassment, the lack of husband’s support for screening, and cultural factors[33, 34]. The cytological screening of cervical cancer requires high quality expertise and equipment. Rural county regions in Guangzhou often do not have a department of cytology or pathology. Individuals in rural regions need go to city hospital to screen. Therefore, a relevant health education policy should be developed, which aimed at raising women’s awareness on the risk factors of cervical cancer and the importance of early diagnosis. At the same time, the medical service capacity in rural regions should be enhanced and medical resources should be optimized.
Since the world’s first HPV vaccine became available in 2006, the authorities in China finally approved Cervarix (GlaxoSmithKline Biologicals SA, Rixensart, Belgium) in 2016, Gardasil 4 (Merck & Co, Inc, Kenilworth,NJ, USA) in 2017, and Gardasil 9 (Merck & Co, Inc) in 2018 in mainland China. To expand vaccination, national level HPV vaccination strategy should be developed. Meanwhile, health education should be strengthened to raise public awareness on the efficacy of
HPV vaccine in order to increase vaccine uptake. Moreover, the evaluation of HPV vaccine’s effectiveness and safety should be initiated.
Limitations of our study include lack of information on stage at diagnosis for most cancer cases and the hysterectomy data. Moreover, due to the lack of data, limited risk factors that might have affected cervical cancer incidence were examined. Hence, further studies are needed to explore factors explained the disparity of cohort and period effects between different regions in Guangzhou. Strengths of this study include our population-based analysis of the incidence trends for cervical cancer included high-quality and long-term surveillance data in Guangzhou, one of biggest cities in China. In addition, the observation period was relatively long (from 2004 to 2018) including the year the government started cervical cancer screening in suburban and urban regions. On account of the accurate and representative surveillance data, our results are convincing.