a Department of Epidemiology and Statistics, The Institute of Basic Medicine, Shandong Academy of Medical Sciences, 89 Jingshi Road, Jinan 250062, PRC.
b Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Reprint requests to: David B Thomas, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N MP-474, PO Box 19024, Seattle, WA 98109-1024, USA.
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Abstract |
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Methods Three retrospective surveys of all causes of death in 19701974, 19851989 and 19901992 in Shandong were carried out. An age-period-cohort analysis based on similar survey data from Qixia, a county in Shandong, from 1970 to 1994 was performed. A correlation analysis between prevalence of syphilis and cervical cancer mortality rates three decades later was conducted. A cross-sectional survey of risk factors for cervical cancer was conducted in 1991 in one city and 12 villages in the province.
Results A marked decline in cervical cancer mortality rates was observed from 1970 to 1992 and in successive birth cohorts from 1892 to 1927, and rates remained relatively constant in subsequent birth cohorts through that of 1952. The decline in these rates was strongly correlated with a decline in positive serological tests for syphilis 32 years previously. The percentages of women with selected risk factors were lower in younger women (3054 years) than in older women (5569 years) in both cities and rural areas.
Conclusion These trends are compatible with a decrease in risk of exposure to sexually transmitted factors at an early age after the founding of the People's Republic of China in 1949, and a decline in lifetime duration of exposure to possible co-factors in successive birth cohorts who reached sexual maturity before that time.
Keywords Cervical cancer, decline mortality, age-period-cohort analysis, correlation study, cross-sectional study
Accepted 20 October 1999
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Introduction |
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Materials and Methods |
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Serologically detected cases of syphilis in women between 1954 and 1960 were obtained from the Shandong Dermatological Diseases Institute.6 A correlation analysis between mortality from cervical cancer 19861992 and rates of syphilis 19541960 was performed (assuming a latent period of about three decades from exposure to risk factor to diagnosis of cervical cancer).
In order to investigate temporal changes in the prevalence of risk factors, a cross-sectional study conducted in conjunction with a Pap smear screening programme was carried out in one city, Jinan, and in 12 villages located in three other counties of the province from 1 January 1989 to 30 May 1991. A team of gynaecology and health workers was instructed to screen all women and administer a questionnaire. All eligible women were invited to participate, and 61% and 70% agreed in the city and rural areas, respectively. Each subject was interviewed using a standard questionnaire which took approximately 25 minutes to administer. Information was sought regarding socio-demographic characteristics, marital and reproductive history, cigarette smoking, and personal and genital hygiene. To assess the changes in some risk factors with time, the data for women in the two age groups 3054 and 5569 were compared. These two age groups roughly correspond to women who reached sexual maturity before and after major social policies were instituted by the Chinese government in the 1950s.
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Results |
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The mortality for cervical cancer per 100 000 women, adjusted to the world population, was 5.57 during 19851989, compared with 21.11 during 19701974, which is a 73.1% reduction. The mortality for cervical cancer was 4.40 during 19901992, which is a 79.1% reduction compared with that of 19701974.
The mortality rates for each year during 19701974 and 19851992 were 20.90, 20.73, 21.68, 21.63, 20.71, 5.31, 5.80, 6.44, 5.93, 4.49, 4.55, 4.00 and 4.65 per 100 000 women adjusted to the world population, respectively. The decline in cervical cancer mortality was observed in each surveyed area of the province, except Xuecheng County, which had a low incidence rate in 19701974.
The age-specific mortality rates of cervical cancer in Shandong Province during the three time periods are shown in Table 2. The age-specific rates for women over 35 decreased over time. The rates for younger women tended not to decline from 19851989 to 19901992.
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Discussion |
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The results of age-period-cohort analysis indicated that the decreasing mortality is largely a cohort phenomenon. Pap smear screening is an effective method for early detection of cervical cancer. In Shandong Province a Pap smear screening programme started during 19701972.6 In all, 343 858 women were screened in the early 1970s, which accounted for only 1.5% of the female population. After that, there was no financial support for screening by the government, so screening was conducted in only in a few areas by some individual hospital doctors.
We analysed 259 newly diagnosed cases treated in Shandong Tumour Hospital from January 1990 to June 1991. The percentages of cases clinically classified with early local, locally invasive, and metastatic disease were 0.8%, 29.3% and 69.6%, respectively. We also analysed the survival time for the patients who suffered from cervical cancer in Cangshan County from 1975 to 1985. The number of patients each year were 44, 45, 43, 57, 35, 34, 25, 23, 24, 19 and 19, respectively. Two-year survival probabilities were 0.22 and 0.30 for 19751979 and 19801985,22 respectively. (Because of economic problems the majority of patients could not get radiotherapy.) This small improvement in survival cannot explain the decline in mortality from cervical cancer in Shandong. The decline in mortality mainly represents a decrease in incidence of the disease, and is not a result of early detection followed by treatment.
The decline in incidence is most likely a result of the marked social changes and health programmes initiated by the Chinese government after the founding of the People's Republic of China in 1949. Soon after the new government was established, prostitution was outlawed and brothels were closed. Health facilities were soon established in factories and other work units, and specific public health programmes were initiated to screen for syphilis and treat this and other venereal diseases. In the mid-1960s, contraception became widely available, and in 1975 a law was passed restricting the number of children to one per family in cities, and to less than two for rural areas. Consistent with these measures, the cross-sectional survey showed that, compared to older women, those 3054 years of age in 1991 were better educated, had fewer children, and older at marriage. They also had greater use of IUD and hormonal contraceptives, and they smoked less.
Detailed epidemiological studies have shown that sexual activity is a major factor in the genesis of cervical cancer.2346 Increased risk has been associated with age at first coitus,23,27,28,30 extramarital sexual relationships,23,25,26,30 history of husband having visited prostitutes,29,38 low educational level,23,26,29 multiple full-term pregnancies,23,24,25,30 and infection with such sexually transmitted agents as herpes simplex virus type 2 (HSV-2),24,32,34 chlamydia,29 and trachoma.29 The evidence associating certain types of human papillomaviruses (HPV) with cervical cancer is particularly strong,25,33,3646 and these viruses are generally accepted as important and probably necessary causal agents for cervical carcinoma.4246 The other sexual variables likely reflect the sexual mode of transmission of these viruses. However, few women who are infected with these viruses actually develop invasive disease, clearly indicating that co-factors are involved in either enhancing or reducing the carcinogenic effect of HPV.47 The observation in this study of a decline in mortality rates from cervical cancer has implications for our understanding of the multifactorial aetiology of cervical cancer. The decline occurred in birth cohorts that reached sexual maturity prior to 1949. It is unlikely that social changes before 1949 influenced exposures to risk factors for cervical cancer in a favourable way, and to a greater extent in successive birth cohorts. A more likely explanation is that the older a woman was in 1949, the longer she had been at risk of exposure to unfavourable risk factors. Conversely, the women in more recent cohorts would have spent a longer period after puberty in a more favourable environment.
Exposure to oncogenic types of HPV occur after initiation of sexual activity. Women in successively earlier cohorts would thus have spent successively longer periods of time at risk of infection. However, there is some evidence that early infection is important and that invasive cervical cancer usually arises decades after initial infection,23 and repeated re-infection therefore may not be as important as co-factors that encourage persistence of infection. These co-factors may include high parity and poor nutritional status, both of which were altered in and after 1949 in a way compatible with the observed decline in cervical cancer mortality; i.e. shorter exposure to these co-factors in succeeding birth cohorts would explain the decline in rates in these same cohorts. This implies that the co-factors act not to increase susceptibility to an initial (early) HPV infection, but to enhance persistence of HPV infection for a prolonged period of time.
The low rates of cervical cancer in women born in 1927 and after, who would have been 22 or younger in 1949, were just entering their sexually active years, and were subjected to the enforcement of laws against prostitution and extramarital sexual relationships, which would have greatly reduced transmission of HPV. Possibly unfavourable co-factors, such as use of steroid contraceptives and induced abortion, which became widely available after 1949, and cigarette smoking, which declined with age in Shandong Province, would not be expected to alter risk in the absence of HPV. Their influence on rates would be expected to be minimal even if shown to be associated with cervical cancer in other countries where HPV rates are higher than they presumably were in China.
In recent years, rates of sexually transmitted disease have increased in China.48,49 If this trend continues, an increase in cervical cancer rates will likely follow.
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