The decline in the mortality rates of cervical cancer and a plausible explanation in Shandong, China

Hui-qing Lia, Shi-quan Jina, Hai-xiu Xua and David B Thomasb

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.


    Abstract
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background The aim of the present study is to describe the temporal trends in mortality rates of cervical cancer in Shandong Province, China, and to elucidate their likely explanations.

Methods Three retrospective surveys of all causes of death in 1970–1974, 1985–1989 and 1990–1992 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 (30–54 years) than in older women (55–69 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


    Introduction
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
In Shandong Province, China, cervical cancer ranked first as a cause of death due to cancer in women between 1970 and 1974.1 By 1980, however, a declining trend in mortality rates of cervical cancer with time was observed in two areas of Shandong Province. This study was conducted to determine whether this apparent decrease in rates actually occurred, to determine whether this is a cohort or cross-sectional phenomenon, and to identify possible reasons for this apparent decline.


    Materials and Methods
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Three surveys of death certificates from 1970–1974, 1985–1989 and 1990–1992 were conducted in Shandong Province (Table 1Go). The first survey covered a population of 107 792 800, which was about 33.29% of the population of the province. The second survey covered three cities, Jinan, Qingtao, Zibo, and 20 rural counties. It covered a population of 37 625 130, which is about 10% of the population of the province. The third survey covered a population of 16 351 826, about 7% of the total and included two cities, Qingtao and Zibo, and 18 rural counties. The first and third surveys were parts of a death survey of the whole country.1,2 The first death survey included all of the villages in 10 eastern counties plus one-fifth of the villages in the remaining rural counties and one-fifth of the streets in cities, selected at random. All residents in the selected units were included. For the second and third death surveys all cities and counties were stratified on the basis of total cancer mortality rates from the first survey into high-, middle-, and low-areas, and 10% of the total population of all cities and counties were randomly selected from each of those strata. The counties and cities shown in Table 1Go as not surveyed were not included due to lack of local resources. The study design of the three surveys was the same. A handbook was written by four epidemiologists, including one of the authors (Hai-xiu Xu), and published by the Office of China Tumor Prevention and Treatment in Beijing for use by the local government officers who organized and conducted training classes for all study workers to ensure consistency in data collection. A current census of all sampled areas was taken by census workers. Then local medical practitioners in rural areas and in regional hospitals collected information from heads of households and medical records retained by the family on all those who died during the period covered by the survey. Information was collected on place of residence, age, sex, date of birth, date of diagnosis, date of death, and primary site if the death was due to cancer. A 5% sample of all deaths was validated from hospital records. Causes of death were classified according to the Ninth Revision of the International Classification of Diseases.3 Census information was provided by the public safety bureau in each area. The data available included the total numbers of individuals in the population in each 5-year age group and for each sex during each year. Age-adjusted mortality rates were calculated using the world population of 1966 as a standard.


View this table:
[in this window]
[in a new window]
 
Table 1 Mortality rates of cervical cancer per 100 000 women in three time periods in surveyed areas of Shandong Province
 
In addition, data on cervical cancer deaths 1970–1994 were available for Qixia, which is a rural county located in the eastern part of Shandong with a total population of 650 000 in 1994. After an initial death survey of the whole province during 1970–1974, a registry of all deaths in this county was established in 1975, with the support of the Shandong Academy of Medical Sciences. In the first death survey, stomach cancer mortality was found to be very high in Qixia County, and a tumour research station was set up by the county health bureau. When a person dies a death card is filled out by a doctor and sent to the tumour research station. Based on data from these cards, age-specific death rates of cervical cancer were calculated for five time periods, 1970–1974, 1975–1979, 1980–1984, 1985–1989 and 1990–1994. Calculations of death rates by birth cohort were based on these age- and time-specific mortality rates. The effects of age-, time- and cohort-related factors on the trend of mortality of cervical cancer was analysed using a descriptive age-period-cohort model developed by Frost,4 and Kupper's5 quantitative method of age-period-cohort analysis.

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 1986–1992 and rates of syphilis 1954–1960 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 30–54 and 55–69 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.


    Results
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The diagnoses of cervical cancer during the three time periods shown in Table 1Go were made by cytology in 54.5%, 39.0% and 34.45% of the women, respectively; by pathology in 48.96%, 54.7% and 61.55% of the women, respectively, and only by clinical signs and symptoms in 0.53%, 6.30% and 4.00% of the women.

The mortality for cervical cancer per 100 000 women, adjusted to the world population, was 5.57 during 1985–1989, compared with 21.11 during 1970–1974, which is a 73.1% reduction. The mortality for cervical cancer was 4.40 during 1990–1992, which is a 79.1% reduction compared with that of 1970–1974.

The mortality rates for each year during 1970–1974 and 1985–1992 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 1970–1974.

The age-specific mortality rates of cervical cancer in Shandong Province during the three time periods are shown in Table 2Go. The age-specific rates for women over 35 decreased over time. The rates for younger women tended not to decline from 1985–1989 to 1990–1992.


View this table:
[in this window]
[in a new window]
 
Table 2 Age-specific cervical cancer mortality rates during three time periods in Shandong Province
 
Based on the data for Qixia County shown in Table 3Go, the results of a descriptive age-period-cohort analysis are shown in Figure 1Go. Some of the cells in Table 3Go are based on small numbers of observations, and the corresponding rates are unstable. None the less it can be seen in Figure 1Go that mortality rates tended to decline in succeeding birth cohorts, with considerably higher mortality rates from the disease for birth cohorts born before 1925 than for birth cohorts after 1930, and the decline in rates over time was primarily in the former cohorts.


View this table:
[in this window]
[in a new window]
 
Table 3 Age-specific mortality rates of cervical cancer in five time periods in Qixia County, Shandong Province
 


View larger version (32K):
[in this window]
[in a new window]
 
Figure 1 Trends of mortality rates of cervical cancer for birth cohorts in Qixia County, Shandong, China

 
As shown in Table 4Go the odds ratio for succeeding birth cohorts declined from 1892 to 1922 and then changed little in the birth cohorts from 1927 to 1957. As expected, risk increased markedly with age, regardless of birth cohort. After taking into account birth cohort there was little period effect.


View this table:
[in this window]
[in a new window]
 
Table 4 Estimated values of three factors in age-period-chort analysis for cervical cancer in Qixia County (period: from 1970–1974 to 1990–1994; age: from 30–34 to 75–79 years)
 
The prevalence of positive serological tests for syphilis6 are shown in Table 5Go. The data for 1954 to 1957 are for tested high-risk people and the data for the latter 3 years are from screening surveys in the general population. Although data from these two sources are not strictly comparable, both show a marked decline in syphilis rates over time. The correlation coefficient between cervical mortality from 1986 to 1992 in Shandong Province and rates of positive tests for syphilis was significant (r = 0.833, P < 0.05, two-tailed).


View this table:
[in this window]
[in a new window]
 
Table 5 The rates of tested positive serum syphilis 1954–1960 in Shandong
 
Data in the cross-sectional study were collected on 768 women who lived in Jinan and 2121 women who lived in 12 villages. The city group consisted of 643 women aged 30–54 years and 125 women aged 55–69 years; and 1736 and 385 women from the rural areas were also in these two age groups. The percentages of women with selected risk factors in the two age groups in the city and rural areas are shown Table 6Go. Compared with older women, those in the younger age group in both the city and rural areas had a higher level of education, were married at a later age, and had fewer children. More of younger women also had used a intrauterine device (IUD), oral contraceptives and condoms for contraceptives, and fewer of them had smoked cigarettes.


View this table:
[in this window]
[in a new window]
 
Table 6 The changed factors for younger (30–54) and older (55–69 years) women in city and rural areas of Shandong
 
From a vital registry system for each family, we randomly sampled 20% of the women who were not screened to determine whether there was a difference in the number of births between the screened and unscreened women. No significant difference was found, suggesting that the screened women were representative of all women in the population.


    Discussion
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
There has been a sharp decline in cervical cancer rates in the past 30 years in many developed countries where rates as low as 5 per 100 000 females have been reported.7–18 In contrast, the disease remains widespread in many developing countries, such as in rural areas of Panama and Brazil.19,20 Our data show a decrease in cervical cancer mortality in the past 25 years. This phenomenon has also been reported for other provinces of China.1,2 A declining trend in cervical cancer incidence in the past 25 years has also been seen in some other Asian countries. However, the decline was most rapid in China, resulting in one of the lowest incidence rates of cervical cancer among Asian countries.7–11 For example, Coleman calculated a recent trend of decline in cervical cancer incidence in Asia, of –58.5% for Shanghai, –20.7% for Hong Kong, and –31.9 for Nagasaki, Japan.21

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 1970–1972.6 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 1975–1979 and 1980–1985,22 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 30–54 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.23–46 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,25,33,36–46 and these viruses are generally accepted as important and probably necessary causal agents for cervical carcinoma.42–46 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.


    References
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
1 Ministry of Health of China. Atlas of Cancer Mortality in the People's Republic of China. Published by China, 1979, pp.47–50.

2 Li LD, Lu FZ, Zhang SW et al. Epidemic distribution of malignant tumor deaths during 1990–1992 in China. J Chin Tumor 1996;18:403–07.

3 World Health Organization. International Classification of Diseases. Ninth Revision. Geneva: WHO, 1976.

4 Frost WH. The age selection of mortality from tuberculosis in successive decades. Am J Hyg 1939;30:91–96.

5 Kupper LL, Janis JM, Karmous A, Greenberg BG. Variance and dissent: statistical age-period-cohort analysis: a review and critique. J Chron Dis 1985;38:811–30.[ISI][Medline]

6 Hygiene Bureau of Shandong: Experience of Preventive Medicine in Shandong Province. Hygiene Bureau of Shandong, 1987, pp.406–07.

7 Waterhouse J, Muir C, Correa P, Powell J. Cancer Incidence in Five Continents. Vol III. IARC Scientific Publication No. 15. Lyon: International Agency for Research on Cancer, 1976.

8 Waterhouse J, Muir CS, Shanmugartnam K, Powell J. Cancer Incidence in Five Continents. Vol V. IARC Scientific Publication No. 42. Lyon: International Agency for Research on Cancer, 1982.

9 Muir CS, Waterhouse J, Mack T, Powell J, Whelan S. Cancer Incidence in Five Continents. Vol VI. IARC Scientific Publication No. 88. Lyon: International Agency for Research on Cancer, 1987.

10 Parkin DM, Muir CS, Whelan SL, Gao YT, Ferlay J, Powell J. Cancer Incidence in Five Continents. Vol VI. IARC Scientific Publication No. 120. Lyon: International Agency for Research on Cancer, 1992.

11 Parkin DM, Muir CS, Whelan SL, Ferlay J, Raymond L, Young J. Cancer Incidence in Five Continents. Vol VII. IARC Scientific Publication No. 143. Lyon: International Agency for Research on Cancer, 1997.

12 Wu LY, Semenya KA, Hardy RE et al. Cancer rate differentials between blacks and whites in three metropolitan areas: a 10-year comparison. J Nat Med Assoc 1998;90:410–16.[ISI][Medline]

13 Sala M, Dosemeci M, Zahm SH. A death certificate-based study of occupation and mortality from reproductive cancers among women in 24 US states. J Occup Environ Med 1998;40:632–39.[ISI][Medline]

14 Igarashi T, Konno R, Sato S et al. A. Characteristics of uterine cancer detected by mass screening. Jap J Cancer Chemo 1998;25:1519–26.

15 Vioque J, Fenollar J. The distribution of cervical cancer mortality in Spain (1981–1986). An ecological study. Med Clin 1995;104:287–92.[ISI]

16 Lamont DW, Symonds RP. Uptake of cervical screening. Br J Cancer 1993;68:824.[ISI][Medline]

17 Straton JA, Holman CD, Edwards BM. Cervical cancer screening in Western Australia in 1992: progress since 1983. Med J Aust 1993;159: 65–71.

18 Aareleid T, Pukkala E, Thomson H et al. Cervical cancer incidence and mortality trends in Finland and Estonia: a screened vs. an unscreened population. Eur J Cancer 1993;29A:745–49.

19 Faggiano F, Partanen T, Kogevinas M et al. Socioeconomic Differences in Cancer Incidence and Mortality. IARC Scientific Publications No. 138. Lyon: International Agency for Research on Cancer, 1997, pp.65–176.

20 Franco EL, Filho NC, Villa LL et al. Correlation patterns of cancer relative frequencies with some socio economic and demographic indicators in Brazil: an ecologic study. Int J Cancer 1988;41:24–29.[ISI][Medline]

21 Coleman MP, Esteve J, Damiecki P, Arslan A, Renard H. World Health Organization International Agency for Research on Cancer. Trends in Cancer Incidence and Mortality. IARC Scientific Publications No. 121. Lyon: International Agency for Research on Cancer, 1993, pp.42–446.

22 Li HQ, Jin SK, Wu F et al. A method of survival analysis for patients with cervical cancer in Cangshan county, Shandong. Chin J Health Stat 1993;10:29.

23 Slattery ML, Overall JC Jr, Abbott TM et al. Sexual activity, contraception, genital infections, and cervical cancer: support for a sexually transmitted disease hypothesis. Am J Epidemiol 1989;130:248–58.[Abstract]

24 Peng HQ, Liu SL, Mann V et al. Human papilloma virus types 16 and 33, herpes simples virus type 2 and other risk factors for cervical cancer in Sichuan province, China. Int J Cancer 1991;7:711–16.

25 Donnan SPB, Wong FWS, Ho SC et al. Reproductive and sexual risk factors and Human papilloma virus infection in cervical cancer among Hong Kong Chinese. Int J Epidemiol 1989;18:32–36.[Abstract]

26 de Sanjose S, Bosch FX, Munoz N et al. Socioeconomic differences in cervical cancer: two case-control studies in Colombia and Spain. Am J Public Health 1996;86:1532–38.[Abstract]

27 Thomas DB, Ray RM, Pardthaisong T et al. Prostitution, condom use, and invasive squamous cell cervical cancer in Thailand. Am J Epidemiol 1996;143:779–86.[Abstract]

28 Sanchez-Vega JT, Torres ME, Tay-Zavala J et al. Frequency of intraepithelial neoplasia of the cervix and risk factors in women in Mexico City. Ginecol Obstet Mex 1997;65:3–7.[Medline]

29 Biswas LN, Manna B, Maiti PK et al. Sexual risk factors for cervical cancer among rural Indian women: a case-control study. Int J Epidemiol 1997;26:491–95.[Abstract]

30 Munoz N, Bosch FX. Cervical cancer and human papillomavirus: epidemiological evidence and perspective for prevention. Salud Publica Mex 1997;39:274–82.[ISI][Medline]

31 de Sanjose S, Bosch FX, Munoz N et al. Social Differences in Sexual Behaviour and Cervical Cancer. Lyon: IARC Scientific Publication No. 138. Lyon: International Agency for Research on Cancer, 1997, pp.309–17.

32 Yoo KY, Kang D, Koo HW et al. Risk factors associated with uterine cervical cancer in Korea: a case-control study with special reference to sexual behavior. J Epidemiol 1997;7:117–23.[Medline]

33 Becker TM, Lee F, Daling JR et al. Seroprevalence of and risk factors for antibodies to herpes simplex viruses, hepatitis B, and hepatitis C among southwestern Hispanic and non-Hispanic white women. Sex Transm Dis 1996;23:138–44.[ISI][Medline]

34 Daling JR, Madeleine MM, McKnight B et al. The relationship of human Papillomavirus-related cervical tumors to cigarette smoking, oral contraceptive use, and prior herpes simplex virus type 2 infection. Cancer Epidemiol Biomark Prev 1996;5:541–48.[Abstract]

35 Gomes C, Dias M, Falcao F et al. Serologic profile of some sexually transmitted diseases in women with squamous intraepithelial lesions. Eur J Gynaecol Oncol 1998;19:135–37.[ISI][Medline]

36 Chichareon S, Herrero R, Munoz N et al. Risk factors for cervical cancer in Thailand: a case-control study. J Natl Cancer Inst 1998;90:50–57.[Abstract/Free Full Text]

37 Ngelangel C, Munoz N, Bosch FX et al. Causes of cervical cancer in the Philippines: a case-control study. J Natl Cancer Inst 1998;90:43–49.[Abstract/Free Full Text]

38 Svare EI, Kjaer SK, Worm AM et al. Risk factors for HPV infection in women from sexually transmitted disease clinics: comparison between two areas with different cervical cancer incidence. Int J Cancer 1998;75:1–8.[ISI][Medline]

39 Svare EI, Kjaer SK, Smits HL et al. Risk factors for HPV detection in archival Pap smears. A population-based study from Greenland and Denmark. Eur J Cancer 1998;34:1230–34.[ISI][Medline]

40 Han CP, Tsao YP, Sun CA et al. Human Papillomavirus, cytomegalovirus and herpes simplex virus infections for cervical cancer in Taiwan. Cancer Lett 1997;120:217–21.[ISI][Medline]

41 Reyes-Maldonado E, Diaz-Fuente LA, Gonzalez-Bonilla CV et al. Detection of Chlamydia trachomatis by immunofluorescence, Papanicolaou and immunoperoxidase in women with leucorrhea. Rev Latinoam Microbiol 1996;38:65–73.[Medline]

42 Castellsague X, Ghaffari A, Daniel RW et al. Prevalence of penile human Papillomavirus DNA in husbands of women with and without cervical neoplasia: a study in Spain and Colombia. J Infect Dis 1997; 176:353–61.[ISI][Medline]

43 Birley HD. Human Papillomaviruses, cervical cancer and the developing world. Ann Trop Med Parasitol 1995;89:453–63.[ISI][Medline]

44 Matsuura Y, Kawagoe T, Toki N et al. Low grade cervical intraepithelial neoplasia associated with human Papillomavirus infection. Long-term follow-up. Acta Cytol 1998;42:625–30.[ISI][Medline]

45 La Ruche G, You B, Mensah-Ado I et al. Papillomavirus and human immunodeficiency virus infections: relation with cervical dysplasia-neoplasia in African women. Int J Cancer 1998;76:480–86.[ISI][Medline]

46 Ho GY, Burk RD, Klein S et al. Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Natl Cancer Inst 1995;87:1365–71.[Abstract]

47 Schiffman MH. New epidemiology of human papillomavirus infection and cervical neoplasia. J Natl Cancer Inst 1995;87:1345–47.[ISI][Medline]

48 Yang G, Xue HS, He YJ, Ma JM. The results of the behavior risk factors and community environment surveillance related STD/HIV in 8 cities of China. Int Conf AIDS 1998;12:234.

49 Liu H, Xie J, Yu W et al. A study of sexual behavior among rural residents of China. J Acquir Immune Defic Syndr Hum Retrovir 1998; 19:80–88.[ISI][Medline]