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Prevalence and genotype distribution of human papillomavirus: implications for cancer screening and vaccination in Henan province, China

Abstract:

INTRODUCTION:

To provide information for cervical cancer screening and vaccination in Henan province, China, the distribution of human papillomavirus (HPV) was analyzed.

METHODS:

The HPV genotypes were detected using gene array and flow-through hybridization.

RESULTS:

Overall, 38.1% (1,536/4,033) of the women were human papillomavirus deoxyribonucleic acid (HPV DNA) positive. The prevalence of high-risk HPV types was 32.4%. HPV 16 was the most prevalent genotype (8.9%), followed by HPV 52 (5.8%) and HPV 58 (4.4%).

CONCLUSIONS:

The data support close surveillance of women for cervical cancer screening, and HPV prophylactic vaccines including HPV16, HPV 52, and HPV 58 might offer greater protection in this area.

Keywords:
Human papillomavirus; Prevalence; Henan; China.

Cervical cancer is the third most common cancer and fourth leading cause of mortality among women worldwide11. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61:69-90., with more than 85% of the cases occurring in developing countries such as China22. Li J, Huang R, Schmidt JE, Qiao YL. Epidemiological features of human papillomavirus (HPV) infection among women living in Mainland China. Asian Pac J Cancer Prev 2013; 14:4015-4023.. Evidence indicates that a large proportion of cervical cancer can be prevented through organized cervical screening (33. Khorasanizadeh F, Hassanloo J, Khaksar N, Taheri SM, Marzaban M, Rashidi BH, et al. Epidemiology of cervical cancer and human papilloma virus infection among Iranian women - Analyses of national data and systematic review of the literature. Gynecol Oncol 2013; 128:277-281..

Because human papilloma virus (HPV) causes almost all cervical cancers44. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127:2893-2917., human papillomavirus deoxyribonucleic acid (HPV DNA) testing would be appropriate to objectively screen cervical cancer, with high sensitivity and specificity. More than 200 different HPV genotypes have been identified to date, and approximately 40 oncogenic subtypes are associated with the majority of cases of cervical cancer55. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348:518-527.. Based on their association with cervical cancer, HPV genotypes can be classified into high-risk (HR) HPV (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) or low-risk (LR) HPV (HPV 6, 11, 40, 42, 43, and 44)55. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348:518-527.. In particular, HPV 16 and HPV 18 collectively account for 70% of cervical cancers worldwide66. Tracy L, Gaff HD, Burgess C, Sow S, Gravitt PE, Tracy JK. Estimating the impact of human papillomavirus (HPV) vaccination on HPV prevalence and cervical cancer incidence in Mali. Clin Infect Dis 2011; 52:641-645.. To some extent, the detection of HR-HPV may reduce the risk of developing cervical cancer and associated deaths77. Levin CE, Sellors J, Shi JF, Ma L, Qiao YL, Ortendahl J, et al. Cost-effectiveness analysis of cervical cancer prevention based on a rapid human papillomavirus screening test in a high-risk region of China. Int J Cancer 2010; 127:1404-1411., and understanding the HPV genotype distribution would aid with the design of HPV vaccines for cervical cancer prevention.

Here, we investigated cervical HPV infections in the general female population in Henan province, located in central China, to determine the overall and type-specific HPV prevalences, using the commercially available HPV DNA Array.

From January 2014 to August 2014, 4,033 consecutive samples of exfoliated cervical cells from women attending the gynecological outpatient clinic were collected in the First Affiliated Hospital of Zhengzhou University, China. Eligible women included those who were not a virgin, were not presently pregnant, were not presently menstruating, had not had sexual intercourse within seven days, had not undergone a total hysterectomy, had not used vaginal medication in the previous 48 hours, had no history and associated symptoms of other HPV-related diseases, and were willing to undergo HPV testing. All participants agreed to participate in the present study, and the study project was approved by the ethical committee of the First Affiliated Hospital of Zhengzhou University.

Samples of exfoliated cervical cells were collected for HPV genoarray testing according to the manufacturer's instructions (Yaneng Biotechnology Corp., Shenzhen, China). All data were analyzed using Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS Corp., Chicago, IL, USA). The χ2 test was used to assess the statistical significance of any differences in prevalence. A significance level of 0.05 was used.

The median age of the participating women was 40 years (16-87 years). Of the 4,033 samples, no sample was lost, as the control was normal in all tests. Overall, 1,536 (38.1%) women were HPV-positive for any HPV DNA, 32.4% (1,308/4,033) had an HR-HPV infection, which was higher than the 12.6% (510/4,033) that had an LR-HPV infection (Table 1). HPV 16 was the most prevalent genotype (8.9%, 357/4,033), followed by HPV 52 (5.8%, 235/4,033) and HPV 58 (4.4%, 176/4,033) (Table 1). As shown in Figure 1, there were two peaks of HPV infection based on age: the first was for women aged <21 years, of whom 55.6% were infected, and the second was for women aged 66-70 years, of whom 48% were infected (p = 0.003). Similar patterns of two peaks were also observed for HR-HPV infections (p = 0.028) and LR-HPV infections (p < 0.001), with the first peaks for both types of infection for women aged <21 years (48.1% and 29.6%, respectively). However, the second peak for HR-HPV infection was for women aged 56-60 years, of whom 42.5% were infected, and the second peak for LR-HPV infection was for women aged 61-65 years, of whom 25% were infected. The prevalences of multiple types of HPV infections were significantly different among the age groups (p < 0.001), while the prevalences of a single type of HPV infection were relatively constant across the age groups (p = 0.930) (Figure 1). Among the women infected with multiple types of HPV, the first peak (29.6%) was for those aged <21 years old, and the second peak (25.8%) was for those aged 66-70 years (p < 0.001). The prevalence of HPV 16 or HPV 18 did not differ across the age groups (data not shown).

Table 1:
Overall prevalence of human papillomavirus, including specific types and categories (n = 4,033)*.

Figure 1:
Age-specific prevalence of human papillomavirus infection.

A single type of HPV infection was detected in 24.2% (977/4,033) of the entire sample, and multiple types of HPV infections were detected in 13.9% (559/4,033) of the entire sample (Table 2). In the group of women with a single type of infection-, HPV 16 was the most prevalent (18.9%, 185/977), followed by HPV 52 (10.3%, 101/977), HPV 58 (8.1%, 79/977), HPV 53 (6.7%, 65/977), and HPV 6 (5.9%, 58/977). In the group of women with multiple types of infection-, the most prevalent genotype was HPV 16 (30.8%, 172/559), followed by HPV 52 (24%, 134/559), HPV 58 (17.4%, 97/559), HPV 53 (17.2%, 96/559), and HPV 81 (16.1%, 90/559) (Table 2).

Table 2:
Distribution of human papillomavirus infections (n = 4033).

In the present study, the most prevalent HPV genotype was HPV 16, followed by HPV 52 and HPV 58 (Table 1), which was similar to the findings of a previous study of the prevalence of HPV infection in Henan province88. Shen Y, Gong JM, Li YQ, Gong YM, Lei DM, Cheng GM, et al. Epidemiology and genotype distribution of human papillomavirus (HPV) in women of Henan Province, China. Clin Chim Acta 2013; 415:297-301.. However, in another study conducted in this area, the most prevalent HPV genotype was HPV 16 (9.2%, 53/578), followed by HPV 52 (7.8%, 45/578) and HPV 6 (6.9%, 40/578)99. Wang XC, Sun LQ, Ma L, Li HX, Wang XL, Wang X, et al. Prevalence and genotype distribution of human papillomavirus among women from Henan, China. Asian Pac J Cancer Prev 2014; 15:7333-7336.. As the biggest hospital in the center of China, clinical data from the First Affiliated Hospital of Zhenghou University might be more representative of the population. In other areas, such as in the North1010. Hou R, Xu C, Zhang S, Wu M, Zhang W. Distribution of human papillomavirus genotype and cervical neoplasia among women with abnormal cytology in Beijing, China. Int J Gynaecol Obstet 2012; 119:257-261., South1111. Wang YY, Li L, Wei S, Peng J, Yuan SX, Xie JS, et al. human papillomavirus (HPV) infection in women participating in cervical cancer screening from 2006 to 2010 in Shenzhen City, South China. Asian Pac J Cancer Prev 2013; 14:7483-7487., and Southeast1212. Ye J, Cheng X, Chen X, Ye F, Lu W, Xie X. Prevalence and risk profile of cervical human papillomavirus infection in Zhejiang Province, southeast China: a population-based study. Virol J 2010; 7:66.) of China, the most commonly detected HPV types were also different. These differences may be due to the geographical and biological interplay between HPV types or variants and host immunogenic factors, as previously described1313. Xue Y, Zhang W, Chen M, Han L, Luo M. "U" shape of age-specific prevalence of high-risk human papillomavirus infection in women attending hospitals in Shanghai, China. Eur J Obstet Gynecol Reprod Biol 2009; 145:214-218..

Compared with Shenzhen and Shanghai City (13.8% and 30.2%, respectively)1111. Wang YY, Li L, Wei S, Peng J, Yuan SX, Xie JS, et al. human papillomavirus (HPV) infection in women participating in cervical cancer screening from 2006 to 2010 in Shenzhen City, South China. Asian Pac J Cancer Prev 2013; 14:7483-7487.) (1313. Xue Y, Zhang W, Chen M, Han L, Luo M. "U" shape of age-specific prevalence of high-risk human papillomavirus infection in women attending hospitals in Shanghai, China. Eur J Obstet Gynecol Reprod Biol 2009; 145:214-218., a higher (38.1%) prevalence of HPV infection was observed in the present study. The first peak of HPV infection occurred for women aged <21 years (55.6%), which might be related with a lack of adaptive immune responses and susceptibility to HPV infection1212. Ye J, Cheng X, Chen X, Ye F, Lu W, Xie X. Prevalence and risk profile of cervical human papillomavirus infection in Zhejiang Province, southeast China: a population-based study. Virol J 2010; 7:66.. The second peak was observed for women aged 66-70 years (48.4%); this age group also had the most cervical cancer patients (data not shown). It is possible that latent HPV in the body was reactivated owing to physiologic and immunologic dysregulation caused by hormonal fluctuations during the transition to menopause1313. Xue Y, Zhang W, Chen M, Han L, Luo M. "U" shape of age-specific prevalence of high-risk human papillomavirus infection in women attending hospitals in Shanghai, China. Eur J Obstet Gynecol Reprod Biol 2009; 145:214-218. (Figure 1). However, the reasons for the decrease in HPV infection prevalence in women aged >70 years requires further investigation.

Most HPV infections are transient and might resolve spontaneously; however, persistent infections with a subset of HPV genotypes are necessary to develop cervical cancer and its precursors. In the present study, the different peaks of HPV infection were observed in those aged 50-70 years; therefore, women who are first infected with HR-HPV at 56-60 years of age and do not receive appropriate treatment might become infected with LR-HPV at 61-65 years and finally develop multiple types of HPV infection at 66-70 years (Figure 1). When compared with women with a single infection, women infected with multiple types of HPV are at a significantly higher risk of both cervical intraepithelial neoplasia grade 2 and high-grade squamous intraepithelial lesions1414. Dickson EL, Vogel RI, Geller MA, Downs Jr LS. Cervical cytology and multiple type HPV infection: a study of 8182 women ages 31-65. Gynecol Oncol 2014; 133:405-408.. Unfortunately, in the present study, cervical cytology and cancer state were missing for the samples. Therefore, further analysis is needed.

HPV vaccination could decrease the incidence of HPV-related cancers, as well as reduce the burden associated with the treatment of HPV-related benign lesions1515. Goldie SJ, O'Shea M, Campos NG, Diaz M, Sweet S, Kim SY. Health and economic outcomes of HPV 16,18 vaccination in 72 GAVI-eligible countries. Vaccine 2008; 26:4080-4093.. Our findings indicate that the trivalent vaccine (targeted at HPV 16, HPV 52, and HPV 58) would provide good efficacy in the central area of China, because the three most prevalent HPV genotypes in this area were HPV 16, HPV 52, and HPV 58 (Table 1).

In summary, increasing women's awareness of the relationship between HPV infection and cervical cancer is the most important recommendation. The prevalence of HPV infection in the central area of China was 38.1%, and the most common genotypes were HPV 16 (18.9%), HPV 52 (10.3%), and HPV 58 (8.1%). Our data support close surveillance of women aged <21 years or >55 years for cervical cancer screening. Furthermore, our findings support the hypothesis that the next-generation HPV prophylactic vaccines that include HPV 52 and HPV 58 might offer greater protection for women in this area.

ACKNOWLEDGMENTS

The authors are grateful to Doctor Wen-Wen Wang from Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, and associate professor Zhi-Guang Ping from the School of Public Heath, Zhengzhou University, Zhengzhou, China for their assstances during this study.

  • 1
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61:69-90.
  • 2
    Li J, Huang R, Schmidt JE, Qiao YL. Epidemiological features of human papillomavirus (HPV) infection among women living in Mainland China. Asian Pac J Cancer Prev 2013; 14:4015-4023.
  • 3
    Khorasanizadeh F, Hassanloo J, Khaksar N, Taheri SM, Marzaban M, Rashidi BH, et al. Epidemiology of cervical cancer and human papilloma virus infection among Iranian women - Analyses of national data and systematic review of the literature. Gynecol Oncol 2013; 128:277-281.
  • 4
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127:2893-2917.
  • 5
    Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348:518-527.
  • 6
    Tracy L, Gaff HD, Burgess C, Sow S, Gravitt PE, Tracy JK. Estimating the impact of human papillomavirus (HPV) vaccination on HPV prevalence and cervical cancer incidence in Mali. Clin Infect Dis 2011; 52:641-645.
  • 7
    Levin CE, Sellors J, Shi JF, Ma L, Qiao YL, Ortendahl J, et al. Cost-effectiveness analysis of cervical cancer prevention based on a rapid human papillomavirus screening test in a high-risk region of China. Int J Cancer 2010; 127:1404-1411.
  • 8
    Shen Y, Gong JM, Li YQ, Gong YM, Lei DM, Cheng GM, et al. Epidemiology and genotype distribution of human papillomavirus (HPV) in women of Henan Province, China. Clin Chim Acta 2013; 415:297-301.
  • 9
    Wang XC, Sun LQ, Ma L, Li HX, Wang XL, Wang X, et al. Prevalence and genotype distribution of human papillomavirus among women from Henan, China. Asian Pac J Cancer Prev 2014; 15:7333-7336.
  • 10
    Hou R, Xu C, Zhang S, Wu M, Zhang W. Distribution of human papillomavirus genotype and cervical neoplasia among women with abnormal cytology in Beijing, China. Int J Gynaecol Obstet 2012; 119:257-261.
  • 11
    Wang YY, Li L, Wei S, Peng J, Yuan SX, Xie JS, et al. human papillomavirus (HPV) infection in women participating in cervical cancer screening from 2006 to 2010 in Shenzhen City, South China. Asian Pac J Cancer Prev 2013; 14:7483-7487.
  • 12
    Ye J, Cheng X, Chen X, Ye F, Lu W, Xie X. Prevalence and risk profile of cervical human papillomavirus infection in Zhejiang Province, southeast China: a population-based study. Virol J 2010; 7:66.
  • 13
    Xue Y, Zhang W, Chen M, Han L, Luo M. "U" shape of age-specific prevalence of high-risk human papillomavirus infection in women attending hospitals in Shanghai, China. Eur J Obstet Gynecol Reprod Biol 2009; 145:214-218.
  • 14
    Dickson EL, Vogel RI, Geller MA, Downs Jr LS. Cervical cytology and multiple type HPV infection: a study of 8182 women ages 31-65. Gynecol Oncol 2014; 133:405-408.
  • 15
    Goldie SJ, O'Shea M, Campos NG, Diaz M, Sweet S, Kim SY. Health and economic outcomes of HPV 16,18 vaccination in 72 GAVI-eligible countries. Vaccine 2008; 26:4080-4093.
  • This study was supported by the National Natural Science Foundation of China (grant number 81501715), the Youth Innovation Fund of the First Affiliated Hospital of Zhengzhou University, China (grant number 2014001-042) and the Key Project on Science and Technology Research of Henan Province, China (grant number 152102410067; grant number 2013A310622).

Publication Dates

  • Publication in this collection
    Mar-Apr 2016

History

  • Received
    13 June 2015
  • Accepted
    17 Aug 2015
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