Prevalence of HPV infection among 157,038 Chinese females in Hunan Province, central-south China: Research article

Background: In the present study, we aimed to investigate the human papillomavirus (HPV) infection rate in females of Hunan Province, China, as well as the common HPV genotype distribution. Moreover, we also explored the differences in HPV infections among females of different ages. Methods: Clinical data were collected from 157,038 females who had tested HPV infection in the Third Xiangya Hospital of Central South University from November, 2010 to May, 2017. Results: The overall HPV infection rate was 19.91%.The most commonly detected genotypes were HPV52 (4.62%), HPV16 (3.52%), HPV 58(3.12%), HPVCP8304 (2.91%), and HPV53 (2.06%). The highest infection rate was found in females under the age of 20 (30.33%), the second highest infection rate was found in females over the age of 60 (24.72%), and females aged 30-39 showed the lowest HPV infection rate (18.11%). In addition, 71.32% of the infections were single HPV infections. Among the multiple HPV infections, HPV16/HPV6 co-infection was the most commonly detected combination (0.52%). Conclusions: In this study, we examined the epidemiology of HPV and the prevalence of the common HPV infection in Hunan Province, central-south China. We have revealed the prevalence and distribution of the different HPV types. Our study showed that females under the age of 20 and over the age of 60 were at higher risk of HPV infection than females of other ages. Moreover, our region should make extra efforts to the prevention and treatment of HPV52, HPV16 and HPV58 infections.

Massive current studies have revealed that HPV infections play an important role in the occurrence and development of cervical lesion, especially high-risk HPV infections. 5 Multiple studies have shown that HPV16 and HPV18 are the most commonly detected high-risk HPV genotypes. [6][7][8] However, there are very few studies on the HPV infection in Chinese population. Meanwhile, HPV vaccine has entered the Chinese market. Therefore, in order to provide supportive evidence for public health decisionmaking, it is urgently necessary to launch a large-scale epidemiological study in regards to genotype distribution characteristics of HPV, such as infection rate and genotype distribution.

Statistical analysis
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Data were input into SPSS 23.0 for analysis and expressed as mean ± SD, and was determined by one-way ANOVA. Categorical variables were presented as a rate or composition ratio, and significance was determined with chi-squared test (χ2). A p<0.05 was considered statistically significant.

Results
The overall prevalence of HPV A total of 157,038 females participated in the HPV genotyping program, among which the mean age was 39.20 ±11.06. Data of Table 1 showed that 31,278 females were diagnosed with HPV infection with a mean age of 39.90. Meanwhile, the mean age of HPV-negative females was 39.03. As shown in Among the HPV positive infected females, 71.32% of them were diagnosed with single HPV infection, and the infection rate was 14.20 % (Table 2). Moreover, 24.40% of HPV positive females were diagnosed with double HPV infections, and the infection rate was 4.26%. The infection rate of triple HPV infections was 1.03%. Only 655 females were diagnosed with quadruple or more HPV infections, accounting for 2.09% of the total infected patients, and the HPV infection rate was 0.42%. In the cases of multiple HPV infections, the most commonly detected combination was HPV16/HPV6, followed by HPV52/HPVCP8304, HPV52/HPV58, HPV52/HPV16 and HPV52/HPV53 (Table 3). Table 4, patients were divided into six groups according to age range as follows: <20, 20-29, 30-39, 40-49, 50-59, or ≥ 60 (3,214 patients whose ages were unknown were excluded). The age of group of <20 had the highest rate of HPV infection (30.33%), followed by the age group of ≥ 60 with an HPV infection rate of 24.72%, while the age group of 30-39 had the lowest rate of HPV infection (18.11%). The differences of HPV infection rates among different groups were statistically significant, as well as high-risk HPV infection rates. The age group of <20 had the highest rate of high-risk HPV infection (25.00%), followed by the age group of ≥ 60 (23.01%) and the age group of 30-39 (15.74%).

The distribution of HPV genotypes
The top five HPV genotypes with a high infection rate were HPV52 (4.62%), HPV16 (3.52%), HPV58 (3.12%), HPVCP8304 (2.91%) and HPV53 (2.06%). Table 4, shows that the top three HPV genotypes with a high infection rate in the age group of <20 and the age group of 20-29 were HPV52, HPV16 and HPV58. In contrast, the top three HPV genotypes with a high infection rate in the age groups of 30-39, 40-49 and 50-59 were HPV52, HPV16 and HPV58. In the age group of ≥ 60 years, three HPV genotypes with a high infection rate were HPV16, HPV58 and HPV52.

Discussion
It is difficult to obtain information about HPV prevalence in general population. To better understand the HPV prevalence in general population, researchers speculate the HPV prevalence and the differences among HPV genotypes based on the cervix uteri ThinPrep cytological test. Multiple epidemiological studies worldwide have revealed that the HPV prevalence rate ranges from 6.1% to 33.5% among different regions, and the average rate is around 10%. 9 A large scale meta-analysis with 1 million cases 10 has shown that all of the females are HPV negative in cytologic evaluation.  The national reports on genotypes of HPV are different from overseas studies, which might be attributed to following reasons. 1. The constitution of the study populations are different. Most of the cases in this study were from physical examination center, better representing the general population. 2. The susceptibility of different genotypes of HPV is based on the region or race of patients, indicating that the susceptibility of different genotypes of HPV in Chinese females is different from that of other counties. 3. There are differences in the age of objects in different studies. In our current study, the age the patients ranged from 11 to 96 years. The most commonly detected genotype of HPV in the age group of over 60 was HPV16 instead of HPV52 in this study. However, the objects in most epidemiologic studies are limited within certain age range. Although the bivalent and tetravalent HPV vaccines are currently available in Chinese market, they are likely to be effective for HPV16/18 but not for HPV52/58, which are the most commonly detected HPV genotypes in China. Therefore, the 9-valent HPV vaccine should be introduced into Chinese market, and we should also HPV is a sexually transmitted disease. Sexually active females are more susceptible to HPV, especially the high-risk HPV. Many epidemiologic studies have reported that females under the age of 24 are more susceptible to HPV infection than other ages, with an overall infection rate of 15%. Moreover, the infection rate in females aged of 25-29 is only 10%. However, the infection rate in females over the age of 35 is increased to 24%. 11,15,19 The similar trend has been observed in high-risk HPV infections but not in low-risk HPV infections. With an epidemiologic studies of 20,000 females in Poland and 9,000 females in Costa Rica, the researchers have discovered that the HPV infection rate is higher in relatively young and relatively old females, while females in between these ages have a lower HPV infection rate. 20,21 Similar conclusions are also drawn by the domestic studies. [12][13][14][15] Our study showed that females under the age of 20 had the highest HPV infection rate (30.33%), and the second highest HPV infection rate was observed in females over the age of 60. However, females aged of 30-39 had the lowest HPV infection rate. The similar correlation between age and infection rate was found in the high-risk HPV infections. The high-risk HPV infection rate was 25% in the females under the age of 20, which was 23.01% in the females over the age of 60, and females aged 30-39 had the lowest infection rate of 15.74%. This age-infection rate pattern did not apply to the low-risk HPV infections. There are still some differences among different reports. The possible reason could be attributed to that the age distributions in the populations of studies were different, or the age range sets were different. Moreover, the objects in this study were patients who went to hospital for examination, and they should be different from general population. The higher infection rate in females under the age of 20 or over the age of 60 probably is attributed to following reasons. First, these cases were mainly from gynecological clinic, therefore some selection existed bias existed.
Second, the females at these ages had a relatively low immunity and were susceptible to viral infection. Moreover, there might be a lack of the ideas of regular gynecological examination.

Consent for publication
All the participants consented to their information in this study for publication.

Availability of data and material
All data generated or analyzed during this study are included in this published article and its supplementary information files.

Competing interests
The authors declare that they have no competing interests.