Prevalence, genotype distribution and risk factors of cervical HPV infection in Yangqu, China: a population-based survey of 10086 women

ABSTRACT

Human papillomavirus(HPV) infection is a necessary factor for the development of cervical cancer. The HPV vaccine is currently available, but there is still a lack of large-scale research on the distribution and risk factors of HPV. The aim of this study is to investigate the genotype distribution and risk factors of HPV infection in Yangqu which is located in North China. This study enrolled 10086 women aged <65 years from Yangqu County. HPV genotypes were identified via standard HPV DNA testing. The overall prevalence of HPV infection was 8.92%. The prevalence of high-risk HPV types was 8.80%, and it was 0.38% for low-risk HPV types. Single genotype infection accounted for 67.91% in HPV-positive cases. The most common HPV genotypes were HPV-16, −52, and −58. HPV-18 was only the 11th most common type in HPV-positive cases. Women ≥50 years of age had the highest prevalence rate of HPV, and women <30 years had the lowest prevalence rate. The distribution of HPV genotypes also varied among the three age groups: <30, 30–49, and ≥50 years. The risk factors that contributed to the rate of HPV infection included low educational level, low income, smoking, age at first sexual encounter <23 years old, and number of births ≥3 times. This large routine clinical practice report of HPV prevalence and genotype distribution revealed the characteristics of HPV infection-type distributions in Shanxi Province, which should be considered in formulating comprehensive prevention strategies including vaccination for cervical cancer in China.

KEYWORDS:

• Cervical cancer screening
• human papillomavirus
• genotyping
• prevalence
• risk factors
• China

Introduction

Cervical cancer is one of the major malignant tumors threatening women all over the world. According to statistics, there are 527,600 cases of cervical cancer in the world, including 265,700 cases of death caused by cervical cancer.¹ Human papillomavirus (HPV) causes many cancers including oro-pharyngeal, vulvar, vaginal, anal, and penile and so on, but the cervical cancer is the “classic” cancer of HPV. Persistent infection of high-risk human papillomavirus (HR-HPV) is a necessary factor for the occurrence of cervical cancer, but its characteristic is that the infection rate and type are different in different regions.^2,3 At present, there is no report of HPV infection in this region in Shanxi Province.

In the post-vaccine era, how to formulate different vaccine intervention measures to prevent and control cervical cancer effectively according to the characteristics of different regions is the focus of scholars. China has approved bivalent (2vHPV preventing infection from HPV16 and 18 genotypes), quadrivalent (4vHPV from HPV6, 11, 16, and 18 genotypes) and 9-valent (9vHPV from HPV6, 11, 16, 18, 31, 33, 45, 52, and 58 genotypes) vaccines,with 9vHPV being the successor to the others. Existing studies have shown that the distribution of HPV genotypes varies with different regions. In the global scope, the top 10 are HPV16, 18, 58, 52, 51, 31, 56, 33, 45 and 53 in order. The top 5 places by region are: Africa HPV16, 18, 58, 52, 51;Central/South America HPV16, 18, 61, 71, 58;North America HPV16, 53, 52, 18, 39; Asia HPV16, 52, 58, 18, 56;Europe HPV16, 18, 31, 33, 58. But the Asian population reported here includes fewer Chinese women. China has vast territory and abundant resources, different populations also have different characteristics of HPV infection. Shanxi has a large region and a wide area, but the study on the characteristics of HPV infection in this region is limited, especially the study on the regional factors of HPV infection in China or our province is very few at present. This study intends to clarify the characteristics of HPV distribution in this region and target the key infected population according to analyze the prevalence of HPV, the distribution characteristics of HPV genotypes and the risk factors affecting HR-HPV infection in Yangqu area of Shanxi Province, so as to provide scientific basis for preventing HR-HPV infection through population behavior and vaccine intervention and achieving cervical cancer prevention gateway forward.

Methods

Study population

This survey was based on data obtained from the screening program and the baseline data of an ongoing prospective cohort study (Shanxi CIN Cohort). The rational, design and methods of the Shanxi CIN Cohort Study have been detailed elsewhere.^4,5 Briefly, we organized a free cervical cancer screening program and detected HPV infection for 10086 eligible women permanently residing in Yangqu County of Taiyuan city between September and December of 2014. All participants provided their signed informed consent prior to enrollment. The inclusion criteria were as follows: (1) sexually active woman;(2) aged <65 years;(3)of the Han ethnic group;(4) with ≥1 year of continuous residence in Yangqu County and (5)willingness to participate in the screening program. The exclusion criteria were as follows: pregnancy, history of other malignant tumors and uterine surgery resection or cervical lesion treatment. We investigated a total of 10086 women with a demographic characteristics-related questionnaire and screened them by taking biological specimens from the cervix (see below) in conjunction with gynecologic examinations. Our study was approved by the ethics committee of the Second Hospital, Shanxi Medical University (Figure 1).

Figure 1. Study population

Data collection

Demographic information

In-person interviews were conducted by trained and qualified investigators face-to-face using a unified, structured demographic characteristics-related questionnaire. The demographic information included age, number of education years, yearly income, use of tobacco, passive smoking, reproductive patterns (including menopause, gravidity, number of birth, use of tubal ligation for contraception and age at first sexual intercourse), and history of gynecological events.

Biological specimens

It was forbidden to apply vaginal douching or to have sexual intercourse 48 hours prior to the gynecological examination for each subject. After the cervix was exposed, the HPV testing brush was fully placed into the cervical canal and gently rotated 3–5 times. The exfoliated cervical epithelial cells then adhere to the flat sides of the bristles.The tip of the cervix brush is then placed into a vial containing transport medium. Then, the sample was stored at −20°C and was processed for HPV genotyping within 2 weeks.

Clinical laboratory tests

HPV genotyping by HybriMax was performed using an HPV GenoArray Test Kit (HybriBio Ltd, Chaozhou, China) with the residual Pap test specimens. This assay can identify 21 types of HPV, including 15 high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) and six low-risk types (6, 11, 42, 43, 44 and CP8304) by the flow-through hybridization technique using a TC-96/G/H6 HPV DNA Amplification Analyzer and an HMM-2 fast nucleic acid molecule hybridization instrument (HybriBio Ltd).

Statistical analysis

We performed a double-pass entry of all the data using EpiData 3.1 software (Jens M Lauritsen, Odense, Syddan Mark, Denmark). The descriptive statistics were used to describe the frequency and proportion and the mean and standard deviation (SD) of the demographic characteristics.

For comparisons among different age groups, the categorical variables were compared by using the Pearson χ2 test, and a post hoc analysis was examined using Bonferroni’s method. The factors related to HR-HPV infection were analyzed using the nonconditional logistic regression model for multivariate analysis, using a stepwise screening method. All the reported P values were made on the basis of two-sided tests with a significance level of 0.05. The statistical analyses were performed using SPSS 19.0 statistical package for Windows (SPSS Inc., Chicago, IL, USA).

Results

Distribution characteristics of HR-HPV infections

Overall HPV prevalence

The overall detectable HPV infection rate was 8.92% (900/10086) in this screening sample, with 8.80% (888/10086) positive for one or more HR-HPV and 0.38% (38/10086) positive for one or more LR-HPV.

In all these 10086 subjects, the highest overall prevalence of HPV was found in women ≥50 years old (328/3114, 10.53%), while the lowest HPV prevalence was found in women <30 years old (44/603, 7.30%). The overall HPV prevalence in women 30–49 years was 8.29% (528/6369). The difference was statistically significant among the different age groups (Table 1). The rates for different HR-HPV types were also altered among the three age groups. The same results occurred with overall prevalence; the HR-HPV prevalence was the highest in women ≥50 years (10.24%), and the lowest rate was found in women <30 years of age (7.30%). At the same time, the LR-HPV positive rate was 0%, 0.28% and 0.64% in the three age groups (<30 years, 30–49 years, and ≥50 years, respectively).

Table 1. Comparison of HPV infection rates among different age groups (%).

Age groups	N	No. positive cases	Prevalence (%)	P	No. positive cases for LR-HPV	Prevalence (%)	P
<30 y	603	44	7.30^a	0.001	0	0^d	<0.001
30–49 y	6369	528	8.29^b		16	0.28^e
≥50 y	3114	328	10.53^c		20	0.64^f

There were significant differences among the different age groups according to Bonferroni’s multiple comparisons (α’ = α/C₃² = 0.0167).

HPV genotype distribution

Table 2 shows the distribution of HR-HPV subtypes in all the tested women. The most commonly detected HR-HPV type were HPV-16, HPV-52, and HPV-58. Meanwhile, when considering the prevalence of these genotypes in the different age groups (<30 years, 30–49 years, and ≥50 years), the HR-HPV genotype distributions were different as well (Table 2). The five most common HR-HPV genotypes in women who were 30–49 years old were HPV-16, −52, −58, −56, and −66. The five most common HR-HPV types in women ≥50 years, in decreasing order, were HPV-16, −52, HPV-58, −53, and −66. The two most common HR-HPV types were the same (HPV-16 and −52) in these two older age groups, while the same two HPV types were also the most common in younger women <30 years old; HPV-16 was still the most common genotypes in the younger group. The next most common HPV genotypes in women <30 years were HPV-53, −68, and −33. The three least frequently detected HR-HPV genotypes were HPV-35, −45, and −59 (Table 2).

Table 2. HPV prevalence and genotype distribution.

	All ages Overall total cases n = 10086			<30 y n = 603			30–49 y n = 6369			No. Positive cases
	Genotypes	No. Positive cases	Prevalence (%)	Genotypes	No. Positive cases	Prevalence (%)	Genotypes	No. Positive cases	Prevalence (%)	Genotypes	No. Positive cases	Prevalence (%)
HR-HPV types	16	345	3.42	16	11	1.82	16	204	3.20	16	130	4.17
	52	179	1.77	52	9	1.49	52	107	1.68	52	63	2.02
	58	148	1.47	53	5	0.83	58	90	1.41	58	55	1.77
	53	77	0.76	68	5	0.83	56	41	0.64	53	37	1.19
	66	74	0.73	33	4	0.66	66	40	0.63	66	30	0.96
	56	73	0.72	51	4	0.66	31	35	0.55	56	28	0.90
	51	61	0.60	56	4	0.66	53	35	0.55	51	26	0.83
	33	58	0.58	66	4	0.66	33	32	0.50	33	22	0.71
	31	52	0.52	31	3	0.50	51	31	0.49	68	18	0.58
	68	52	0.52	58	3	0.50	68	29	0.46	18	17	0.55
	18	38	0.38	39	2	0.33	39	22	0.35	31	14	0.45
	39	35	0.35	59	2	0.33	18	20	0.31	39	11	0.35
	35	30	0.30	18	1	0.17	35	20	0.31	59	11	0.35
	59	29	0.29	35	0	0.00	59	16	0.25	35	10	0.32
	45	5	0.05	45	0	0.00	45	3	0.05	45	2	0.06
Subtotal-any HPV type		1256			57			725			474
LR-HPV Types	CP8304	20	0.20	CP8304	0	0.00	CP8304	9	0.14	CP8304	11	0.35
	43	11	0.11	6	0	0.00	43	7	0.11	6	7	0.22
	6	8	0.08	11	0	0.00	11	4	0.06	43	4	0.13
	11	6	0.06	42	0	0.00	6	1	0.02	11	2	0.06
	42	0	0.00	43	0	0.00	42	0	0.00	42	0	0.00
	44	0	0.00	44	0	0.00	44	0	0.00	44	0	0.00
Subtotal-any HPV type		45			0			21			24

Distribution of single and multiple HR-HPV infections

When considering the characteristics of co-infection with multiple HR-HPV genotypes, we found that single HR-HPV infections were the most common in the local population, with an overall prevalence of 5.98%, which accounted for 67.91% of all the HR-HPV infectious women. The overall prevalence of multiple HR-HPV types of infection was 2.83%, which accounted for 32.09% of HR-HPV infectious cases, and with the increase of age, the percentage of multiple infections in the same age group gradually increased, which were 22.73%, 31.62% and 34.17%, respectively. Two HPV genotypes (double infection) were the most common in multiple HR-HPV infection distributions, with an overall rate of 1.99% (Table 3). Three HPV genotypes (triple infection) and four or more detectable HR-HPV genotypes were the next most common, with an overall prevalence of 0.58% and 0.26%, respectively.

Table 3. Distribution of single and multiple HR-HPV infections (n = 888).

	All ages Overall total cases n = 888			<30y n = 44			30–49y n = 525			≥50y n = 319
HR-HPV Infections	HR-HPV positive cases	Percentage (x/888) (%)	Prevalence (x/10086) (%)	HR-HPV positive cases	Percentage (x/44) (%)	Prevalence (x/10086) (%)	HR-HPV positive cases	Percentage (x/525) (%)	Prevalence (x/10086) (%)	HR-HPV positive cases	Percentage (x/319) (%)	Prevalence (x/10086) (%)
Single HPV type	603	67.91	5.98	34	77.27	0.34	359	68.38	3.56	210	65.83	2.08
Two HPV types	201	22.64	1.99	8	18.18	0.08	124	23.62	1.23	69	21.63	0.68
Three HPV types	58	6.53	0.58	1	2.27	0.01	31	5.9	0.31	26	8.15	0.26
≥Four HPV types	26	2.93	0.26	1	2.27	0.01	11	2.1	0.11	14	4.39	0.14
Total	888	100.00	8.80	44	100.00	0.44	525	100.00	5.21	319	100.00	3.16

Abbreviations: HPV, human papillomavirus; HR-HPV, high-risk HPV.

Analysis of the potential risk factors for HR-HPV infection

Associated factors with HR-HPV infection in the univariate analysis between the study group (HR-HPV positive) and the control group were as follows: age, education level, annual income, smoking history, spouse smoking history, menopause status, age at first intercourse, gravidity, number of birth, use of tubal ligation for contraception, and gynecologic surgery history (Table 4).

Table 4. Univariate analysis of the potential risk factors for HR-HPV infection (n = 10086).

Variable	HR-HPV negative (n = 9198)	HR-HPV positive (n = 888)	χ^2	P
Age (years)			12.245	0.002
<30	559	44
30–49	5844	525
≥50	2795	319
Education level			6.364	0.041
Primary school or below	1367	151
Junior middle school	4480	448
Senior middle school orabove	3351	289
Annual income			8.769	0.012
<10000 CNY	1028	912
10000–30000 CNY	6153	5628
≥30000 CNY	2905	2658
Smoking history			14.177	0.001
No	9126	870
Yes	72	18
Spouse smoking history			6.227	0.014
No	4276	374
Yes	4922	514
Menopause or not			14.783	<0.001
No	6834	607
Yes	2364	281
Age at first intercourse			10.697	0.001
<23 years old	3737	411
≥23 years old	5461	477
Gravidity			6.963	0.008
<3 times	4393	383
≥3 times	4805	505
Parity			12.819	<0.001
<3 times	7712	703
≥3 times	1486	185
Use of tubal ligation for contraception			9.009	0.003
No	7799	719
Yes	1399	169
Gynecologic surgery history			88.473	<0.001
No	8244	703
Yes	954	185

The multivariate analysis suggested that education level, annual income, smoking history, age at first intercourse, and number of birth were independently associated with HR-HPV infection (Table 5). The regression equation was logit P = −1.103–0.333 × _2–0.233 × ₃ + 0.813 X_{4 –} 0.179 × ₇ + 0.205 X₉. Education level and annual income were protective factors for HR-HPV infection. For each 1-grade increase in education level, the risk of HR-HPV infection was reduced by 28.4%. For each 1-grade increase in annual income, the risk of HR-HPV infection was reduced by 20.8%. The HR-HPV infection risk in female smokers was 2.254 times greater than that of nonsmokers. Women whose age at first intercourse was less than 23 years old had the highest risk of HR-HPV infection. The risk in women whose age at first intercourse was more than 23 years old was 83.6% of that in women whose age at first intercourse was less than 23 years old. The HR-HPV infection risk in women with number of birth ≥3 times was 1.228 times greater than that of women with number of birth <3 times. Accordingly, the multivariate analysis showed that low educational level, low income, smoking, age at first intercourse <23 years old, and number of birth ≥3 times were potential risk factors for infection with HR-HPV (Table 5).

Table 5. Results of multivariate analysis of the potential risk factors for HR-HPV infection (n = 10086).

Variable	β	S.E.	Wald	OR (95%CI)	P
Education level
Primary school or below				1.00
Junior middle school	−0.333	0.059	31.472	0.716(0.638 ~ 0.805)	<0.001
Senior middle school or above	−0.333	0.059	31.472	0.716(0.638 ~ 0.805)	<0.001
Annual income
<10000 CNY				1.00
10000–30000 CNY	−0.233	0.063	13.889	0.792 (0.700 ~ 0.895)	<0.001
≥30000 CNY	−0.233	0.063	13.889	0.792 (0.700 ~ 0.895)	<0.001
Smoking history
No				1.00
Yes	0.813	0.295	7.581	2.254 (1.264 ~ 4.020)	0.006
Age at first intercourse
<23 years old				1.00
≥23 years old	−0.179	0.076	5.535	0.836 (0.720 ~ 0.971)	0.019
Parity
<3 times				1.00
≥3 times	0.205	0.096	4.535	1.228 (1.016 ~ 1.483)	0.033

Discussion

General background and age characteristics of HPV infected women

This population-based study showed that the overall HPV infection rate of women in Yangqu, Shanxi province, China was 8.92%, and the total positive rate was slightly lower than the worldwide HPV infection rate of 10.4% (95% CI 10.2–10.7). The rate was close to the corresponding estimated Asian region data reported by de Sanjos S⁶ of 8% (7.5–8.4). However, the rate was lower than that of Africa (22.1%), Central America and Mexico (20.4%), and North America (11.3%) and was close to the infection rate of Europe (8.1%).^7–9

This study showed that all the different age groups with HPV had a higher infection rate and were mainly consistent with a high risk of infection. The HR-HPV infection peak in the high risk age group was similar to the result in Qiao YL’s study,¹⁰ but there was no peak that appeared in the younger group. The reason for this result may be as follows. First, the result may attribute to selection bias. Because our study was a free screening that looked deeply into local areas, the 10086 screening participants were concentrated with childbearing ages and older women. Women under 20 years old accounted for only 0.05% (5/10086) of the study population, and women under 25 years old accounted for only 1.50% (151/10086). It has been reported that, because of a frequent sex life and an unsensitized immune system, approximately 16–24 year old women are always susceptible to HPV infection.^11,12 If a high-risk HPV infection is persistent, it is more likely to cause cervical malignant lesions.^13,14 Also, too many sexual partners, a premature sex life, sexual behavior disorders, too many pregnancies, smoking and bad health habits were the main reasons for HPV infection.^4,15–22 Maybe because of this selection bias, which was a small constituent ratio for women less than 25 years old, there was no peak in 16 to 24 year-old young women. Second, due to decreased ovarian function, estrogen levels, and immunological function, as well as the resistance to harmful factors in the world and the ability to clear HPV, women more than 50 years old have more opportunities to acquire an HPV infection.^23–26 At the same time, older women are exposed to risk factors for a longer time, resulting in an increased persistent HPV infection rate. Thus, age is an important factor for HPV infection, and women more than 50 years old are the focus of the local prevention and treatment of cervical cancer. It is of great importance for the prevention and treatment of cervical precancerous lesions and cervical cancer to improve these women’s self-healthcare consciousness and to strengthen their screening. In addition, to understand the characteristics of HPV infection in different age groups also contributes to effective selection of the target population for the application of a preventive vaccine.

Distribution of HPV genotypes

HR-HPV-persistent infection is necessary for cervical cancer and precancerous lesions.²⁷ HPV genotype distributions have regional differences, and the types associated with cervical cancer are not the same.^28–30 Although the detection rate of HPV16 varies according to different countries and areas, it always has a relatively high rate.^31,32 In our study, we used an HPV GenoArray Test Kit (HybriBio Ltd, Chaozhou, China) that had good interassay agreement, with the reference standard Roche Linear Array³³ and hybrid capture II³⁴ for the detection of most HPV genotypes. Except for the two types not detected (42 and 44), the detection rate of HPV16 was still the highest, accounting for 38.33% of the total positive infection (345/900), followed by 52, 58, 53, 66, 56, 51, 33, 31, 68, 18, 39, 35, 59, CP8304, 43, 6, 11, and 45. The top three high-risk HPV types were 16, 52, and 58, which were the same as those reported in several domestic studies.^29,35,36 In this study, 7 high-risk types (HPV16, 18, 31, 33, 45, 52, and 58) and 2 low-risk types (HPV 6 and 11), covered by nine valent HPV vaccines, accounted for 76.9% of all HPV infections, which means that we can prevent 76.9% of HPV infections through vaccination.

Characteristics of single and multiple infections of HPV

In this study, every age group had a higher infection rate of HPV than normal people,³⁷ especially for high-risk HPV infections. The positive infections in this type were mainly single infections. Studies have shown that most of cervical endothelial injuries are caused by single HR-HPV-type infection,³⁶ while the other types of co-infection have little effect because of the dormant infection status for other types of HPV when one primary type of HPV proliferates.^38,39 However, other studies have indicated that Infection with multiple HPV types may increase the risk of abnormal cell proliferation and cervical lesions in women.⁴⁰ Further studies need to be done to clarify it.

Risk factors for HR-HPV infection

Education level and annual income

Education level and annual income were protective factors of HR-HPV infection. The education level of primary school or below had the highest risk of HR-HPV infection. According to different education years (primary school or below, junior middle school, senior middle school or above), the likelihood of HR-HPV infection was reduced by 28.4% for each additional level when other factors were the same. Women whose annual income was less than 1 million were most likely to be infected with HR-HPV, and the possibility of HR-HPV infection was reduced by 20.8% for each additional level. Possibly, those who had a high level of education and good economic foundation always had a better health condition, as well as better health consciousness and health habits, than those who had a low education level and poor economic foundation. Because HPV spreads through feculent sexual life,^39,41 women with a poor economic foundation may be more susceptible to HR-HPV.

Age at first intercourse and number of birth

Women with an age at first intercourse <23 years old and number of birth ≥3 times had the highest risk of HR-HPV infection. The results of this study showed that the risk of HR-HPV infection in the first intercourse age ≥23 years group was only 83.6% of that in the first intercourse age <23 years group. The risk of HR-HPV infection in the number of birth ≥3 times group was 1.228 times greater than that of the number of birth <3 times group. These results are consistent with previous studies,⁴² showing that the age at first sexual intercourse and number of birth were risk factors. The possible reason for this result might be that long lengths of exposure to risk factors for women with earlier sexual behavior and more number of birth led to more serious cervical injury. Our study indicated that women whose age at first intercourse was less than 23 years, and whose number of birth was more than 3 times, should be classified as a key population for the prevention of HR-HPV infection.

Smoking history

Smoking has been recognized as a risk factor for the development of cervical intraepithelial neoplasia,⁴³ but it remains a controversial topic whether smoking increases the risk of HR-HPV infection. This study concluded that smoking is a risk factor for HR-HPV infection, and the risk value was as high as 2.254 times that of nonsmokers, which is consistent with Coker’s study.⁴⁴ Various measures should be taken to achieve good primary prevention and to work toward a smoke-free society, such as a smoking ban for youth, advocating smoking abstinence for middle-aged people, and advising the elderly to smoke less or use harmless cigarettes.

Many studies have shown that the incidence of cervical cancer is closely related to HPV infection, especially a persistent, repeated HR-HPV infection, but the distribution of HPV genotypes varies according to different countries, regions, geographical environments and races.⁴⁵ This is the largest routine clinical practice report of HPV prevalence and genotype distribution in Shanxi Province. But it also has some limitations.The main limitation is that there are no pathological results in these cases.Due to the limited funding of the study, we can not conduct free colposcopy examination on these participants. Secondly, we only detected the expression of 21 HPV genotypes,including 15 high-risk types and 6 low-risk HPV genotypes, which may lead to overestimation of the high-risk HPV genotype in the HPV-positive female participants. Further studies are therefore necessary to confirm these associations. Additionaly, given that our study focuses on cervical cancer, it can not provide a basis for vaccine use in men, and performing similar studies for other HPV cancers, especially oro-pharyngeal cancer in man, would further guide vaccine use.

In this study, the HPV infection rate of the female population in the Yangqu area was high, and the infection rate was increased with age in women who were 20–65 years old. HPV-16 was still the most prevalent HR-HPV type in this population of women, followed by HPV-52 and HPV-58. The overall and age-specific prevalence and genotype distribution of HR-HPV are different in this Chinese population compared to reports from western countries. The characteristics of an HPV infection-type distribution should be considered in formulating comprehensive prevention strategies for cervical cancer in China. According to our study, HPV52 and 58 are the main genotype in Yangqu, China, but not the HPV18. So our epidemiological survey can effectively guide local goverment to develop HPV vaccination programs for targeted vaccination in the Yangqu area in particular. As the incidence of cervical cancer in Shanxi Province is nearly 10 times higher than the national average This region is the worst disaster area for cervical cancer. Therefore, this region should be first covered in the promotion of vaccine in China. Furthermore this policy, especially for use of the vaccine in men, will depend on a molecular epidemiology study of this type in oro-pharyngeal, penile and anal cancers of men.The independent risk factors of HR-HPV infection include the following: education of primary school and below, an annual income <1 million, use of tobacco, age at first sexual encounter <23 years old, and number of birth ≥3 times. Those who have these risk factors are key populations for HR-HPV infection prevention in the Yangqu area, and we should first vaccinate this particular group of people who may be infected.

Conclusions

At the present stage, the bivalent HPV vaccine has been approved in the domestic market; the nine valent vaccine has almost completed clinical trials and will enter clinical application in the near future, benefiting the majority of women. This study provides a basis for exploring the characteristics and risk factors of HR-HPV infection in Shanxi, Yangqu so that we can concentrate on this high risk population in cervical cancer screening. This study provides a reference for further studies on therapeutic vaccine strategies.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Authors’ contributions

MH conceived and designed the research; WW, ZW, YW, WZ, DL, HL, and JY conducted the research; JY analyzed the data; JY, ZW, and JW performed statistical analysis; JY wrote the paper; MH had primary responsibility for final content.

Ethics approval

The study was conducted according to the current ethical standards including the WMA Declaration of Helsinki and was submitted to the appropriate regulatory authorities including ethical committees in Yangqu, as requested by local regulations. This study was approved by the ethics committee of the Second Hospital, Shanxi Medical University and the reference number was 2013002.

Acknowledgments

We are grateful for the contribution of our coworkers involved in conducting the study and writing this article. We thank all the study participants, as well as the investigators and local healthcare workers from Yangqu County Hospital, for their help with the study.

Supplementary material

Supplemental data for this article can be online at http://dx.doi.org/10.1080/21645515.2019.1689743.

Additional information

Funding

This work was supported by the Special Public Welfare Industry Research of National Health and Family Planning Commission of China [grant number 201402010], the National Natural Science Foundation of China [grant number 81972452], the Key Research and Development Plan of Shanxi Province [grant number 201803D31121] and Scientific and Technologial Innovation Programs of Higher Education Institutions in Shanxi [grant number 201804025].