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Year : 2020  |  Volume : 38  |  Issue : 1  |  Page : 66--71

Human papillomavirus infection rates before and after the introduction of prophylactic vaccines in Kunming, Yunnan, China

Guiqian Z1, Ziqin D1, Ya X1, Qiong W2, Xin F1, Limei B1, Hongyan Z1, Yi S1,  
1 Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
2 Shizong County People's Hospital, Qujing City, Yunnan Province, China

Correspondence Address:
Dr. Hongyan Z
The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan
China
Dr. Yi S
Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, Kunming, Yunnan
China

Abstract

Purpose: The purpose of this study was to determine the prevalence of human papillomavirus (HPV) in the population in Kunming, Yunnan, China, before and after the introduction of HPV preventive vaccines. Materials and Methods: In total, 28,959 patients were enrolled in this study between 1 January 2016 and 31 August 2019. HPVs were genotyped using a flow-through hybridisation technique, and differences in HPV infection rates before and after the introduction of an HPV vaccine were determined. Results: The prevalence of HPV before and after the introduction of HPV vaccines was 17.74% and 17.11%, respectively. This difference was not statistically significant (χ2 = 1.920, P > 0.05). The HPV infection rates showed a bimodal U-shaped curve for all age groups. The most common genotypes of HPV detected were HPV52, HPV16, HPV58 and HPV39. Conclusion: Although the overall HPV infection rate in Kunming did not change significantly after the introduction of HPV vaccines, differences in HPV infection rates and multi-typic HPV infection rates were evident in certain age groups.

How to cite this article:
Guiqian, Ziqin, Ya, Qiong, Xin, Limei, Hongyan, Yi. Human papillomavirus infection rates before and after the introduction of prophylactic vaccines in Kunming, Yunnan, China.Indian J Med Microbiol 2020;38:66-71

How to cite this URL:
Guiqian, Ziqin, Ya, Qiong, Xin, Limei, Hongyan, Yi. Human papillomavirus infection rates before and after the introduction of prophylactic vaccines in Kunming, Yunnan, China. Indian J Med Microbiol [serial online] 2020 [cited 2020 Sep 26 ];38:66-71
Available from: http://www.ijmm.org/text.asp?2020/38/1/66/290676

Full Text



 Introduction



Human papillomavirus (HPV) is the most common sexually transmitted pathogen.[1] Studies have confirmed that HPV infection is the main cause of cervical intraepithelial neoplasia and cervical cancer.[2] There are currently more than 200 subtypes, with 42 of these subtypes causing infections in the genital area. Based on carcinogenicity, HPVs are divided into high-risk and low-risk types. HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59 and HPV68 are classified as high-risk types by the International Agency for Research on Cancer.[3] High-risk HPV persistent infection is a recognised cause of various cancers and especially cervical cancer.

Cervical cancer is the third most common cancer in women worldwide.[4] More than 85% of these cases occur in developing countries, including China.[5] According to China's 2015 cancer statistics, the incidence of cervical cancer in China is the second highest in the world. Approximately 100,000 new cases of cervical cancer occur each year, with 30,000 deaths resulting annually.[6] Despite these figures, cervical cancer is the only cancer that can be prevented by vaccines. HPV transmission to uninfected people can be blocked by immunisation with an HPV prophylactic vaccine. HPV prophylactic vaccines bind the L1 protein virus-like particles to induce high-titre neutralising antibodies that block virus entry into cells and promote tumour-specific T-lymphocytes to clear the infected virus.

Three HPV vaccines have been marketed worldwide. A bivalent vaccine (Cervarix) for high-risk subtypes of HPV16 and HPV18 was launched in 2006 by GlaxoSmithKline. Merck produced a quadrivalent vaccine (Gardasil 4) against HPV6, HPV11, HPV16 and HPV18 in 2007 and a nine-valent vaccine (Gardasil 9) against HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV45, HPV52 and HPV58 in 2014. Vaccinators should be vaccinated on the 1st day and the 2nd and 6th months.[7],[8] The world's first preventive HPV vaccine has been in use for more than 10 years, and follow-up visits have shown that both the bivalent and tetravalent vaccines have good immunogenicity and are well tolerated.[9] Studies have also shown that the nine-valent HPV vaccine is safe and effective at a population scale[10],[11] and can reduce cervical cancer by 15% compared with the quadrivalent vaccine.[12] The bivalent vaccine was introduced into China in July 2016, and the four- and nine-valent vaccines were introduced in May 2017 and April 2018, respectively. In this study, we determined the prevalence of HPV in a clinical population following the introduction of these vaccines in the region.

 Materials and Methods



Subjects

A total of 28,959 patients who attended the Department of Reproductive Gynaecology in the People's Hospital of Yunnan Province from 1 January 2016 to 31 August 2019 were selected for participation in this study. Because the first HPV was introduced into Yunnan in the second half of 2017, and the establishment of continuous protection from infection requires a 6-month course of vaccination, we divided the patients into HPV vaccine pre-introduction (2016–2017) and post-introduction (2018–2019) periods. A total of 12,413 patients were enrolled in the pre-introduction group. They were divided into five groups: 351 participants ≤25 years old, 3613 participants 26–35 years old, 4279 participants 36–45 years old, 3402 participants 46–55 years old and 768 participants ≥56 years old. The mean age in this group was 41 ± 7.07 years. A total of 16,546 participants were enrolled in the post-introduction groups, with 656 participants ≤25 years old, 5896 participants 26–35 years old, 4996 participants 36–45 years old, 3680 participants 46–55 years old and 1318 participants ≥56 years old. The mean age in this group was 39 ± 9.89 years. Criteria for inclusion were the following: female, history of sexual activity, age ≥18 years, non-pregnant, no history of total hysterectomy or cervical resection, local permanent resident and agreement to receive HPV testing and participate in the study. All patients underwent pelvic examination before sample collection, and cervical cells were sampled by a trained reproductive gynaecologist. All patients provided signed informed consent, and this study was approved by the Ethics Committee of the Research Institution.

Methods

The samples obtained were extracted using 37 HPV genotyping assay kits (Chaozhou Hybribio Biotechnology, Corp.). In this experiment, DNA was extracted from lysed cells and then polymerase chain reaction (PCR) amplified. Based on complementary DNA base pairing, the PCR product was added to a low-density gene chip with various HPV subtype probes immobilised. The PCR product crossed the membrane medium by flow-through hybridisation, simultaneously generating bases through a complementary reaction with the immobilised probes. Using an alkaline phosphatase system qualitative test, specific hybridisation results were obtained. The entire experimental process involved DNA extraction, PCR amplification and hybridisation. The results were analysed within 1 h of colour development. The amplification procedure was as follows: hold: 95°C for 9 min; cycling: 95°C for 20 s, followed by 55°C for 30 s and 72°C for 30 s for 40 cycles; cooling: 72°C for 5 min; and a final hold: 4°C. The results is interpreted according to the manufacturer's instructions.

Statistical analysis

Statistical analysis of the data was performed using SPSS 22.0 software (SPSS, Chicago, USA). The count data were described in relative numbers, and groups were compared by Chi-square testing with P = 0.05 (two-tailed test) indicating significance.

 Results



Total infection analysis

The pre- and post-vaccine introduction infection rates were 17.74% and 17.11%, respectively; however, this difference was not statistically significant (χ2 = 1.920, P > 0.05). Monotypic infection rates were 12.50% and 13.47%, and this difference was statistically significant (χ2 = 5.861, P < 0.05). Multi-typic infection rates were 5.24% and 3.64%, and this difference was statistically significant (χ2 = 43.426, P < 0.05) [Table 1].{Table 1}

Comparison of infection rates in all groups

The infection rate was highest in ≤25 year olds, followed by ≥56 year olds, and the infection rate showed a double-peak U-shaped curve. The multi-typic infection rate in the post-infection in the ≤25-year-old group was less than that in the pre-introduction group. The prevalence of both the infection rate and multi-typic infection rate in the 26–35-year-old group decreases after the launching of HPV vaccine. There was no difference in monotypic infection rates. The infection rate in the 36–45-year-old group was not different before and after the use of the vaccine, and the multi-typic infection rate was higher than that before vaccine deployment. There was no statistical difference between the infection rate and single and multiple infection rates in the 46–55-year-old group. The infection rate decreased in the 56-year-old group, and there was no difference between the single and multiple infection rates [Table 2] and [Figure 1].{Table 2}{Figure 1}

Human papillomavirus genotype distribution

In this study, 36 genotypes were detected: 18 high-risk types, 11 low-risk types and 7 potentially high-risk types. The high-risk genotypes detected at the highest rates were HPV52, HPV16, HPV58 and HPV39. The low-risk genotypes detected at the highest rates were HPV81, HPV61, HPV54, HPV6 and HPV11. The highest risk of infection was for HPV84, HPV55 and HPV34. The rates of the four most common genotypes, HPV52, HPV16, HPV58 and HPV39, were not different in the before and after vaccine introduction groups [Table 1], [Table 2], [Table 3] and [Figure 2].{Table 3}{Figure 2}

 Discussion



Persistent infection with high-risk genotypes of HPV is a recognised cause of various cancers and especially cervical cancer. Asymptomatic HPV infection progression to cervical intraepithelial and then to cervical cancer is slow.[13] Cervical cancer can be prevented by the use of vaccines, and early use of a prophylactic HPV vaccine can fundamentally block HPV transmission. The three preventive HPV vaccines currently on the market have been widely used around the world. In the United States, a 4-year comparison of infection rates after the introduction of the four-valent HPV vaccine showed that the prevalence of HPV6, HPV11, HPV16 and HPV18 was reduced by 56% in girls aged 14–19 years of age.[14] Among women aged 25–29 years in Australia, the incidence of cervical precancerous lesions decreased by 17% after the introduction of this vaccine.[15] Vaccination can also indirectly protect unvaccinated populations through herd immunity. A meta-analysis from Canada confirms the effectiveness of vaccination and the group effects in unvaccinated populations.[16] This effect was also confirmed in Scotland.[17] HPV infection in men contributes to HPV infection and subsequent cervical disease in women. In order to effectively decrease the infection rate of HPV, consideration should be given to vaccinating not only females but also males.[18]

The inclusion of HPV vaccines in national immunisation programs is mainly confined to Western countries. The vast majority of Asian and African countries have not yet included these vaccines, and developing countries, including China, are facing a serious cervical cancer disease burden. Although HPV vaccines have been widely used in mainland China, their acceptance is still very low. A meta-analysis of 58 studies in 19 provinces and cities in China showed that the recognition and awareness rate of HPV vaccines in China was only 15.95% and 17.55%, respectively,[19] which are far lower than the rates in developed countries.

The infection rates before and after the introduction of the vaccine were not significant. This may be related to the fact that HPV vaccines are not yet included in the national immunisation program and the population coverage is long. The infection rates in the studies were between 12.9%[20] and 19.9%,[21] and the difference was related to the size of the population in these studies. The overall HPV infection rate in this study was much lower than the 31.5% reported in nearby provinces,[22] which is also lower than the country-wide rate of 22.3%,[23] and higher than the 8.1% in Europe and 11.3% in North America.[24] Regional differences in infection rates were confirmed in this study.

The HPV infection rate was the highest in the ≤25-year-old group, followed by the ≥56-year-old group. The HPV infection showed a bimodal U-shaped curve across ages, which was consistent with the unique pattern for Asian women.[25] The peak of infection in young women is related to the initiation of their sexual lives and inadequate sexual protection. The reason for the high rates of HPV infection among elderly women is mainly related to changes in hormone levels and low immunity. The infection rates in the before and after vaccine introduction groups were compared. The infection rates decreased from the 26–35-year-old group to the ≥56-year-old group, and this difference was statistically significant. The infection rate in the ≥56-year-old group decreased significantly after the introduction of the vaccine. The lower rates of infection rate in the younger age group may be related to higher recognition and acceptance of HPV vaccines in this age group. The lower rates in the older age group may be related to a high economic status and a high vaccination rate. The multi-infection rate in all age groups was significantly reduced. In addition to the effect of vaccination, this may be related to the integration of some viruses. A total of 36 genotypes were detected in this study, including all types of HPV included in the nine-valent vaccine. The highest infection rates before and after the introduction of an HPV vaccine were with subtypes HPV52, HPV16, HPV58 and HPV39. Rates with the first three of these were consistent with results from previous studies.[20],[21] However, the results were different from the most common subtypes HPV16, HPV18, HPV52, HPV31 and HPV58[26] reported in the world, which further confirmed the geographic differences in HPV subtype distribution. Higher infection rates in low-risk subtypes were observed for HPV81, HPV61, HPV54, HPV6 and HPV11. In this study, the infection rates of the common low-risk HPV6 and HPV11 reported in the world were relatively low, but those of HPV81 were high.

The adoption of HPV vaccines was relatively late in China. Current domestic research on HPV infection rates before and after the introduction of HPV vaccines is limited, and these numbers have not yet been reported in Yunnan Province. Due to the short duration of this study and limited population range, follow-up studies will be carried out in the future to expand the population range and learn about the changes of HPV prevalence in this region in real time, so as to provide reference data for the further promotion and application of HPV vaccine in mainland China.

 Conclusion



After the introduction of an HPV vaccine, overall HPV infection rates in Kunming did not change significantly, which may be related to the low vaccination rate, short monitoring time and insufficient group effect. However, in certain age groups, the infection rates decreased. In future studies, we need to expand the sample size and extend the monitoring time.

Acknowledgements

We would like to thank Prof. Sun for providing us with ideas for the topic of study, and we appreciate the help in sample collection and testing from Dr. Dian and Xu. In addition, we are grateful to Dr. Zhu for assistance with the statistical analysis and revision of the paper. We thank Editage (www.editage.cn) for English language editing.

Financial support and sponsorship

This work was supported by a grant from the National Natural Science Foundation of China (No. 81960606), Yunnan Applied Basic Research Program (Youth Project, No. 2019FD018) and The Association Foundation Program of Yunnan Provincial Science and Technology Department and Kunming Medical University (No. 2017FE468 (-124)).

Conflicts of interest

There are no conflicts of interest.

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