The fourth most common cancer in worldwide women is cervical cancer which is accounted for 604,127 new cases and 341,831 deaths in 2020 [1]. In South Korean women, cervical cancer is eighth most common cancer which is accounted for 3500 new cancers and 845 deaths in 2018 [2]. Human papillomavirus (HPV) is detected in 99% of all cervical cancer patients, and 70% of the cervical cancer cases are associated with HPV type 16 and 18 [3, 4, 5]. HPV vaccination can reduce the cervical cancer by preventing cervical intraepithelial neoplasia (CIN), and long-term clinical efficacy studies in naive populations have shown 90–100% efficacy of the HPV vaccine against CIN2 or CIN3 [6].

The quadrivalent HPV vaccine was approved by the United States Food and Drug Administration in 2006, the bivalent HPV vaccine was licensed in 2009, and the 9-valent HPV vaccine was licensed in 2014. The Advisory Committee on Immunization Practices recommends routine vaccination for girls aged 11–12 years, and “catch-up” vaccination for women aged 13–26 years with these HPV vaccines [7]. In Korea, The Korea Society of Gynecology Oncology has recommended a quadrivalent and bivalent vaccine to 9–26 years old women. In middle-aged women, the followings were recommended. HPV preventive vaccine has a preventive effect in middle-aged women (27 to 45 years); before vaccination, a clinical assessment of individual patient risk and state of inoculation should be performed [8]. HPV vaccination was provided through both public and private sector in South Korea. The cost of vaccine was about 150,000–200,000 KRW (about 150 US Dollar) for the 1 dose of vaccination.

Nowadays, the HPV vaccine is covered by national vaccination programs in many developed countries. In some countries, such HPV vaccination programs are offered through schools (e.g., Australia, UK, Portugal), and the coverage rate (3 doses) of HPV vaccination in these countries is 64–81% [9]. HPV vaccination was scheduled to be covered by the National Immunization Program (NIP) in South Korea from the June, 2016. Reliable data on the HPV vaccination rate before NIP remains unavailable. An analysis of the HPV vaccine uptake status and associated factors will be important to implement the National HPV vaccination program successfully.

This study aimed to assess the HPV vaccine uptake rate in South Korean women and to identify factors that affected the vaccine uptake before the NIP began through a sample survey.

To our knowledge, our study is the first report about HPV vaccine uptake in South Korea before the NIP began. Our results showed that the HPV vaccine uptake at least one dose among South Korean women was low (23.1%), especially among women aged 9–19 years (16.9%), compared to the coverage rates reported in countries that have implemented a national HPV vaccination program. In the United States, among the 13–17-year-old women, the HPV vaccination coverage rate (at least 1 dose) was 60.0% and the rate of complete vaccination was 69.3% [11]. In Australia, among girls who turned 15 in the year 2015, the coverage rate of single dose HPV vaccination was 85.6%, while the coverage rate of 3-dose vaccination was 77.4% [12]. Netherlands, Italy, and Denmark offer HPV vaccination through health care providers, and the coverage rate of the 3-dose HPV vaccination in teenage girls from these countries is 45–58% [9, 13]. The vaccine delivery strategies employed by the national vaccination programs play a major role in determining the vaccination coverage. HPV vaccination was scheduled to be covered by the NIP for 12 years old girls in South Korea from the June, 2016. HPV vaccination rate of 12 years old girls in South Korea is 83.5% in October, 2019 [14].

HPV vaccine is most effective when administered to adolescent girls before their first sexual contact [7, 15]. As vaccination at this age results in higher antibody titers than vaccination at an older age [16], most national HPV vaccination programs target adolescent girls in their early teens. Further, because the non-inferior antibody levels after HPV vaccination were shown in women 27–45 years compared with women 16–26 years of age, HPV vaccine is also important in adult women [17].

In our study, vaccination rate was significantly lower in aged 9–19 years compared with subjects aged 20–39 years. Among unvaccinated 9–19-year-old girls, “concerned about vaccine safety” was the most common reason for remaining unvaccinated (27.1%, data not shown). This result indicates that the availability of accurate information on HPV vaccine safety is important in increasing vaccine uptake. A previous study also suggests that the vaccine uptake in adolescent females may reflect the knowledge and attitude of parents or healthcare providers regarding the HPV vaccine [18]. According to a recent updated review, the risk-benefit profile for HPV vaccines remains highly favorable. There was no consistent evidence of an increased risk of any adverse event of special interest, including demyelinating syndromes or neurological conditions such as complex regional pain or postural orthostatic tachycardia syndrome [19].

Previous studies from the United States have reported that rural regions are at a disadvantage as they have fewer health care providers and women have to travel longer distances to access health care [20, 21, 22]. In our study, the HPV vaccine uptake rate was higher in the six metropolitan cities than in other regions (p = 0.003). Fewer health care providers, public relations, and HPV vaccine related awareness may be the reasons for the low HPV vaccine uptake in the rural regions of the South Korea.

It was reported that vaccine uptake was affected by various factors including race, age, knowledge of HPV vaccination among adolescents and their parents, and health care utilization [9]. In our study, higher educational status and family income were both significantly associated with HPV vaccine uptake. In South Korea, universal health insurance is provided to all people regardless of income level or health risk. However, HPV vaccine is not applicable before the NIP began. So, economic issue may play a role on vaccine uptake rate. In our survey, the cost of the vaccine was one of the main reasons for withholding vaccine uptake in the unvaccinated women (24.1%). The NIP of South Korea offer complimentary HPV vaccination by bivalent or quadrivalent vaccine to 11 and 12-year-old girls through health care providers. The complimentary vaccination could solve the effect of economic disparity on vaccine uptake. Preventive health behaviors such as “clinic visit within the last 6 months”, “regular influenza vaccination” were associated with the HPV vaccine coverage rate in our results. These results are consistent with several previous studies [23, 24, 25]. Family history of cervical cancer was not associated with uptake of the HPV vaccine in our result. In previous report, family history of cervical cancer was associated with positive attitudes for HPV vaccine [26]. We think that this did not lead to actual vaccination in our study. It would have been affected by the high cost of HPV vaccine, the fear of side effects and lack of knowledge about HPV vaccine as shown in Table 3.

Our study has several limitations. The survey agency accumulated the panels over a period of more than 10 years through a systematic probabilistic sampling to achieve sample representativeness. However, owing to the self-reported online nature of the survey, the representativeness of the survey panels and the reliability of replies may be limiting. As our study population included a wide age range, some of the age-based subgroups comprised a very small number of samples, and this may have decreased the statistical reliability of some of our results.

Based on our results, the HPV vaccine uptake rate in South Korean women is low, especially in adolescent girls or women living in the rural regions. Our study identified various demographic, socioeconomic, preventive health behavioral factors, cost to vaccination and concerning about vaccine side effect were affected the HPV vaccine uptake rate in South Korean women. The national HPV vaccination program will improve the vaccine uptake rate by overcoming barriers to costs. Therefore, it seems necessary to promote and educate parents, health care providers, as well as women, about effect of HPV vaccination, NIP, correct information about side effect of HPV vaccine. This could solve the problem of situation that people are hesitant to vaccinate due to the concerns about side effects and difference of vaccine uptake by region. This study is the first to report data on HPV vaccination rate by distribution of age and region in South Korean women before the NIP began. And our data could help to lay essential groundwork for future research on HPV vaccination in South Korea.

CJY, KMS, KBS, JSJ, SDH, and NJH conceived and designed the study. CJY, SDH, NJH, KKD, and KYB collected the data, and all authors analyzed and interpreted the data. CJY, JSJ, SDH, and NJH reviewed all statistical analysis. CJY and NJH wrote the manuscript; all authors approved the final version of the submitted manuscript.

This retrospective study was granted ethical approval by the Institutional Review Board approval (IRB number: X-1601/332-902l), and the study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. We did not include personally identifiable information in the survey, and our research involved no more than minimal risk to the subject. The institutional review board waived the need for consent forms for this study.

Thanks to all the peer reviewers for their opinions and suggestions.

This research was funded by the Seoul National University Bundang Hospital [grant numbers 14-2015-026].

The authors declare no conflict of interest.