Predicted Cervical Cancer Prevention: Impact of National HPV Vaccination Program on Young Women in South Korea

Kyeongmin Kwak; Seung-sik Hwang

doi:10.4143/crt.2023.981

Articles

Page Path: HOME > Cancer Res Treat > Volume 56(3); 2024 > Article

Original Article Gynecologic cancer Predicted Cervical Cancer Prevention: Impact of National HPV Vaccination Program on Young Women in South Korea: Kyeongmin Kwak^1,2, Seung-sik Hwang^3,; Cancer Research and Treatment : Official Journal of Korean Cancer Association 2024;56(3):898-908.
DOI: https://doi.org/10.4143/crt.2023.981
Published online: January 15, 2024

¹Department of Occupational and Environmental Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea

²Department of Environmental and Occupational Health, Korea University Graduate School of Public Health, Seoul, Korea

³Department of Public Health Sciences, Seoul National University Graduate School of Public Health, Seoul, Korea

Correspondence: Seung-sik Hwang, Department of Public Health Sciences, Seoul National University Graduate School of Public Health, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
Tel: 82-2-880-2715 Fax: 82-2-762-2888 E-mail: cyberdoc@snu.ac.kr

• Received: August 29, 2023 • Accepted: January 11, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

5,937 Views
169 Download

prev next

Full Article

Download PDF

Abstract

Purpose
This study aimed to evaluate the effectiveness of the national human papillomavirus (HPV) vaccination program of South Korea among its entire female population, particularly among younger age groups.
Materials and Methods
We first predicted the incidence of cervical cancer over the next 20 years (2021-2040) using the Nordpred package based on Møller’s age-period-cohort model under several scenarios for the national HPV vaccination program. We calculated the potential impact fractions and proportional differences under the current national vaccination programs, and alternative scenarios using the no-vaccination assumption as a reference.
Results
We estimated that the current national vaccination program would prevent 4.13% of cervical cancer cases and reduce the age-standardized incidence rate (ASR) by 8.79% in the overall population by 2036-2040. Under the alternative scenario of implementing the nine-valent vaccine, 5.13% of cervical cancer cases could be prevented and the ASR reduced by 10.93% during the same period. In another scenario, expanding the vaccination age to 9-17 years could prevent 10.19% of cervical cancer cases, with the ASR reduced by 18.57% during the same period. When restricted to ages < 40 years, the prevention effect was remarkably greater. We predict that the current national HPV program will reduce its incidence by more than 30% between 2036 and 2040 in women aged < 40 years.
Conclusion
The effectiveness of the vaccination program in reducing the incidence of cervical cancer was confirmed, with a considerable impact anticipated in younger age groups.
Key words: Uterine cervical neoplasms, Papillomavirus vaccines, Human papillomavirus viruses, Potential impact fraction

Introduction

Cervical cancer develops in the cervix, which is the lower part of the uterus that connects to the vagina [1]. Cervical cancer is the fourth most common malignancy in women worldwide, with an estimated 604,000 new cases and 342,000 deaths reported in 2020 [2]. In South Korea, cervical cancer is the tenth most common cancer in women, with 2,998 new cases and 810 deaths in 2020 [3,4]. Almost all cervical cancer cases are caused by the human papillomavirus (HPV), which is sexually transmitted [5-7]. After HPV infection, cervical cancer develops over a latent period of 10-20 years [8]. All forms of cervical cancer can be caused by 15 different HPV strains [9], of which HPV 16 and 18 are responsible for approximately 70% of cervical cancer [10]. Thus, vaccination against HPV types 16 and 18 substantially reduces the risk of developing cervical cancer, and HPV vaccination is the most cost-effective public health intervention for the prevention of cervical cancer [11].

Currently, three HPV vaccine types are authorized for use. Cervarix, a bivalent vaccine against HPV types 16 and 18, has been in use since 2008. Additionally, Gardasil, a quadrivalent vaccine against HPV types 6, 11, 16, and 18, has been administered since 2007. The nine-valent vaccine known as Gardasil 9, introduced in 2016, is also effective against HPV types 31, 33, 45, 52, and 58, extending the coverage of the original quadrivalent Gardasil vaccines. All three vaccines showed 92%-100% prophylactic effects against HPV 16 and 18 [12]. All three vaccines have a relatively similar effectiveness in preventing cervical cancer [13]. The World Health Organization (WHO) does not endorse the preference for any specific HPV vaccine. However, the HPV nine-valent vaccine has greater HPV-type coverage, and only nine-valent vaccines have been available in the United States since 2017 [14]. The Centers for Disease Control and Prevention (CDC) in the United States recommend HPV vaccination for individuals aged 9-26 years, with a two-dose schedule administered 6-12 months apart for those up to 14 years of age, and a three-dose schedule administered within 6 months for those aged 15-26 [15]. The WHO recommends a two-dose schedule for girls aged 9-14 years and a three-dose schedule for those above the age of 15, similar to the recommendation of the U.S. CDC [16]. In April 2022, the vaccination recommendations were revised based on recent studies showing that a single dose of HPV vaccination can provide an efficacy similar to that of a two-dose schedule [17-19]. The WHO Strategic Advisory Group of Experts (SAGE) now recommends a one- or two-dose schedule for girls up to 20 years of age, including the primary target group of 9-14 year-olds, and a two-dose schedule with a 6-month interval for those aged 21 years or older [20].

In South Korea, HPV vaccination has been implemented as a national vaccination program since June 2016. Annually, two doses of bivalent and quadrivalent vaccines at intervals of six months are administered to 12-year-old girls. In the first year of the program, 61.8% and 54.9% of the subjects completed the first and second vaccinations, respectively. While the vaccination rate barely reached the halfway mark, it exhibited an increase each subsequent year until 2021, when nearly 90% of females had received their first vaccination, and about two-thirds had completed the full vaccination regimen. Starting in 2022, the vaccination efforts were expanded, with the target age range for vaccination extended to include individuals between the ages of 12-17 years. Adolescent females up to the age of 17 years who were not vaccinated before the age of 12 years prior to 2021 were eligible to receive the vaccine. Considering the vaccination age and operation period of the national vaccination program, it is difficult to anticipate a short-term cancer prevention effect in the entire population, although it may be of great help in the distant future. Thus, to gauge the short-term future effect of the national vaccination program, it is necessary to assess the prevention of cervical cancer among individuals in their 20s and 30s.

Therefore, this study aimed to evaluate the effectiveness of the national HPV vaccination program in South Korea by projecting the potential reduction in cervical cancer cases in the entire female population, especially in younger women, over the next 20 years through this vaccination program. Additionally, this study aimed to predict and compare the effects of vaccination programs against cervical cancer using an alternative scenario based on the vaccine type.

Materials and Methods

1. Data on cervical cancer incidence

We used data on the incidence of cervical cancer (C53) from the Korea Central Cancer Registry (KCCR) from 2001 to 2020, which was available on the homepage of the KOSIS (http://kosis.kr) without restrictions. Data from the KCCR are highly accurate for cancer diagnosis and considered reliable for determining the actual incidence [21,22]. For the prediction model, the incidence of cervical cancer was organized according to sex over 5-year epochs (2001-2005, 2006-2010, 2011-2015, and 2016-2020).

2. Data on population

Population data are needed to determine the incidence rate and predict future cancer incidence. Annual resident registration data (2001-2022) and prospective resident data (2023-2040) were obtained from the KOSIS. To apply to the prediction model, population data were organized in 5-year epochs (2001-2005, 2006-2010, 2011-2015, 2016-2020, 2021-2025, 2026-2030, 2031-2035, and 2036-2040). Cervical cancer incidence and resident data were further divided into age groups using 5-year units (0-4, 5-9, 10-14, 15-19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80-84, 85+ years of age).

3. Data on HPV vaccination

We obtained the HPV vaccination rate statistics from the Korea Disease Control and Prevention Agency (KDCA) in early 2023. We obtained the vaccination rates in the project year and cumulative vaccination rates by year of birth (2003-2009) from the KDCA and present them in S1 and S2 Tables, respectively. Until 2021, the vaccination project was conducted only for 12-year-old girls, and the vaccination rate in the project year represented the final vaccination rate in the year of birth. However, as of 2022, the target age for vaccination has expanded to 12-17 year-olds. This adjustment permits the administration of supplementary vaccinations to those born between 2004 and 2008 who had not completed the HPV vaccination doses previously. As a result, there may be a difference between the vaccination rates in the project year and the cumulative vaccination rates. Since those born in 2003 were not eligible for the expansion of the target age for vaccination in 2022, the vaccination rate in the project year was used as the final vaccination rate statistics. Conversely, for those born in 2004, the cumulative vaccination rate statistics as of 2022 were used as the final vaccination rate. Additional vaccinations were anticipated for those born between 2005 and 2008, extending until the age of 17 years; this projection was based on the disparity between the vaccination rate in the project year and the cumulative vaccination rate as of 2022. In addition, the increase in vaccination was found to converge at 95% for the first vaccination and 85% for the second vaccination. For those born in 2009 and later, the first and second vaccination rates were set at 95% and 85%, respectively, and were used to predict the future incidence of cervical cancer. The estimated vaccination rate by birth year used to predict future cervical cancer is presented in S3 Table.

4. Assumption

The following assumptions were made to determine the cancer prevention effect of the HPV vaccine: (1) All cervical cancers are caused by HPV infection [23]. (2) Based on the proportion of HPV types in Korea [24], 74% of HPV infections are attributed to HPV 16 and 18, and this increases to 92.0% when including HPVs 31/33/45/52/58. (3) The effectiveness of HPV vaccines is 92% [25]. (4) The age at which HPV infection begins is 19 years because the highest prevalence of HPV is observed in the late teens and early 20s [26]. (5) The latent period from HPV infection to the onset of cervical cancer was not considered. (6) Based on the updated recommendation of the WHO, a single dose of HPV vaccination is effective in preventing cervical cancer. (7) HPV vaccination prior to the national HPV vaccination program, cervical cancer screening, and individual sexual behaviors were not considered.

5. Vaccination scenarios

The following vaccination scenarios were considered: Scenario 1, Without a national vaccination program; Scenario 2, Current HPV national vaccination program; Scenario 3, Use of a 9-valent vaccine; and Scenario 4, Expansion of vaccination age (Table 1).

6. Prediction model

Møller’s age-period-cohort (APC) method is widely used to predict cancer occurrence. The Nordpred package, which is an R package function used for predicting trends in cancer incidence developed by the Norwegian Cancer Registry based on the Møller’s APC model, was used for the statistical analysis. WHO’s GLOBOCAN project recommends using the Nordpred package for cancer incidence prediction when national incidence data are available [27]. Thus, we used the Nordpred package to predict the future incidence rate of cervical cancer.

7. Statistical analysis

Using the Nordpred package, we projected the number of incident cases and calculated the crude and age-standardized incidences of cervical cancer from 2021 to 2040 under the scenarios of the national vaccination program. To calculate the age-standardized incidence rate, we used the WHO world population for the years 2000-2025 as the standard population [28]. We calculated the incidence rate of cervical cancer from 2001 to 2020 and presented it along with the projected incidence rate. We calculated the potential impact fraction (PIF) as follows:

PIF=I0-IiI0

where, I₀: incidence rate under the no-vaccination assumption; I_i: incidence rate under the current national vaccination program or alternative scenario.

Due to the risk of not implementing a national vaccination program, the PIF is in line with the attributable fraction (AF) when comparing the assumption of no-vaccination program with the current vaccination program or an alternative scenario. By employing the formula to calculate the confidence interval (CI) of AF [29], we obtained the 95% CIs for PIF as follows:

PIF-z0.975VAR(IiI0), min PIF+z0.975VAR(IiI0), 1 withVAR(IiI0)=(IiI0)2·1-IiN·Ii+1-I0N·I0,

where N is the number of population.

In particular, when considering the vaccination age, the crude and age-standardized incidence rates, PIFs, and their 95% CIs for the 20s-30s age groups were calculated.

Results

We predicted the development of cervical cancer over the next 20 years (2021-2040), with and without the national HPV vaccination program. Moreover, we predicted the development of cervical cancer under alternative scenarios of the vaccination program over the same period. The incidence rate of cervical cancer per 100,000 persons has continued to decrease from a crude incidence rate (CR) of 18.047 and an age-standardized incidence rate (ASR) of 15.508 in 2001-2005 to a CR of 13.234 and an ASR of 9.397 in 2016-2020. Additionally, the incidence rate over the next 20 years showed a decreasing trend. The CR was predicted to continue to decrease to 10.693 in 2036-2040, while the ASR was predicted to continue to decrease to 7.923 in 2031-2035 and subsequently slightly increase to 8.011 in 2036-2040 (Fig. 1, S4 Table).

The effect of the national HPV vaccination program did not differ from that of not introducing the program until 2021-2025. However, from 2026-2030, the effect of the vaccination program was predicted to gradually appear, and the effect would be slightly greater from 2036-2040. The current national HPV vaccination program is estimated to prevent 818 cases of cervical cancer over the next 20 years. The incidence of cervical cancer is projected to be reduced by 4.13% (PIF, 4.13%; 95% CI, 1.82% to 6.43%) for CR and 8.79% (PIF, 8.79%; 95% CI, 6.23% to 11.36%) for ASR in 2036-2040. When the nine-valent vaccine was used instead of the current 2- and quadrivalent vaccines, the number of preventable cervical cancers over the next 20 years was predicted to reach 1,016 cases. It was predicted to reduce the incidence of cervical cancer by 5.13% (PIF, 5.13%; 95% CI, 2.84% to 7.42%) for CR and 10.93% (PIF, 10.93%; 95% CI, 8.41% to 13.46%) for ASR in 2036-2040. This is more effective than the current national vaccination program by 1% for CR and 2% for ASR. In the scenario that expanded the target population from the initiation of the vaccination program to individuals aged 9 to 17 years old, including 9 to 14 years old, which is the first target in the WHO recommendation, the projected number of preventable cervical cancers over the next 20 years substantially increased to 2,486. Moreover, it was predicted to reduce the incidence of cervical cancer by 10.93% (PIF, 10.93%; 95% CI, 8.41% to 13.46%) for CR and 18.57% (PIF, 18.57%; 95% CI, 16.21% to 20.93%) for ASR in 2036-2040. This indicates an effect that is more than twice as large as that of the current national vaccination program (Table 2, Fig. 2).

When limited to their 20s and 30s, the preventive effect was predicted to be greater. It was predicted to prevent 560 cases of cervical cancer in 2036-2040, which is approximately 30% of cervical cancer cases in the 20s and 30s (PIF, 30.12%; 95% CI, 25.16% to 35.07% for CR). When age-standardized, it was predicted that approximately 34% of cervical cancer cases in the 20-30 age group could be prevented in 2036-2040 (PIF, 33.51%; 95% CI, 28.42% to 38.61% for ASR). In addition, in the alternative nine-valent vaccination scenario, the preventive effect was predicted to be slightly greater than that of the current vaccination program, and approximately 40% of cervical cancer cases in the 20-30 age group is predicted to be prevented in 2036-2040 (PIF, 37.45; 95% CI, 32.86% to 42.03% for CR and 41.67; 95% CI, 37.01% to 46.32% for ASR). Regarding the alternative vaccination scenario for expanding the target age, the preventive effect was predicted to be even greater, and over 60% of cervical cancer cases in the 20-30 age group were predicted to be prevented in 2036-2040 (PIF, 61.17; 95% CI, 57.83% to 64.51% for CR and 61.56; 95% CI, 58.03% to 65.10% for ASR) (Table 3, Fig. 3).

When examining the 20s age group, the preventive effect was predicted to be much greater in each vaccination scenario. The detailed values for each scenario are listed in the S5 Table.

Discussion

We predicted the incidence of cervical cancer over the next 20 years, and calculated the potential impact of the Korean National HPV Vaccine Program. It was estimated to prevent approximately 4.13% of cervical cancer cases in the total population in 2036-2040. Additionally, when age-standardized, it was predicted to prevent 8.79% of cervical cancer cases in the entire population over the same period. We calculated the potential impact of the alternative vaccination scenarios on the national vaccination program. The scenario using a nine-valent vaccine was predicted to prevent 5.13% of cervical cancer cases in the total population and 10.93% of cervical cancer cases when age-standardized in 2036-2040. In another scenario, by expanding the vaccination age to 9-17 years, the preventive effect was predicted to reduce 10.19% of cervical cancer cases in the total population and 18.57% of cervical cancer cases when age-standardized during the same period.

When the age range was limited to the 20-30 age group, the current national HPV vaccination program was predicted to exhibit an earlier and greater predictive effect than in the entire population. It is estimated to prevent approximately 30% of cervical cancer cases, and about one-third in 2036-2040 when age-standardized. In the nine-valent vaccination scenario, cervical cancer was predicted to be reduced by 37.4% regardless of age, and by 41.7% when age-standardized in 2036-2040. In the scenario where the vaccination age is expanded, cervical cancer was predicted to decrease by approximately 60%, both with and without age-standardization. This suggests that the preventive effect of the cervical cancer vaccine becomes apparent in young women in their 20s and 30s, which corresponds to 10 years or more after vaccination.

This study is the first to estimate the number of cervical cancers that can be prevented in the future through Korea’s national HPV vaccination program by calculating PIFs. Kim et al. [24] suggested the potential impact of HPV vaccines; however, they only presented data on the distribution of HPV types among cervical cancer cases in South Korea and failed to consider the effect of the national HPV vaccination program. It is difficult to confirm the direct success of vaccination programs in preventing cervical cancer. The targeted vaccination group comprises girls, and a certain span of time is required before the HPV infection manifest as cancer. Moreover, the national HPV vaccination program has been implemented only recently. To overcome these limitations, we predicted the effect of disease prevention by making several assumptions using a cancer prediction model. When using a cancer prediction model, if the attributable fraction of the risk factors that cause cancer is well known, the cancer prevention effect can be predicted according to the scenario in which the risk factors are removed. Although their study was not on cervical cancer, Olsen et al. [30] predicted the number of melanoma cases that could be prevented by each intervention scenario if the number of people who regularly applied sunscreen increased. Similarly, we attempted to predict the cancer-prevention effects of the national HPV vaccination program based on the concept proposed by Olsen et al. [30]. We made some assumptions based on general facts and the results of previous studies on HPV and cervical cancer. Based on these assumptions, we predicted the cancer incidence effect for the next 20 years by specifically estimating the number of preventable cancer cases, considering the cohort effect of the age group at which vaccination was administered.

As of October 2020, 110 countries worldwide have implemented national HPV vaccination program [31,32]. At the population level, there is evidence of a reduction in high-grade cervical abnormalities among young women [33-35] and vaccination significantly reduces the prevalence of high-risk HPV types among young women [36]. Several studies have investigated the cost-effectiveness of HPV vaccines against cervical cancer in various countries [37]. Despite different methodologies and assumptions, most studies have consistently shown that HPV vaccination has an economic effect, and many countries have introduced it as a national vaccination program. The WHO also targets 90% HPV vaccination of girls under the age of 15 years by 2030, along with cancer screening and treatment, as targets for cervical cancer elimination [38].

Our predictive analysis showed that the nine-valent vaccine introduction scenario had a slightly higher cervical cancer prevention effect than the current national vaccination program. Specifically, in young women in their 20s-30s, it is predicted to prevent cervical cancer by approximately 7%-8% compared to the current vaccination program in 2036-2040. The nine-valent vaccine covers 5 additional HPV types (31, 33, 45, 52, and 58) that cause cervical cancer. This provides 15%-20% additional coverage than bivalent or quadrivalent vaccines, thereby preventing 90% of the HPV types related to cervical cancer [39]. Therefore, these vaccines are expected to prevent cervical cancer. In developed countries, such as the United States [14] and Australia [40], bivalent or quadrivalent vaccines have been replaced by a nine-valent vaccine in their national vaccination program. In addition, several clinical trials have shown that it is as safe as bivalent or quadrivalent vaccines [41]. While we cannot definitely assert that the nine-valent vaccines are more cost-effective than those being used in the current national vaccination program, their inclusion is also worth considering if there are no cost-related barriers.

In the predictions for each scenario, the scenario in which the age was expanded from the beginning of the project to 9-17 years old, including the WHO-recommended age (9-14 years old), was observed to have a much greater preventive effect over the next 20 years than the current scenario. The current national vaccination program has expanded the vaccination age to 12-17 years old, starting in 2022, where it was previously conducted for 12-year-olds. Expanding the target age broadens the impact of the vaccination program by increasing the proportion of vaccinated people, particularly among younger age groups, thereby advancing the effectiveness of the vaccination initiative over an extended period and enhancing its short-term effects. In particular, if the age group of 9-11 years is included in the vaccination target population, along with the WHO recommendations, vaccination coverage in the population can be further increased. The vaccine uptake was highest in this age group before the age of 13 years, and beyond that, the uptake gradually decreased with age [42,43]. Additionally, the HPV vaccine is most effective before HPV infection because there is little sexual activity before the age of 12 [44]. Thus, expanding the vaccination age to include younger individuals can increase vaccination coverage and further enhance the preventive effect, making it worthy of consideration in future policy deliberations.

Based on recent studies indicating that the efficacy of a single vaccination dose is comparable to that of a full dose, we conducted a predictive analysis based on first-dose vaccination statistics rather than second-dose vaccination statistics. Kreimer et al. [17] examined HPV 16/18 infections and antibody responses in a cohort of 1,783 individuals aged 18-25 in Costa Rica who received at least one dose of the HPV16/18 vaccine, along with a control group matched 1:1 by sex and region, over an 11-year period. The study found that single-dose vaccine efficacy (VE) against HPV16/18 infection remained high, and the levels of HPV16/18 antibodies remained stable. In another study, Basu et al. [18] enrolled 17,729 girls aged 10-18 from multiple centers in India who received one or more doses of the vaccine and followed them for 10 years. The study showed that a single dose of the HPV vaccine provides similar protection against persistent infection from HPV 16 and 18 as two or three doses. Furthermore, Barnabas et al. [19] recruited 2,275 Kenyan females aged 15-20 years and randomly assigned them to three groups: one receiving a nine-valent HPV vaccine, another receiving a bivalent HPV vaccine, and a third receiving a meningococcal vaccine. Eighteen months after vaccination, the levels of HPV 16/18 antibodies were measured. The results indicated that a single dose of either bivalent or nine-valent HPV vaccine demonstrated a 97.5% preventive effect, highlighting the efficacy of a single dose for cervical cancer prevention. However, a study by Toh et al. [45] in 2015 involving 200 Fijian girls aged 15-20 years, who were assessed for HPV antibody response 6 years after receiving the HPV4 vaccine showed that the HPV antibody levels in girls who received only one dose were significantly higher than those in unvaccinated individuals, but statistically lower than those who received two or three doses. Although the equivalence of one dose to two remains controversial, almost all studies have shown that a single dose provides a much higher long-term cervical cancer prevention effect than no-vaccination. In addition, even if a statistically significant difference exists between single-dose and two-dose vaccinations, the magnitude remains relatively small. Thus, omitting the attenuation due to only one vaccination would have a minimal impact on overestimating the prevention effect. Hence, we deemed it preferable to prioritize the prediction of the cervical cancer prevention effect by utilizing the first-dose vaccination rate.

The latency period was not considered in this analysis. The latency period between initial HPV exposure and the development of cervical cancer varies; but is known to be 15-20 years on average, according to the WHO [13]. Although overestimation of the prevention effect may occur because the latency period was not considered, our analysis is expected to predict cervical cancer in the age group under the age of 40 years, given the age at vaccination, the time at which the national vaccination program starts, and the projection period in the future. In South Korea, as of 2020, the number of cases of cervical cancer was the highest in the age group of 50-54 years. The age-specific incidence showed an intermediate peak at 8.8 per 100,000 population in the age group of 50-54 years and subsequently decreased, only to increase again in the age group of 75-79 years, reaching 9.4 per 100,000 population, and peaking in the age group of 85 years and above at 12.6 per 100,000 population. Cervical cancer is rare in young individuals, particularly those in their 20s. This could be attributed to the short interval between exposure to HPV after sexual activity and cancer development, suggesting a shorter latency period than the commonly known latency period. Had we incorporated the latency period in our analysis, explaining the occurrence of cancer among individuals in their 20s after the initiation of the national vaccination program would have posed challenges. Therefore, we did not consider the latency period as a critical factor in predicting the prevention effect among individuals aged 20-30 over the next 20 years.

We assumed that the age at which HPV infection begins is 19 years because the HPV infection rate is highest in the late teens and early twenties. According to domestic surveys, women aged 18 to 29 had the highest HPV infection rate at 49.9% [46]. While HPV infection can occur at earlier ages, the occurrence of cervical cancer in this age group is shallow. Therefore, we believe that it would not have had a significant impact on our predictions.

We did not consider individual vaccinations prior to the national HPV vaccination program. Before the national vaccination program, no precise statistics were available regarding pre-vaccination coverage rates. However, based on a 2013 survey conducted by the Korea Centers for Disease Control and Prevention, which reported a vaccination coverage rate of 12.6% among individuals aged 19 years and older, it can be estimated to be approximately 10%-15% [47]. Our predictions did not account for this, which may have led to an overestimation of the projected number of cervical cancer cases. Nevertheless, considering that the national vaccination program primarily targets young girls and personal vaccinations within that age group are likely to be limited, we believe that this would have a minimal impact on the future incidence of cervical cancer among younger age groups.

In addition, factors such as HPV screening and individual sexual behavior related to the incidence and prevention of cervical cancer in the future were not considered. Additionally, it was impossible to obtain or include these data in the analytical model. Failure to consider factors related to cervical cancer development may lead to a bias in the predicted number of incident cases of cervical cancer. We assume that the HPV vaccination program did not affect the need for cancer screening. HPV screening plays an important role in preventing cervical cancer and is recommended by the WHO [48]. However, HPV screening is an ongoing program; and screening rates have remained relatively consistent. Therefore, it is unlikely that this had a significant impact on our estimation of the effects of the national HPV vaccination program on cervical cancer prevention. Similarly, while there is a lack of data on individual sexual behavior, it is challenging to ascertain whether there have been significant societal changes in the sexual behavior of young women before and after the introduction of the HPV vaccination program. Therefore, we believe that such factors are unlikely to have influenced our predictions.

The main limitation of this study is that the preventive effects were estimated using assumptions for HPV and cervical cancer. Assumptions regarding the contribution of HPV risk, VE, and the prevalence of HPV 16 and 18 in the Korean population are based on known data and are not expected to be variable. However, the other assumptions may affect the results. However, a sensitivity analysis cannot be performed individually for all these assumptions. Another limitation is the omission of vaccination rates in non-eligible populations. According to a 2013 survey that revealed a vaccination rate of 15.9% among women aged 27-39 years [47], it is evident that a significant number of women aged above the eligible population age range are opting for HPV vaccinations. Our study did not account for this, which could lead to overestimating the effectiveness of the national HPV vaccination program. Lastly, the prediction model projected the incidence of cervical cancer only for the next 20 years. Considering that the national vaccination program has only recently been introduced, the prediction was limited to fully understanding the effects of the vaccine. However, if more data are accumulated over time, we believe that future predictive studies will compensate for these limitations and be fully aware of the effects of the vaccine.

Despite these limitations, this study is the first to quantitatively predict and evaluate the cancer prevention effects of an HPV vaccination program. While existing cost-effectiveness studies have not considered the incidence of cervical cancer, our study used existing cervical cancer incidence data and prediction models to calculate future preventable cancer cases, thereby enhancing the reliability of the analysis and enabling the approach from a more public health perspective. Despite the relatively short duration since the national vaccination program was implemented, its effectiveness has been validated in young women. This study confirmed the effectiveness of the national HPV vaccination program and provided important evidence for the future expansion of the national vaccination project in South Korea.

In this prediction, the current national HPV vaccination program is estimated to prevent approximately 4.1% of the crude incidence and 8.8% of the age-standardized incidence of cervical cancer in the overall population in 2036-2040. Assuming that the nine-valent vaccine was implemented in the national vaccination program, the vaccination effect appeared to be slightly greater. In addition, when the target age for vaccination was expanded, the effect appeared to increase considerably as population coverage increased. Although the potential impact within the next 20 years is not great in the general population, the effect was found to be significant even within the next 20 years in younger age groups, especially those in their 20s-30s, when considering the age at vaccination and time to HPV infection. Although the incidence of cervical cancer has been decreasing even before the implementation of the national vaccination program, it is conceivable that the program will help accelerate this trend. If national vaccination continues for a significant period, it is thought to contribute to a substantial reduction in cervical cancer, not only among young individuals, but also across all age groups, and may potentially eliminate cervical cancer.

Electronic Supplementary Material

Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).

crt-2023-981-Supplementary-Table-S1.pdf

crt-2023-981-Supplementary-Table-S2.pdf

crt-2023-981-Supplementary-Table-S3.pdf

crt-2023-981-Supplementary-Table-S4.pdf

crt-2023-981-Supplementary-Table-S5.pdf

NOTES

Author Contributions

Conceived and designed the analysis: Kwak K, Hwang SS.

Collected the data: Kwak K.

Contributed data or analysis tools: Kwak K.

Performed the analysis: Kwak K, Hwang SS.

Wrote the paper: Kwak K, Hwang SS.

Revised the draft: Kwak K, Hwang SS.

Conflicts of Interest

Conflict of interest relevant to this article was not reported.

Acknowledgements

This study was supported by a grant from Korea University in 2023.

Fig. 1.

Trends of observed and predicted cervical cancer incidence under the scenarios for HPV national vaccination program. ASR, age-standardized incidence rate; CR, crude rate; HPV, human papillomavirus.

Fig. 2.

Trends of potential impact fractions with 95% confidence intervals by HPV vaccination scenarios in South Korea (2021-2040). 2: scenario for current national vaccination program; 3: scenario for use of nine-valent vaccine; 4: scenario for expansion of vaccination age. HPV, human papillomavirus.

Fig. 3.

Trends of potential impact fractions with 95% confidence intervals by HPV vaccination scenarios in 20s-30s in South Korea (2021-2040). 2: scenario for current national vaccination program; 3: scenario for use of nine-valent vaccine; 4: scenario for expansion of vaccination age. HPV, human papillomavirus.

Table 1.

Summary and descriptions of vaccination scenarios

Scenario name	Description
Scenario 1	Assuming that the HPV national vaccination program has not been implemented.
Scenario 2	Current HPV national vaccination program and vaccination rate.^a)
Scenario 2	Applying the increasing trend of vaccination rates for girls born in 2005 and after.
Scenario 3	Only 9-valent vaccine was used instead of the current bivalent or tetravalent vaccine.
Scenario 3	Applying the current vaccination rate and increasing trend of the rate.
Scenario 4	Expansion of the vaccination age to the WHO’s recommended age (9-14-years-old girls).
Scenario 4	Applying the current vaccination rate and increasing the trend of the rate.

HPV, human papillomavirus; WHO, World Health Organization.

^a) Specific statistics of vaccination rates are listed in S1 and S2 Tables.

Table 2.

Predicted cervical cancer incidences and PIFs for different vaccination scenarios in South Korea (2021-2024)

	2021-2025			2026-2030			2031-2035			2036-2040
	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)
Scenario 1
Crude	15,562	11.994	-	14,405	11.208	-	13,802	10.788	-	13,562	10.693	-
Standardized		8.491	-		8.057	-		7.923	-		8.011	-
Scenario 2
Crude	15,556	11.990	0.03 (–2.19 to 2.26)	14,355	11.169	0.35 (–1.96 to 2.65)	13,599	10.629	1.47 (–0.86 to 3.80)	13,003	10.252	4.13 (1.82 to 6.43)
Standardized		8.485	0.08 (–2.56 to 2.72)		7.994	0.79 (–1.92 to 3.50)		7.667	3.24 (0.56 to 5.93)		7.307	8.79 (6.23 to 11.36)
Scenario 3
Crude	15,555	11.989	0.04 (–2.18 to 2.26)	14,343	11.160	0.43 (–1.87 to 2.73)	13,550	10.591	1.83 (–0.50 to 4.15)	12,867	10.148	5.13 (2.84 to 7.42)
Standardized		8.483	0.09 (–2.54 to 2.73)		7.978	0.98 (–1.72 to 3.68)		7.604	4.03 (1.36 to 6.70)		7.14	10.93 (8.41 to 13.46)
Scenario 4
Crude	15,485	11.935	0.49 (–1.72 to 2.71)	14,111	10.979	2.04 (–0.23 to 4.32)	13,069	10.215	5.31 (3.05 to 7.58)	12,180	9.604	10.19 (7.99 to 12.39)
Standardized		8.411	0.95 (–1.67 to 3.57)		7.745	3.87 (1.23 to 6.52)		7.136	9.94 (7.39 to 12.48)		6.524	18.57 (16.21 to 20.93)

Scenario 1: without national vaccination program; Scenario 2: current national vaccination program; Scenario 3: use of nine-valent vaccine; Scenario 4: expansion of vaccination age. CI, confidence interval; PIF, potential impact fraction.

Table 3.

Predicted cervical cancer incidences and PIFs by Korean vaccination scenarios in 20s-30s (2021-2040)

	2021-2025			2026-2030			2031-2035			2036-2040
	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)
Scenario 1
Crude	2,918	9.321	-	2,566	8,759	-	2,247	8.286	-	1,857	7.706	-
Standardized		8.662	-		7.670	-		7.078	-		6.796	-
Scenario 2
Crude	2,913	9.304	0.17 (–4.95 to 5.30)	2,516	8.591	1.92 (–3.47 to 7.31)	2,045	7.540	9.01 (3.56 to 14.46)	1,297	5.385	30.12 (25.16 to 35.07)
Standardized		8.643	0.22 (–5.09 to 5.54)		7.467	2.65 (–3.08 to 8.38)		6.249	11.71 (5.95 to 17.48)		4.519	33.51 (28.42 to 38.61)
Scenario 3
Crude	2,912	9.300	0.22 (–4.91 to 5.34)	2,504	8.550	2.39 (–2.98 to 7.76)	1,996	7.358	11.20 (5.85 to 16.55)	1,161	4.820	37.45 (32.86 to 42.03)
Standardized		8.638	0.28 (–5.03 to 5.59)		7.417	3.30 (–2.41 to 9.00)		6.047	14.56 (8.93 to 20.19)		3.965	41.67 (37.01 to 46.32)
Scenario 4
Crude	2,842	9.077	2.61 (–2.42 to 7.64)	2,272	7.758	11.43 (6.43 to 16.43)	1,516	5.588	32.57 (28.17 to 36.96)	721	2.992	61.17 (57.83 to 64.51)
Standardized		8.403	3.00 (–2.21 to 8.20)		6.661	13.15 (7.88 to 18.42)		4.534	35.95 (31.36 to 40.53)		2.612	61.56 (58.03 to 65.10)

REFERENCES

1. National Cancer Institution. Cervical cancer treatment [Internet]. Bethesda, MD: National Cancer Institution; c2022. [cited 2022 Sep 12]. Available from: https://www.cancer.gov/types/cervical/patient/cervical-treatment-pdq#section/all
2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. Article PubMed PDF
3. Korea Central Cancer Registry; National Cancer Center. Annual report of cancer statistics in Korea in 2020: National Cancer Control Project [Internet]. Goyang: National Cancer Cancer; c2022. [cited 2023 Mar 12]. Available from: http://ncc.re.kr/cancerStatsList.ncc?searchKey=total&searchValue=&pageNum=1
4. Korean Statistical Information Service. Cause of death statistics [Internet]. Daejeon: Statistics Korea; c2023. [cited 2023 Mar 12]. Available from: https://kosis.kr/statHtml/statHtml.do?orgId=101&tblId=DT_1B34E09&vw_cd=MT_ZTITLZ&list_id=F_27&seqNo=&lang_mode=ko&language=kor&obj_var_id=&itm_id=&conn_papa=MT_ZTITLE
5. Castellsague X, Bosch FX, Munoz N, Meijer CJ, Shah KV, de Sanjose S, et al. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med. 2002;346:1105–12. Article PubMed
6. Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst. 1995;87:796–802. PubMed
7. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9. Article PubMed
8. Stewart BW, Wild CP. World cancer report 2014. Chapter 5.12. Cancers of the female reproductive organ. Geneva: World Health Organization; 2014. p. 465–82.
9. Kessler TA. Cervical cancer: prevention and early detection. Semin Oncol Nurs. 2017;33:172–83. Article PubMed
10. Munoz N, Castellsague X, Berrington de Gonzalez A, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006;24 Suppl 3:S3/1–10.
11. National Cancer Institute. Cervical cancer prevention (PDQ): health professional version [Internet]. Bethesda, MD: National Cancer Institute; c2023. [cited 2023 Apr 10]. Available from: https://www.cancer.gov/types/cervical/hp/cervical-prevention-pdq
12. World Health Organization. Electronic address swi. Human papillomavirus vaccines: WHO position paper, May 2017-Recommendations. Vaccine. 2017;35:5753–5. Article PubMed
13. World Health Organization. Cervical cancer [Internet]. Geneva: World Health Organization; c2022. [cited 2022 Oct 8]. Available from: https://www.who.int/news-room/fact-sheets/detail/cervical-cancer
14. Gearhart PA, Randall TC, Buckley RM Jr. Human papillomavirus (HPV) clinical presentation [Internet]. New York: Medscape; c2020. [cited 2022 Dec 8]. Available from: https://emedicine.medscape.com/article/219110-clinical
15. Petrosky E, Bocchini JA Jr, Hariri S, Chesson H, Curtis CR, Saraiya M, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015;64:300–4. PubMed PMC
16. Meeting of the Strategic Advisory Group of Experts on immunization, April 2014: conclusions and recommendations. Wkly Epidemiol Rec. 2014;89:221–36. PubMed
17. Kreimer AR, Sampson JN, Porras C, Schiller JT, Kemp T, Herrero R, et al. Evaluation of durability of a single dose of the bivalent HPV vaccine: the CVT trial. J Natl Cancer Inst. 2020;112:1038–46. Article PubMed PMC PDF
18. Basu P, Malvi SG, Joshi S, Bhatla N, Muwonge R, Lucas E, et al. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study. Lancet Oncol. 2021;22:1518–29. Article PubMed PMC
19. Barnabas RV, Brown ER, Onono MA, Bukusi EA, Njoroge B, Winer RL, et al. Efficacy of single-dose HPV vaccination among young African women. NEJM Evid. 2022;1:EVIDoa2100056.PubMed PMC
20. World Health Organization. Meeting of the strategic advisory group of experts on immunization, April 2022: conclusions and recommendations. Wkly Epidemiol Rec. 2022;97:261–76.
21. Shin HR, Won YJ, Jung KW, Kong HJ, Yim SH, Lee JK, et al. Nationwide cancer incidence in Korea, 1999~2001; first result using the national cancer incidence database. Cancer Res Treat. 2005;37:325–31. Article PubMed PMC
22. Oh CM, Won YJ, Jung KW, Kong HJ, Cho H, Lee JK, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2013. Cancer Res Treat. 2016;48:436–50. Article PubMed PMC PDF
23. Berman TA, Schiller JT. Human papillomavirus in cervical cancer and oropharyngeal cancer: one cause, two diseases. Cancer. 2017;123:2219–29. Article PubMed PDF
24. Kim YT, Serrano B, Lee JK, Lee H, Lee SW, Freeman C, et al. Burden of Human papillomavirus (HPV)-related disease and potential impact of HPV vaccines in the Republic of Korea. Papillomavirus Res. 2019;7:26–42. Article PubMed PMC
25. Arbyn M, Xu L. Efficacy and safety of prophylactic HPV vaccines. A Cochrane review of randomized trials. Expert Rev Vaccines. 2018;17:1085–91. Article PubMed
26. Centers for Disease Control and Prevention. Human papillomavirus (HPV): vaccine information for young women [Internet]. Atlanta, GA: Centers for Disease Control and Prevention; c2022. [cited 2022 Dec 20]. Available from: https://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young-women.htm
27. Antoni S, Soerjomataram I, Moller B, Bray F, Ferlay J. An assessment of GLOBOCAN methods for deriving national estimates of cancer incidence. Bull World Health Organ. 2016;94:174–84. Article PubMed PMC
28. Ahmad OB, Boschi-Pinto C, Lopez AD, Murray CJ, Lozano R, Inoue M. Age standardization of rates: a new WHO standard. GPE Discussion Paper Series, No. 31. EIP/GPE/EBD. Geneva: World Health Organization; 2001.
29. Hildebrandt M, Bender R, Gehrmann U, Blettner M. Calculating confidence intervals for impact numbers. BMC Med Res Methodol. 2006;6:32.Article PubMed PMC PDF
30. Olsen CM, Wilson LF, Green AC, Biswas N, Loyalka J, Whiteman DC. How many melanomas might be prevented if more people applied sunscreen regularly? Br J Dermatol. 2018;178:140–7. Article PubMed PDF
31. Ren X, Qiu L, Ke W, Zou H, Liu A, Wu T. Awareness and acceptance of HPV vaccination for condyloma acuminata among men who have sex with men in China. Hum Vaccin Immunother. 2022;18:2115267.Article PubMed PMC
32. World Health Organization. Vaccine in national immunization programme update [Internet]. Geneva: World Health Organization; c2020. [cited 2022 Oct 4]. Available from: https://cdn.who.int/media/docs/default-source/immunization/hpv/vaccineintrostatus.pdf?sfvrsn=a705e49c_
33. Gertig DM, Brotherton JM, Budd AC, Drennan K, Chappell G, Saville AM. Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. BMC Med. 2013;11:227.Article PubMed PMC PDF
34. Powell SE, Hariri S, Steinau M, Bauer HM, Bennett NM, Bloch KC, et al. Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions. Vaccine. 2012;31:109–13. Article PubMed
35. Cuschieri K, Kavanagh K, Cameron R, Bhatia R, Pollock KG. The massive decline of clinically relevant high-risk human papillomavirus (HR-HPV) infection in Scotland. In: Microbiology Society Annual Conference; 2017 Apr 3-6; Edinburgh, UK.
36. Tabrizi SN, Brotherton JM, Kaldor JM, Skinner SR, Liu B, Bateson D, et al. Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study. Lancet Infect Dis. 2014;14:958–66. Article PubMed
37. Ekwunife OI, O’Mahony JF, Gerber Grote A, Mosch C, Paeck T, Lhachimi SK. Challenges in cost-effectiveness analysis modelling of HPV vaccines in low- and middle-income countries: a systematic review and practice recommendations. Pharmacoeconomics. 2017;35:65–82. Article PubMed PMC PDF
38. World Health Organization (WHO). Global strategy to accelerate the elimination of cervical cancer as a public health problem [Internet]. Geneva: World Health Organization; c2020. [cited 2023 Apr 4]. Available from: https://www.who.int/publications/i/item/9789240014107
39. Brotherton JM, Tabrizi SN, Phillips S, Pyman J, Cornall AM, Lambie N, et al. Looking beyond human papillomavirus (HPV) genotype 16 and 18: defining HPV genotype distribution in cervical cancers in Australia prior to vaccination. Int J Cancer. 2017;141:1576–84. Article PubMed PDF
40. Wnukowski-Mtonga P, Jayasinghe S, Chiu C, Macartney K, Brotherton J, Donovan B, et al. Scientific evidence supporting recommendations on the use of the 9-valent HPV vaccine in a 2-dose vaccine schedule in Australia. Commun Dis Intell (2018). 2020;44:1–12. Article
41. Phillips A, Patel C, Pillsbury A, Brotherton J, Macartney K. Safety of human papillomavirus vaccines: an updated review. Drug Saf. 2018;41:329–46. Article PubMed PDF
42. Garland SM. The Australian experience with the human papillomavirus vaccine. Clin Ther. 2014;36:17–23. Article PubMed
43. Sinka K, Kavanagh K, Gordon R, Love J, Potts A, Donaghy M, et al. Achieving high and equitable coverage of adolescent HPV vaccine in Scotland. J Epidemiol Community Health. 2014;68:57–63. Article PubMed
44. Chido-Amajuoyi OG, Talluri R, Wonodi C, Shete S. Trends in HPV vaccination initiation and completion within ages 9-12 years: 2008-2018. Pediatrics. 2021;147:e2020012765Article PubMed PMC PDF
45. Toh ZQ, Russell FM, Reyburn R, Fong J, Tuivaga E, Ratu T, et al. Sustained antibody responses 6 years following 1, 2, or 3 doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent Fijian girls, and subsequent responses to a single dose of bivalent HPV vaccine: a prospective cohort study. Clin Infect Dis. 2017;64:852–9. Article PubMed PDF
46. Lee EH, Um TH, Chi HS, Hong YJ, Cha YJ. Prevalence and distribution of human papillomavirus infection in Korean women as determined by restriction fragment mass polymorphism assay. J Korean Med Sci. 2012;27:1091–7. Article PubMed PMC PDF
47. Lee SY, Lee JE, Gi MG, Kang C. An overview of immunization and efficacy of human papillomavirus vaccines. Public Health Wkly Rep. 2014;7:1162–6.
48. Comprehensive cervical cancer control: a guide to essential practice. 2nd ed. [Internet]. Geneva: World Health Organization; c2014. [cited 2020 Oct 15]. Available from: https://www.who.int/publications/i/item/9789241548953

Figure & Data

REFERENCES

Citations

Citations to this article as recorded by

PubReader
ePub Link

Cite

CITE: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Predicted Cervical Cancer Prevention: Impact of National HPV Vaccination Program on Young Women in South Korea

Cancer Res Treat. 2024;56(3):898-908. Published online January 15, 2024

DOI: https://doi.org/10.4143/crt.2023.981

XML Download

Abstract
Introduction
Materials and Methods
Results
Discussion
Electronic Supplementary Material
NOTES
REFERENCES

Predicted Cervical Cancer Prevention: Impact of National HPV Vaccination Program on Young Women in South Korea

Fig. 1. Trends of observed and predicted cervical cancer incidence under the scenarios for HPV national vaccination program. ASR, age-standardized incidence rate; CR, crude rate; HPV, human papillomavirus.

Fig. 2. Trends of potential impact fractions with 95% confidence intervals by HPV vaccination scenarios in South Korea (2021-2040). 2: scenario for current national vaccination program; 3: scenario for use of nine-valent vaccine; 4: scenario for expansion of vaccination age. HPV, human papillomavirus.

Fig. 3. Trends of potential impact fractions with 95% confidence intervals by HPV vaccination scenarios in 20s-30s in South Korea (2021-2040). 2: scenario for current national vaccination program; 3: scenario for use of nine-valent vaccine; 4: scenario for expansion of vaccination age. HPV, human papillomavirus.

Fig. 1.

Fig. 2.

Fig. 3.

Predicted Cervical Cancer Prevention: Impact of National HPV Vaccination Program on Young Women in South Korea

Scenario name	Description
Scenario 1	Assuming that the HPV national vaccination program has not been implemented.
Scenario 2	Current HPV national vaccination program and vaccination rate.^a)
Scenario 2	Applying the increasing trend of vaccination rates for girls born in 2005 and after.
Scenario 3	Only 9-valent vaccine was used instead of the current bivalent or tetravalent vaccine.
Scenario 3	Applying the current vaccination rate and increasing trend of the rate.
Scenario 4	Expansion of the vaccination age to the WHO’s recommended age (9-14-years-old girls).
Scenario 4	Applying the current vaccination rate and increasing the trend of the rate.

	2021-2025			2026-2030			2031-2035			2036-2040
	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)
Scenario 1
Crude	15,562	11.994	-	14,405	11.208	-	13,802	10.788	-	13,562	10.693	-
Standardized		8.491	-		8.057	-		7.923	-		8.011	-
Scenario 2
Crude	15,556	11.990	0.03 (–2.19 to 2.26)	14,355	11.169	0.35 (–1.96 to 2.65)	13,599	10.629	1.47 (–0.86 to 3.80)	13,003	10.252	4.13 (1.82 to 6.43)
Standardized		8.485	0.08 (–2.56 to 2.72)		7.994	0.79 (–1.92 to 3.50)		7.667	3.24 (0.56 to 5.93)		7.307	8.79 (6.23 to 11.36)
Scenario 3
Crude	15,555	11.989	0.04 (–2.18 to 2.26)	14,343	11.160	0.43 (–1.87 to 2.73)	13,550	10.591	1.83 (–0.50 to 4.15)	12,867	10.148	5.13 (2.84 to 7.42)
Standardized		8.483	0.09 (–2.54 to 2.73)		7.978	0.98 (–1.72 to 3.68)		7.604	4.03 (1.36 to 6.70)		7.14	10.93 (8.41 to 13.46)
Scenario 4
Crude	15,485	11.935	0.49 (–1.72 to 2.71)	14,111	10.979	2.04 (–0.23 to 4.32)	13,069	10.215	5.31 (3.05 to 7.58)	12,180	9.604	10.19 (7.99 to 12.39)
Standardized		8.411	0.95 (–1.67 to 3.57)		7.745	3.87 (1.23 to 6.52)		7.136	9.94 (7.39 to 12.48)		6.524	18.57 (16.21 to 20.93)

	2021-2025			2026-2030			2031-2035			2036-2040
	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)	No. of cases	Rate (×100,000)	PIF (%) (95% CI)
Scenario 1
Crude	2,918	9.321	-	2,566	8,759	-	2,247	8.286	-	1,857	7.706	-
Standardized		8.662	-		7.670	-		7.078	-		6.796	-
Scenario 2
Crude	2,913	9.304	0.17 (–4.95 to 5.30)	2,516	8.591	1.92 (–3.47 to 7.31)	2,045	7.540	9.01 (3.56 to 14.46)	1,297	5.385	30.12 (25.16 to 35.07)
Standardized		8.643	0.22 (–5.09 to 5.54)		7.467	2.65 (–3.08 to 8.38)		6.249	11.71 (5.95 to 17.48)		4.519	33.51 (28.42 to 38.61)
Scenario 3
Crude	2,912	9.300	0.22 (–4.91 to 5.34)	2,504	8.550	2.39 (–2.98 to 7.76)	1,996	7.358	11.20 (5.85 to 16.55)	1,161	4.820	37.45 (32.86 to 42.03)
Standardized		8.638	0.28 (–5.03 to 5.59)		7.417	3.30 (–2.41 to 9.00)		6.047	14.56 (8.93 to 20.19)		3.965	41.67 (37.01 to 46.32)
Scenario 4
Crude	2,842	9.077	2.61 (–2.42 to 7.64)	2,272	7.758	11.43 (6.43 to 16.43)	1,516	5.588	32.57 (28.17 to 36.96)	721	2.992	61.17 (57.83 to 64.51)
Standardized		8.403	3.00 (–2.21 to 8.20)		6.661	13.15 (7.88 to 18.42)		4.534	35.95 (31.36 to 40.53)		2.612	61.56 (58.03 to 65.10)

Table 1. Summary and descriptions of vaccination scenarios

HPV, human papillomavirus; WHO, World Health Organization.

Specific statistics of vaccination rates are listed in S1 and S2 Tables.

Table 2. Predicted cervical cancer incidences and PIFs for different vaccination scenarios in South Korea (2021-2024)

Table 3. Predicted cervical cancer incidences and PIFs by Korean vaccination scenarios in 20s-30s (2021-2040)