
==== Front
Hum Vaccin Immunother
Hum Vaccin Immunother
Human Vaccines & Immunotherapeutics
2164-5515
2164-554X
Taylor & Francis

39288789
10.1080/21645515.2024.2400750
2400750
Version of Record
Research Article
HPV
Factors influencing HPV vaccine hesitancy among university students in China: A cross-sectional survey utilizing the 3Cs model
Y. HE ET AL.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
He Yuancheng a b
Zhang Xiuqing c
Li Jie b d
Chen Yuehua b d
Zhang Lin e
https://orcid.org/0000-0002-3887-9079
Wei Yuehong b e
a School of Public Health, Sun Yat-sen University , Guangzhou, China
b Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention , Guangzhou, China
c Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, China
d School of Public Health, Guangzhou Medical University , Guangzhou, China
e Department of Parasite and Endemic Disease Prevention and Control, Guangzhou Center for Disease Control and Prevention , Guangzhou, China
CONTACT Yuehong Wei wei_yh0928@163.com Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Haizhu District, Guangzhou, Guangdong Province 510440, China.
17 9 2024
2024
17 9 2024
20 1 2400750Integra13 9 2024
Integra13 9 2024
22 5 2024
29 8 2024
02 9 2024
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
2024
The Author(s)
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 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. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

ABSTRACT

The HPV vaccine, which has been demonstrated to be an effective method of reducing the risk of developing cervical cancer, is still being underutilized among college students in China. To assess the current status of HPV vaccine hesitancy among college students in Guangdong Province after the COVID-19 outbreak, and to systematically analyze the influencing factors of HPV vaccine hesitancy and construct a prediction model based on the WHO 3Cs model. A cross-sectional web-based survey was conducted in June 2023 among female college students in four cities in Guangdong Province. The data were analyzed using binary logistic regression with a focus on the 3Cs model: Complacency, Convenience, and Confidence. LASSO regression was employed to analyze the variables deemed to be of significance and to construct predictive models. Out of 1399 participants, 86.5% expressed no hesitancy toward HPV vaccination. However, 11.9% exhibited hesitancy, and 1.6% refused vaccination altogether. Factors such as trust in vaccine efficacy, perception of HPV infection risk, price considerations, and constraints like distance or time were significant contributors to hesitancy. Knowledge of the HPV vaccine, socio-demographic characteristics, and the educational level of participants’ mothers also played a role in vaccine hesitancy. It is recommended that targeted interventions be implemented within educational institutions with the aim of raising awareness of cervical cancer and HPV vaccines, simplifying the scheduling of vaccination appointments, and increasing affordability through the implementation of strategic purchasing measures or subsidy schemes.

KEYWORDS

HPV vaccine
hesitancy
influencing factors
3Cs model
university students
The Basic Research Project of Key Laboratory of Guangzhou 202102100001 The Key Project of Medicine Discipline of Guangzhou 2021–2023-11 The work was supported by  The Basic Research Project of Key Laboratory of Guangzhou [202102100001]; The Key Project of Medicine Discipline of Guangzhou [2021–2023-11].
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pmcIntroduction

Cervical cancer stands as a prevalent malignancy affecting females globally, wherein the presence of persistent human papillomavirus (HPV) infection is deemed a crucial etiological factor.1 Cervical cancer incidence demonstrates significant geographical disparity, with Eastern Africa (including Zimbabwe) exhibiting the highest rates and Western Asia displaying the lowest. It is the second most common cancer in women in the South-East Asia region and is a significant contributor to cancer-related mortality, particularly in low- and middle-income countries (LMICs) such as Nepal.2 The findings of a meta-analysis encompassing epidemiological studies published between January 2000 and June 2018, focusing on high-risk human papillomaviruses (HPVs) in mainland Chinese women, revealed an overall infection rate of 19.0% (95% confidence interval, 17.1%-20.9%).3 Between 2005 and 2015, there was a consistent upward trend observed in the standardized mortality rate of cervical cancer among women in China, including both urban and rural areas. The average annual growth rate of the standardized mortality rates for women in China and urban areas was calculated to be 6.9% and 7.8% respectively.4 In the period 1990–2019, Cervical cancer continues to prevail as the primary cause of mortality among gynecologic malignancies in the female population of China.5 In 2020, Mainland China incurred a substantial economic burden of approximately 18.03 billion yuan attributed to HPV-related diseases, with cervical cancer alone accounting for 9.69 billion yuan.6 The findings underscored a substantial epidemiological and economic burden, further probably exacerbated by a decreasing age of onset among cervical cancer patients. Therefore, scaling up HPV vaccination programs is imperative to mitigate the economic losses associated with these diseases.6,7

The effectiveness of the HPV vaccine in cervical cancer prevention has been extensively demonstrated on a global scale, making it a highly cost-effective and life-saving preventive measure.8 The World Health Organization (WHO), recognizing its immense potential, strongly endorses and recommends the widespread administration of the HPV vaccine as a crucial component of comprehensive cervical cancer prevention strategies.9 In July 2016, the National Medical Products Administration (NMPA) granted regulatory authorization for the initial introduction of an HPV vaccine into the Chinese market. This specific vaccine, a privately-funded bivalent HPV vaccine, was specifically indicated for women aged 9–4510 years. Subsequently, the NMPA also endorsed the utilization of quadrivalent HPV vaccines for individuals aged 20–45 years and 9-valent HPV vaccines for women aged 16–26 years.11 On December 31, 2019, the NMPA issued an official announcement regarding the marketing approval of the first domestically developed HPV vaccine in China. Furthermore, in November 2020,12 the NMPA revised their guidelines to lower the minimum age requirement for quadrivalent vaccines to 9 years. Additionally, as part of efforts to enhance vaccination rates, an increasing number of cities in China have initiated the provision of complimentary domestically-produced bivalent HPV vaccines to adolescent groups. These initiatives aim to effectively promote the uptake of HPV vaccination nationwide. However, despite this regulatory approval, the vaccination rate has remained suboptimal. Specifically, among the targeted demographic of female university students, reported HPV vaccination rates have ranged from as low as 2.9% to a maximum of 34.2%.13–15

Vaccine hesitancy is defined as the reluctance or refusal to accept vaccination services, despite their availability,16 which had been identified by the WHO as one of the ten major global health threats even prior to the onset of the COVID-19 pandemic.17 In recent times, there has been a surge in reports of a decrease in the HPV vaccination rate in several countries, including Switzerland,18 America,19 Japan,20 and South Africa,21 attributed to vaccine hesitancy toward the HPV vaccine. Hence, conducting an in-depth analysis of the determinants impacting HPV vaccine hesitancy can contribute to mitigating hesitancy and fostering greater acceptance of vaccination. Additionally, this exploration can aid in the development of targeted interventions and strategies aimed at addressing and overcoming vaccine hesitancy barriers.

Multiple previous research investigations have predominantly focused on assessing levels of awareness regarding cervical cancer and the HPV vaccine, as well as gauging the inclination toward vaccination, in order to ascertain the perspectives of university students in various provinces and cities in China regarding HPV vaccines.12–15 However, there has been limited research directly measuring HPV vaccine hesitancy, with a prevalence rate of 37.57%22 observed among female university students. The prevalence of HPV vaccine refusal among university students, while not synonymous with vaccine hesitancy, exhibited a range of 11.55% to 43.1%.12–15,22–25 Guangdong Province is the most populous province in China,26 but no article has investigated the situation of HPV vaccine hesitancy and the reasons behind it among female college students in this province

In previous studies on HPV vaccination hesitancy, Behavioral models such as KAP (Knowledge, attitude and practices),27,28 Health Belief Model (HBM), and Theory of Planned Behavior (TPB)29 were mainly used in studying the factors that influence vaccination rates, each offering valuable insights into individual decision-making processes related to vaccination. The Strategic Advisory Group of Experts (SAGE) at the WHO proposed the 3Cs model in order to investigate the underlying factors of vaccine hesitancy. This model offers a comprehensive evaluation of the factors influencing vaccine hesitancy, which are classified into three key dimensions: complacency, convenience, and confidence.30 Complacency: An underestimation of disease risk or excessive confidence in preventive measures. Convenience: refers to the degree of access to vaccines, including physical and financial convenience. Confidence: The level of trust in the safety, effectiveness and recommendations of a vaccine. Compared with the traditional model, the 3Cs model focuses more on the specific behavior of vaccination, directly points out the key aspects affecting vaccine hesitation, and provides a more specific analytical framework for understanding and solving the problem of vaccine hesitation. The 3Cs model has gained significant traction among researchers as a valuable framework for analyzing vaccine hesitancy pertaining to COVID-19 and influenza.31,32 However, in previous studies in various provinces and cities in China, the use of HPV vaccine hesitancy was rare because most of them did not adopt a clear framework to analyze the influencing factors.12–15,22–25 Huang Yan used the 3Cs model for the first time to analyze the influencing factors of HPV vaccine hesitation among Chinese college students, but only Guangzhou, a city in Guangdong, was involved.13 Liangru Zhou conducted an online survey among Chinese medical students on HPV information sources and vaccine hesitancy, employing the World Health Organization (WHO) 3Cs model of vaccine hesitancy to evaluate respondents’ motivations for vaccine hesitancy.33 However, the study’s narrow focus on medical students limits its generalizability. Consequently, there is a notable scarcity of empirical data regarding the reluctance toward HPV vaccination and the factors influencing it among university students in Guangdong, particularly within the framework of multi-center studies with large sample sizes. During the COVID-19 epidemic, the majority of the Chinese population was vaccinated with the New Crown vaccine, which had a profound impact on public health awareness and vaccine attitudes, and may have influenced people’s attitudes and behaviors toward HPV vaccination.34

This study aimed to gain a comprehensive understanding of the current status of human papillomavirus (HPV) vaccine hesitancy among female university students in Guangdong Province following the outbreak of a novel coronavirus pneumonia (COVID-19) epidemic. We used the widely accepted 3Cs model developed by WHO to analyze in depth the determinants of HPV vaccine hesitancy. Although the traditional stepwise selection method is commonly used for variable selection in disease research,35–38 it is prone to the problem of overfitting.39 In contrast, LASSO (Least Absolute Shrinkage and Selection Operator) regression, a modern statistical method proposed by statistician Robert Tibshirani in 1996, is able to effectively deal with a large number of potential predictors and filter out the variables that are most relevant to the outcome.40 On this basis, we chose to combine LASSO regression and binary logistic regression to construct a model capable of predicting HPV vaccine hesitancy. Our underlying hypothesis is that HPV vaccine hesitancy is strongly associated with three key factors described in the 3Cs model: complacency, confidence and convenience. By exploring these underlying factors in depth, we aim to provide an empirical basis and strategic support for understanding and responding to HPV vaccine hesitancy.

Methods

Study design

This study utilized a comprehensive and rigorous multicenter cross-sectional research methodology, combined with a survey-based approach. The explanatory factors examined in this research were derived from the theoretical constructs of the well-established “3Cs” model. The primary outcome measure focused on the intention/hesitancy toward receiving HPV vaccination. In order to ensure the inclusion of relevant participants, the following eligibility criteria were implemented: (1) active enrollment as a student, either at the undergraduate or graduate level, in a designated university; (2) attainment of legal adulthood, i.e., 18 years of age or older; (3) identification as female; (4) possession of Internet access through a computer or smartphone; and (5) provision of informed consent.

Survey assessment tools

The survey assessment tools, devised by the research team, encompassed items pertaining to HPV vaccine hesitancy, determinants derived from the vaccine hesitancy “3Cs” model, HPV vaccine knowledge, and socio-demographic factors. The item evaluating vaccine hesitancy, “Please indicate your inclination to receive the HPV vaccine given your present circumstances,” provided respondents with the option to select one of the following responses: “complete acceptance,” “hesitancy,” or “declination. ” To measure participants’ attitudes toward complacency, convenience, and confidence, eleven questions were developed based on the “3Cs” factors (Table 1). In order to make a assessment of participants’ knowledge regarding HPV and the HPV vaccine, a set of nine questions was designed to evaluate their cognitive understanding. Furthermore, socio-demographic variables were formulated to collect individual data, encompassing age, university affiliation, field of study, educational attainment, individual living expenses, parental educational background, family cancer history, permanent residence address, and primary family medical insurance coverage, among other factors. It is important to emphasize that personal identifiers such as telephone numbers, e-mails, and names were not collected in the survey in order to protect the confidentiality of the participants. Prior to the main survey, a pilot study was conducted with 132 students to assess the readability and comprehension of the questionnaire, which confirmed that the questionnaire was easy to understand. The survey was conducted utilizing Wenjuanxing, an online survey tool, as the administration platform. The questionnaire used in this study is a well-established tool, so no additional validation was performed.Table 1. Measuring “3Cs” factors in survey instrument: utilized questionnaire items.

Factors	Questions	Question Design	
Complacency	What do you think of the severity of being infected by HPV?
What do you think of the probability of being infected by HPV?
How do you fear of being infected by HPV?
What do you think of the necessity of HPV vaccination?	Five-point Likert scale (“very low” to “very high”)	
Confidence	What do you think of the efficacy of vaccines?
What do you think of the safety of vaccines abroad?
What do you think of the safety of domestic vaccines?
Do you agree that the vaccine-related advice provided by medical staffs is reliable?	
Have you heard the negative information about vaccines?	Binary (“yes” or “no”)	
Convenience	Do you agree that the price prevents you from vaccinating against HPV?
Do you agree that time/distance prevents you from vaccinating against HPV?	

Size of the sample and collection of data

In June 2023, Python 3.8 was used to randomly select four cities from the 21 prefectures that comprise Guangdong Province. These were Guangzhou City, as well as Shenzhen, Foshan, and Dongguan. All institutions in these four cities were then stratified according to whether they had a medical discipline or not. One institution with a medical discipline and one institution without a medical discipline were randomly selected as the target institutions in each city. This required a total of eight institutions to be sampled. Additionally, to ensure the diversity of the sample, the study population was selected to encompass different levels of education, including college, undergraduate, and postgraduate. Ultimately, the study population was expanded to encompass Shenzhen University and Shenzhen University of Vocational Technology in Shenzhen, South China Agricultural University and Sun Yat-sen University in Guangzhou, Foshan Institute of Vocational Technology and Foshan Institute of Science and Technology in Foshan, and Guangdong Medical University and Dongguan Polytechnic in Dongguan. These choices were made in order to guarantee the representativeness and scope of the study sample, thereby facilitating an effective investigation of the discrepancies between different regions and institutions in Guangdong Province.n=Z1−α/22∗P1−Pδ2

The sample size for the survey was determined a priori using the following formula: n = (Z21−α/2)^2 * p * (1-p)/ẟ^2. Here, p denotes the anticipated prevalence or positive rate of the survey, and n represents the required sample size, Z21−α/2 corresponds to the standard normal deviation of α (Z21−α/2 = 1.96 for an α error of 0.05). Among university students in mainland China, the prevalence of HPV vaccine uptake was reported to be 68.0%41 and 71.8%42 based on two recent meta-analyses encompassing a total of 31 studies. Considering these findings, this study employed a cautious methodology and assumed a conservative estimate of 70.0% for the rate of acceptance of the HPV vaccine. By employing a statistical approach, the calculated sample size (n) for each city was determined to be 322, based on rigorous calculations that took into account various factors. Therefore, the research aimed to include a total sample size of 1288 female university students from the four designated cities. The sample size was determined to achieve the desired level of statistical power and precision, allowing the study to detect significant differences or associations and to ensure the results are reliable and generalizable.

Data collection took place from 20 June to 26 July 2023, utilizing the Wenjuanxing online survey tool. To recruit participants, advertisements were placed in class announcements, ensuring a diverse sample. The electronic survey instrument’s landing page prominently displayed comprehensive study information and mandated participants to grant informed consent prior to advancing further. Only those who clicked the designated button, indicating their consent and willingness to participate, were able to access and complete the questionnaire.

To ensure data integrity, the online questionnaire was only considered valid if it took more than 120 seconds to complete and all required fields were filled in. By implementing these strict quality control measures, a total of 1,416 online questionnaires were successfully collected. After quality control, 1,399 valid questionnaires were recovered. During the quality control process, we also excluded questionnaires completed by male users and questionnaires where not all the content of the questionnaire had been completed. These stringent procedures were designed to ensure the credibility and accuracy of the data collected.

Statistical analysis

To ensure the reliability and accuracy of the data, we first exported the data and results collected from the online questionnaire background to Microsoft Excel files before importing the data into IBM SPSS 24.0 (IBM Corp, Armonk, NY, USA) for data analysis. Chi-square test and binary logistic regression analysis were used to examine the association between sociodemographic factors, 3Cs (confidence, complacency and convenience) and vaccine hesitancy. First, we use the chi-square test to determine the factors associated with a significant vaccine hesitant. “Accept without hesitation” was set as the reference group, and “hesitate” were set as the control group. Binary logistic regression analysis was used to explore the relationship between the independent variables and the attitude of college students to HPV vaccination, and the results were expressed as odds ratio (OR) and 95% confidence interval (CI). In this study, we employed the R statistical software, version 4.2.3, to perform LASSO regression for the purpose of selecting predictive variables. These were then incorporated into a binary logistic regression model, which was constructed for the purpose of developing a prediction model. A random selection was made of 70% of the data for use as the training set and 30% for use as the test set. Receiver operating characteristic (ROC) curves were drawn for both the training set and the test set in order to evaluate the performance of the model, and a calibration curve was also created. The level of statistical significance was determined with a p-value of less than 0.05. These analysis methods were used to comprehensively explore the factors influencing vaccine hesitancy among female college students in Guangdong.

Results

Demographic profile and knowledge regarding HPV vaccines

In the aggregate,1399 questionnaires were collected and deemed valid for analysis in this study. Table 2 displays the demographic characteristics of the female university students. Among the study participants who completed the questionnaire, 37.8% were aged below 20, 59.8% were aged between 20 and 25, and 2.4% were aged above 25. Furthermore, 95.6% of the participants were pursuing undergraduate degrees. In terms of academic backgrounds, 18.9% of the participants were majoring in medicine. Regarding financial aspects, 60.2% of the participants reported a monthly living expenses consumption ranging between CNY 1000 and 2000. Additionally, 38.2% of the students’ families resided in rural areas, 75.1% of student’s family bought insurance of primary medical treatment, 71.5% of the mothers had college or bachelor’s degree, and 85.1% had no family history of cancer. Regarding the level of knowledge pertaining to HPV vaccine and the cervical cancer, 63.5% of the participants obtained a moderate score, while 14.1% achieved a high score. Moreover, 70.9% of university students reported being advised or counseled by healthcare professionals regarding the human papillomavirus (HPV) vaccine, while 75.0% received recommendations from individuals in their social circle.Table 2. Demographic and HPV knowledge profile of university students across different levels of vaccine hesitancy.

Factors	 	Total(1399)
, n (%)	The Attitude to HPV Vaccination,
n (%)	p-Value	
Hesitancy
(n = 166)	No Hesitancy
(n = 1210)	
Age (years)	<20	529 (37. 8)	71 (42. 8)	452 (37. 4)	.254	
20–25	836 (59. 8)	93 (56. 0)	726 (60. 0)	
>25	34 (2. 4)	2 (1. 2)	32 (2. 6)	
College	1	183 (13. 1)	13 (7. 8)	167 (13. 8)	.422	
2	176 (12. 6)	18 (10. 8)	155 (12. 8)	
3	167 (11. 9)	18 (10. 8)	146 (12. 1)	
4	175 (12. 5)	24 (14. 5)	151 (12. 5)	
5	170 (12. 2)	23 (13. 9)	147 (12. 1)	
6	174 (12. 4)	22 (13. 3)	148 (12. 2)	
7	176 (12. 6)	22 (13. 3)	149 (12. 3)	
8	178 (12. 7)	26 (15. 7)	147 (12. 1)	
City	Guangzhou	359 (25. 7)	31 (18. 7)	322 (26. 6)	.157	
Dongguan	342 (24. 4)	42 (25. 3)	297 (24. 5)	
Shenzhen	344 (24. 6)	45 (27. 1)	295 (24. 4)	
Foshan	354 (25. 3)	48 (28. 9)	296 (24. 5)	
Major	Medicine	265 (18.9)	10 (6. 0)	254 (21. 0)	<.001	
Non-Medicine	1134 (81.1)	156 (94)	956 (79. 0)	
Education level	College or bachelor’s degree	1337 (95. 6)	159 (95. 8)	1157 (95. 6)	.923	
Graduate student or above	62 (4. 4)	7 (4. 2)	53 (4. 4)	
Living expense(CNY)	<1000	256 (18. 3)	35 (21. 1)	218 (18. 0)	.099	
1000–2000	842 (60. 2)	107 (64. 5)	722 (59. 7)	
2000–3000	224 (16.0)	20 (12. 0)	199 (16. 4)	
>3000	77 (5. 5)	4 (2. 4)	71 (5. 9)	
Education level of father	Junior high school and below	105(7. 5)	15(9. 0)	88(7. 3)	.084	
Technical secondary school or high school	443(31. 7)	64(38. 6)	367(30. 3)	
College or bachelor’s degree	763(54. 5)	80(48. 2)	674(55. 7)	
Graduate student or above	88(6. 3)	7(4. 2)	81(6. 7)	
Education level of mother	Junior high school and below	31(2. 2)	12(7. 2)	16(1. 3)	<.001	
Technical secondary school or high school	180(12. 9)	41(24. 7)	131(10. 7)	
College or bachelor’s degree	1000(71. 5)	102(61. 4)	888(73. 4)	
Graduate student or above	188(13. 4)	11(6. 6)	175(14. 5)	
Family history of cancer	No	1190 (85. 1)	153 (92. 2)	1016 (84. 0)	.006	
Yes	209 (14.9)	13 (7. 8)	194 (16. 0)	
Permanent home address	Urban	864 (61.8)	104 (62. 7)	750 (62. 0)	.868	
Rural	535 (38.2)	62 (37. 3)	460 (38. 0)	
Whether the family buys basic medical insurance	No	349 (24. 9)	57 (34. 3)	279 (23. 1)	.002	
Yes	1050 (75. 1)	109 (65. 7)	931 (76. 9)	
HPV and vaccine knowledge	Low scores (0–3)	314 (22. 4)	68 (41. 0)	235 (19. 4)	<.001	
Moderate scores (4–6)	888 (63. 5)	91 (54. 8)	817 (64. 9)	
High scores (7–9)	197(14. 1)	7 (4. 2)	190 (15. 7)	
Has your health care provider recommended the HPV vaccine	No	407 (29.1)	73 (44. 0)	319 (26. 4)	<.001	
Yes	992(70.9)	93 (56. 0)	891 (73. 6)	
Have friends recommended the HPV vaccine to you	No	350 (25.0)	67 (40. 4)	269 (22. 2)	<.001	
Yes	1049 (75. 0)	99 (59. 6)	941 (77. 8)	

Refusal (n = 20) was not shown in this table because few or no participants chose this option.

Vaccine hesitancy level

Among the female university student population, a significant majority of 1210 students (86.5%) expressed a willingness to receive the HPV vaccine without any hesitancy. A smaller proportion of 166 students (11.9%) exhibited vaccine hesitancy, while only 23 students (1.6%) outright refused to receive the HPV vaccine. It is noteworthy that of the 1,399 students, a total of 508 have been vaccinated or have scheduled appointments for vaccination, resulting in an overall vaccination rate of 36.3%. Of these, 487 have received the first dose and above, while 21 have scheduled appointments for vaccination but have not yet been vaccinated. The average age at first dose is 19.4 years. Table 2 presents the correlations between various sociodemographic factors and vaccine hesitancy. Notably, several sociodemographic factors demonstrated statistically significant relationships with vaccine hesitancy (p < .05). These factors include the students’ majors, the education level of their mothers, the presence or absence of a family history of cancer, whether the family purchased basic medical insurance, the students’ knowledge about HPV and the vaccine, as well as whether they had received recommendations for the HPV vaccine from individuals in their social circle or medical staff.

The cognitive and attitude regarding HPV vaccination

Comprehensive analysis of the 3 Cs factors in college students’ group distribution patterns and its correlation with vaccine hesitant results presented in Table 3. Significantly, most of the participants (74.6%) perceived cervical cancer as a highly detrimental health condition, emphasizing the severity of its impact. Furthermore, a significant proportion of students (87.7%) acknowledged the necessity of HPV vaccination in preventing cervical cancer. In terms of specific concerns, 41.1% of students expressed a heightened fear of cervical cancer, indicating their awareness of its potential risks. Additionally, 16.4% of the participants held the perception that they were more susceptible to HPV infection, demonstrating a recognition of personal susceptibility. Conversely, only a minority of students mentioned factors such as price (14.6%) or time/distance (10.4%) as potential barriers to HPV vaccination, suggesting that these practical considerations had influence on their decision-making process. Furthermore, a significant percentage of students (78.6%) indicated a lack of exposure to any adverse information concerning vaccines, and the majority of students demonstrated confidence in the effectiveness (86.5%) and safety (83.6%) of HPV vaccines, as well as the advice provided by medical staff (80.1%).Table 3. Chi-square results of 3Cs factors by hesitancy status.

 	Factors	Total, n (%)	The Attitude to HPV Vaccination, n (%)	p-Value	
Hesitancy	No Hesitancy
(n = 1210)	
(n = 166)	
Complacency	The severity of being infected by HPV	Mild	102(7. 4)	46(27. 7)	56(4. 6)	<.001	
Moderate	248(18. 0)	89(53. 6)	159(13. 1)	
Very severe	1026(74. 6)	31(18. 7	995(82. 2)	
The probability of being infected by HPV	Mild	206(15. 0)	67(40. 4)	139(11. 5)	<.001	
Moderate	945(68. 7)	90(54. 2)	855(70. 7)	
Very severe	225(16. 4)	9(5. 4)	216(17. 9)	
The fear of being infected by HPV	Mild	160(11. 6)	38(22. 9)	122(10. 1)	<.001	
Moderate	650(47. 2)	110(66. 3)	540(44. 6)	
Very severe	566(41. 1)	18(10. 8)	548(45. 3)	
The necessity of HPV vaccination	Mild	35(2. 5)	18(10. 8)	17(1. 4)	<.001	
Moderate	134(9. 7)	53(31. 9)	81(6. 7)	
Very severe	1207(87. 7)	95(57. 2)	1112(91. 9)	
Confidence	The negative information about vaccines	Yes	295(21. 4)	39(23. 5)	256(21. 2)	.491	
No	1081(78. 6)	127(76. 5)	954(78. 8)	
The safety of domestic vaccines	Distrust	61(4. 4)	17(10. 2)	44(3. 6)	<.001	
Neutral	133(9. 7)	36(21. 7)	97(8. 0)	
Trust	1182(85. 9)	113(68. 1)	1069(88. 3)	
The safety of vaccines abroad	Distrust	87(6. 3)	19(11. 4)	68(5. 6)	<.001	
Neutral	108(7. 8)	42(25. 3)	66(5. 5)	
Trust	1181(85. 8)	105(63. 3)	1210(88. 9)	
The efficacy of vaccines	Distrust	67(4. 9)	20(12. 0)	47(3. 9)	<.001	
Neutral	160(11. 6)	85(51. 2)	75(6. 2)	
Trust	1149(83. 5)	61(36. 7)	1088(89. 9)	
The vaccine-related advice provided by medical staffs is reliable	Distrust	91(6. 6)	26(15. 7)	65(5. 4)	<.001	
Neutral	183(13. 3)	58(34. 9)	125(10. 3)	
Trust	1102(80. 1)	82(49. 4)	1020(84. 3)	
Convenience	Price prevents from vaccinating against HPV	Yes	201(14. 6)	106(63. 9)	95(7. 9)	<.001	
No	1175(85. 4)	60(36. 1)	1115(92. 1)	
Time/distance prevents from vaccinating	Yes	143(10. 4)	79(47. 6)	64(5. 3)	<.001	
No	1233(89. 6)	87(52. 4)	798(94. 7)	

Significant associations (p < .05) were observed between vaccine hesitancy and the majority of the aforementioned characteristics. The results of our study revealed significant associations between lower levels of vaccine hesitancy and factors such as heightened fear of HPV infection, increased perception of susceptibility to HPV and its severity of harm, and a stronger perceived necessity for vaccination as a preventive measure. Furthermore, the receipt of a healthcare provider’s recommendation, along with a positive perception of the safety and effectiveness of HPV vaccination, exhibited significant associations with decreased levels of vaccine hesitancy.

On the other hand, practical considerations such as price and distance/time were significant hindrances to vaccination, indicating that these factors played a role in influencing vaccine hesitancy. However, our study did not find compelling evidence to support the notion that the influence and significance of encountering negative vaccine-related information played a remarkable role in shaping vaccine hesitancy among the university student population.

Factors influencing HPV vaccine hesitancy

Table 4 presents the findings of the binary logistic regression analysis, which examined the associations between various factors and HPV vaccine hesitancy based on the 3Cs model, revealing significant relationships. Firstly, students who held a perception of HPV infection consequences as serious demonstrated a higher likelihood of exhibiting unhesitant behavior toward vaccination (Trust: OR = 12.90, 95% CI: 4.74–35.09). Additionally, students who encounter fear associated with HPV infection are more inclined to exhibit reduced levels of vaccine hesitancy (High: OR = 3.04, 95% CI: 1.10–8.45). Thirdly, students who maintain the belief in the necessity of HPV vaccination demonstrate a higher likelihood of having no hesitation about vaccination (High: OR = 5.88, 95% CI: 1.61–21.52). Conversely, students who perceived the price of the vaccine as unacceptable (OR = 0.03, 95% CI: 0.01–0.06) and those who considered the time/distance as inconvenient (OR = 0.08, 95% CI: 0.04–0.17) were more likely to express hesitancy toward receiving the vaccine.Table 4. Binary logistic regression to identify factors associated with HPV vaccine hesitancy.

Factors	 	Hesitancy vs. No Hesitancy	
 	OR	95% Cl	p-Value	
3Cs	The severity of being infected by HPV	(Rf:distrust)	 	 	 	 	
Neutral	1. 23	0. 48	3. 20	.670	
Trust	12. 90	4. 74	35. 09	<.001	
The likelihood of HPV infection	(Rf: Low)	 	 	 	 	
Neutral	6. 35	2. 97	13. 56	<.001	
High	28. 11	6. 06	130. 53	<.001	
Fear of HPV infection	(Rf: Low)	 	 	 	 	
Neutral	0. 43	0. 19	0. 95	.040	
High	3. 04	1. 10	8. 45	.030	
The necessity for HPV vaccination	(Rf: Low)	 	 	 	 	
Neutral	1. 89	0. 46	7. 73	.370	
High	5. 88	1. 61	21. 52	.010	
Price prevents from vaccinating against HPV	(Rf: No)	 	 	 	 	
Yes	0. 03	0. 01	0. 06	<.001	
Time/distance prevents you from vaccinating against HPV	(Rf: No)	 	 	 	 	
Yes	0. 08	0. 04	0. 17	<.001	
Other	Education level of mother	(Rf:Junior high school and below)	 	 	 	 	
Technical secondary school or high school	2. 67	1. 13	6. 32	.025	
College or bachelor’s degree	6. 39	2. 85	14. 33	<.001	
Graduate student or above	13. 82	5. 11	37. 43	<.001	
Knowledge of HPV and HPV vaccine	(Rf: Low scores (0–3))	 	 	 	 	
Moderate scores(4–6)	2. 48	1. 74	3. 55	<.001	
High scores (7–9)	9. 23	3. 60	23. 63	<.001	

Furthermore, an elevated level of HPV and HPV vaccine-related knowledge was found to be positively associated with an increased probability of displaying non-hesitant behavior toward vaccination (High score: OR = 9.23, 95% CI: 3.60–23.63; Moderate: OR = 2.48, 95% CI: 1.74–3.55). Moreover, the maternal educational level exerted an influence on the extent of vaccine hesitancy, demonstrating that higher levels of education were associated with a reduced probability of exhibiting hesitation toward vaccination. Specifically, having a technical secondary school or high school education was associated with a decreased likelihood of hesitation (OR = 2.67, 95% CI: 1.13–6.32), while possessing a college or bachelor’s degree was found to be associated with a further reduction in vaccine hesitancy (OR = 6.39, 95% CI: 2.85–14.33). Furthermore, having a graduate or postgraduate education was associated with the highest decrease in vaccine hesitancy (OR = 13.82, 95% CI: 5.11–37.43). These findings suggest that higher maternal education levels are associated with a greater likelihood of the daughter being non-hesitant toward vaccination.

Through a comprehensive examination of the factors contributing to vaccine skepticism, we identified several key reasons, including inquiries regarding the safety and efficacy of the vaccine, apprehensions regarding potential side effects, and the perception of HPV vaccination as being financially burdensome. These results with the results of our 3Cs model is consistent, further verified the model to explain the effectiveness of the vaccine hesitant behavior. The distribution of reasons for hesitation to receive the HPV vaccine is shown in Figure 1, with 22.0% of all reasons being doubts about the safety and efficacy of the vaccine, 19.0% of all reasons being concerns about the side effects of the vaccine, and 3.0% being due to a history of previous allergies or contraindications to vaccination, which was the lowest percentage of all reasons. It is worth noting that 25.9% of students still did not know how to obtain information related to vaccination. This indicates that there is still a certain deficit in the dissemination of health information. Figure 1. Reasons for hesitancy toward HPV vaccination.

LASSO regression was used to screen out the following variables as predictors: Grade of score, Severity, Possibility, Fear, Necessity, Efficacy, Education level of mother, Family history of cancer, Living expense, Major, Price, Time or distance, Friend recommendation. These variables were then included in a binary logistic regression analysis to further assess their predictive significance. The results of this analysis were used to plot the nomogram shown in Figure 2. The ROC curve of the training set was drawn according to the above predictive variables, as shown in Figure 3, and the ROC curve of the test set was shown in Figure 4. The area under the curve of the training set was 0.973, while the area under the curve of the test was 0.979, indicating that the selected variables had predictive significance and the model had a high degree of fitting. In order to evaluate the prediction performance of the prediction model, we drew the calibration curve as shown in Figure 5, n = 963, mean absolute error = 0.01, mean square error = 0.0004, 0.9 quantile of absolute error = 0.038. In conclusion, the prediction performance of the model is good. Figure 2. Nomogram for predicting HPV vaccine hesitancy.

Figure 3. Training set ROC curve for HPy vaccine hesitancy.

Figure 4. Test set ROC curve for HPV vaccine hesitancy.

Figure 5. Nomogram for predicting HP vaccine hesitancy.

Discussion

This study employed the comprehensive WHO vaccine hesitancy 3Cs model as a framework to conduct a comprehensive examination of the extent of HPV vaccine hesitancy among university students in four cities within Guangdong province. Furthermore, the study undertook a systematic investigation of the various factors that influence vaccine hesitancy in this context. The results of a multi-center survey in Guangdong Province showed that more than 80.0% of female university students indicated that they were willing to receive HPV vaccination. These findings indicate a comparatively lower incidence of vaccine hesitancy and refusal when compared to previous studies conducted among Chinese university students in various provinces and cities, where rates ranged from 11.55% to 43.1%.12–15,25–28 Similarly, when compared to studies conducted among adult women in other countries, the recorded levels of vaccine hesitancy and refusal (ranging from 10.0% to 33.8%)23,43,44 were notably lower. Moreover, the level of acceptance for the HPV vaccination in this study was notably high, with 36.3% of female students having already received the vaccine or having scheduled an appointment for vaccination. These figures surpass the findings reported in previous studies.12–15 The results of our study indicate a significant correlation between the educational attainment of mothers and the extent of hesitancy regarding the HPV vaccine in their daughters. This implies that elevated levels of maternal education and awareness of the gravity of the disease are crucial determinants that facilitate maternal and infant HPV vaccination. It is therefore essential to give priority to health education and promotion initiatives aimed at mothers in order to guarantee the highest possible vaccination rates.45 It is notable that this multicenter survey represents the inaugural comprehensive investigation into the reluctance of Chinese female university students in Guangdong province toward receiving the HPV vaccine in the wake of the global health emergency caused by the SARS-CoV-2 pandemic. It is plausible that the global health crisis has influenced individuals’ perception of risk and their inclination to receive vaccination to a certain extent.46–49

In terms of confidence, our study revealed that medical staff, along with the safety and efficacy of the HPV vaccine, are perceived as highly confident by college students. This confidence extends to the belief that the HPV vaccine is safe, both at home and abroad. Previous research has consistently demonstrated that confidence is a crucial factor influencing vaccine hesitancy. Additionally, the safety and efficacy of vaccines are identified as paramount factors influencing individuals’ vaccination decisions.50 Notably, in contrast to previous findings,51 our study observed no statistically significant disparity in the impact of exposure to adverse news regarding vaccines affecting vaccine hesitancy. 75.6% considered the advice of friends and peers as an important source of information and could continue to play the important role of peer education in spreading knowledge and experience.52 Furthermore, it is essential to reinforce the capabilities of medical personnel in order to facilitate the dissemination of accurate information regarding diagnosis and treatment, as well as to provide guidance on the potential benefits and risks associated with cervical cancer and HPV vaccination.53

The influence of risk awareness on HPV vaccine hesitancy is evident in the complacency dimension. Individuals who demonstrate heightened concerns regarding cervical cancer, perceive themselves as more susceptible to HPV infection, perceive vaccination as highly necessary, and acknowledge the severe consequences of cervical cancer infection are more inclined to vaccinate without reluctance. This aligns with previous research findings.54 In light of the COVID-19 pandemic, there is an increased probability that the general public will demonstrate heightened risk awareness with regard to diseases with a high prevalence. It is therefore imperative to ensure that college students are adequately informed about cervical cancer and the HPV vaccine, and to enhance their understanding of the vaccine in order to mitigate any reluctance to be vaccinated. One strategy is to integrate comprehensive HPV education into existing health curricula at universities. This can entail the organization of informational sessions, workshops and seminars led by healthcare professionals to address common misconceptions about HPV infection and the safety of the vaccine. Furthermore, the establishment of peer education programs where vaccinated students share their experiences and correct misinformation among their peers can significantly influence vaccine acceptance. The utilization of social media platforms and university websites to disseminate accurate and accessible information about HPV and vaccination procedures can also enhance students’ knowledge and facilitate informed decision-making.

The results of the binary logistic regression analysis and chi-square test provide substantial evidence that the convenience dimension significantly hinders vaccination against HPV among university students residing in Guangdong province. In particular, both cost and accessibility (as gauged in terms of time or distance) were identified as significant impediments to vaccination. In order to address these challenges, it is essential to implement strategic recommendations. The recent introduction of complimentary domestically-produced two-valent HPV vaccines in various cities across China for teenagers represents a promising step toward alleviating the financial barrier associated with HPV vaccination. Nevertheless, extending this subsidy program to encompass university students could serve to enhance vaccine accessibility and uptake. Furthermore, the complex appointment process was identified as a significant deterrent to HPV vaccination, thereby underscoring the necessity to streamline appointment procedures in response to public demand. Implementing online appointment systems, mobile vaccination clinics on campuses, or extending clinic hours to accommodate student schedules represent practical strategies that could serve to significantly improve vaccination accessibility and convenience.

Moreover, based on the KAP model, the exposure to HPV-related information was found to have a significant impact on the acceptance of the HPV vaccine and the level of knowledge among young women in China.55 Nevertheless, despite this favorable correlation, a considerable disparity persists between the intention to be vaccinated and the actual act of vaccination, underscoring the necessity to address this discrepancy in public health initiatives. A review of the existing literature reveals a consistent pattern: the willingness or intention to vaccinate against HPV is generally higher than the actual uptake of the vaccine.4,25,44 This discrepancy underscores the necessity to comprehend and address the impediments that hinder individuals from translating their intentions into actions. A multitude of factors contribute to this disparity between intentions and behaviors. Firstly, people may have a perception of being at a low likelihood of acquiring HPV infection,4,25,44 leading to a sense of complacency and a decreased motivation to get vaccinated. This perception of low risk may be influenced by a lack of awareness about the prevalence and consequences of HPV infection, as well as misconceptions about its transmission and severity. Secondly, inadequate information and knowledge about HPV and the vaccines available can hinder vaccination uptake.4,25,44 The dissemination of misinformation or misconceptions regarding the efficacy and safety of vaccines can contribute to vaccine hesitancy or reluctance to receive vaccination. It is imperative to provide accurate and evidence-based information about HPV, the associated risks, and the benefits of vaccination in order to address these concerns. Additionally, concerns about the cost of the vaccines can act as a significant barrier.4,25,44 The high cost of HPV vaccines represents a significant barrier to access and affordability, thereby limiting the uptake of vaccinations. In order to overcome this obstacle, strategies that seek to improve the accessibility and affordability of vaccines should be given priority. This entails advocating for government subsidies and integrating HPV vaccines into national immunization programs. These measures are of the utmost importance in reducing financial obstacles and increasing vaccine accessibility across diverse socioeconomic groups. It is of the utmost importance to address the factors that influence vaccination intentions in order to bridge the gap between intentions and actual behavior. It is recommended that public health campaigns prioritize the dissemination of information regarding the risks associated with HPV, the debunking of misconceptions, and the promotion of vaccine efficacy and safety. It is imperative that efforts are made to ensure that vaccines are accessible to all individuals, irrespective of their socioeconomic status. It is recommended that future research be directed toward the elucidation of factors that facilitate the transition from vaccination intention to behavior. It is recommended that targeted interventions and strategies be developed to enhance the uptake of the HPV vaccine, with a particular focus on bolstering public confidence in the safety and efficacy of the vaccine. This necessitates the dissemination of accurate information in order to counteract misinformation effectively. Furthermore, research should investigate methods to enhance the knowledge and communication skills of healthcare professionals in conveying the importance and benefits of HPV vaccination. Evaluating the influence of social, cultural, family dynamics, and educational backgrounds on vaccination intentions is crucial for developing tailored intervention strategies for diverse population groups.

In this study, LASSO regression was used to select variables significantly associated with HPV vaccine hesitancy from a number of potential predictors, and the areas under the curve in the training and test sets were 0.973 and 0.979, respectively, indicating that the model had significant predictive power and goodness of fit. This study provides an in-depth analysis of several key factors influencing HPV vaccine hesitancy, providing an important basis for the development of personalized interventions and health policies. By identifying and understanding these factors, we can target and increase public acceptance of HPV vaccines and reduce hesitancy, thereby effectively preventing the onset and spread of HPV-related disease.

This study marks the inaugural comprehensive examination in Guangdong Province of vaccine hesitancy among college students and its associated determinants, employing the 3Cs model as the underlying framework. A stratified sampling approach was implemented, encompassing four cities exhibiting diverse levels of socioeconomic development, thereby guaranteeing an adequate sample size and favorable representativeness. However, several limitations should be acknowledged. Firstly, the utilization of online surveys may introduce selection bias, as it exclusively captures the viewpoints of college students who have an interest in the HPV vaccine. Those who are hesitant or uninterested in the vaccine may be less likely to participate, potentially leading to overestimation of vaccine acceptance rates. Secondly, the study employs a cross-sectional design, limiting its ability to establish causal relationships between influencing factors and HPV vaccine hesitancy, and instead focusing on identifying correlations. Longitudinal studies or experimental designs are needed to determine the causal links between specific factors and vaccine uptake behavior. Thirdly, A specific limitation of this study is that the multiple-choice questions within the questionnaire were not submitted for review by an ethics committee or external experts before being administered. This review process could have helped identify and mitigate potential biases introduced by the multiple-choice format, where respondents might be influenced by the provided options rather than freely expressing their true opinions. Additionally, In China, an appointment is typically required in advance for HPV vaccination. Given that Chinese university students hail from a multitude of global origins, they may select disparate hospitals or medical institutions for the administration of the vaccine. Consequently, our survey encountered challenges in acquiring information regarding the specific physicians associated with these students. Finally, it is notable that this study does not include data on compliance rates for non-vaccination measures or other non-HPV vaccines, which would have provided a more comprehensive understanding of the factors influencing HPV vaccination decisions. The inclusion of such controls would have furnished a more expansive context and permitted a more comprehensive understanding of the health behaviors that inform decisions regarding HPV vaccination. This limitation indicates that the findings should be interpreted with caution, particularly in regard to their generalizability to other vaccination contexts.Nevertheless, the study remains valid even in the absence of these controls, and provides valuable insights into HPV vaccine hesitancy. The research design was specifically tailored to examine the factors influencing HPV vaccination through the lens of the WHO 3Cs model (complacency, convenience, and confidence). By focusing on these key determinants, the study effectively identifies the unique barriers to HPV vaccination in the target population.The use of LASSO regression and binary logistic regression permitted a concentrated examination of the variables most pertinent to HPV vaccine hesitancy, thereby ensuring the robustness of the findings within this particular context. While broader controls could have augmented the study’s scope, the targeted approach facilitated a more profound understanding of the specific challenges associated with HPV vaccine uptake, which is vital for the development of targeted public health interventions.Future research should endeavor to incorporate controls for other vaccination behaviors in order to build upon these findings and provide a more comprehensive analysis. Notwithstanding these constraints, the study yields significant insights into the determinants of HPV vaccine hesitancy among female college students in Guangdong Province, furnishing valuable data for devising targeted intervention measures and strategies to enhance vaccine uptake rates.

Conclusions

The study initially revealed the prevalence of HPV vaccination hesitancy among female university students in Guangdong Province. Additionally, it was found that over 80% of the participants exhibited a positive attitude toward the HPV vaccine. In conjunction with the WHO’s 3Cs model, the study identified a number of pivotal factors influencing vaccine hesitancy, including perceived severity and likelihood of HPV infection, perceived necessity of the HPV vaccine, price of the vaccine, and convenience of vaccination. Furthermore, the study identified a significant correlation between students’ HPV-related knowledge scores and their mothers’ educational attainment.

It is recommended that efforts be made to improve the dissemination of cervical cancer prevention information and promotion of the HPV vaccine on university campuses to increase student awareness. At the same time, streamlining the vaccination appointment process and improving the accessibility and affordability of vaccines through strategic purchasing or subsidy programs are effective strategies to reduce reluctance to use HPV vaccines. To this end, concerted efforts are imperative to reduce vaccine hesitancy among university students in Guangdong Province through comprehensive and accurate information dissemination, policy optimization, and community collaboration to promote public health and social well-being.

In summary, these recommendations highlight the broader implications of this study for public health policy and future research. By implementing evidence-based strategies and fostering collaborative efforts, stakeholders can effectively reduce vaccine hesitancy and promote public health and social well-being in the region and beyond.

Yuehong Wei is a Master’s supervisor and Associate Director at the Guangzhou Center for Disease Control and Prevention, where he serves as Chief Physician. His expertise encompasses the monitoring, prevention, and control of intestinal infectious diseases, zoonotic diseases (including those transmitted by vectors), and rodent-borne diseases such as hemorrhagic fever with renal syndrome, leptospirosis, and scrub typhus. In recent years, Dr. Wei has led five research projects, including grants from the Natural Science Foundation of Guangdong Province, the Guangzhou Science and Technology Commission, and the Guangzhou Health Commission. He has also contributed to projects funded by the National Natural Science Foundation of China and the Guangdong Provincial Department of Science and Technology. Additionally, Dr. Wei has published over 30 papers, including eight in SCI-indexed journals.

Disclosure statement

No potential conflict of interest was reported by the author(s).
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