Factors associated with HPV vaccine hesitancy among college students: A cross-sectional survey based on 3Cs and structural equation model in China

ABSTRACT

Despite the high effectiveness of HPV vaccines in preventing infection, vaccine hesitancy remains a concern, particularly in China. This study aimed to explore college students’ attitudes toward HPV vaccination and identify associated factors. Data was collected through a cross-sectional survey using self-administered questionnaires in four cities from May to June 2022. Chi-square tests and logistic regression analyses were conducted to identify factors. Additionally, an integrated structural equation model (SEM) based on the 3Cs (confidence, convenience, complacency) was developed to understand underlying factors contributing to hesitancy. The results from 2261 valid questionnaires were enlightening. A significant 89.47% (59.4% for females) considered HPV vaccination necessary, with 9.82% remaining neutral and only 0.71% deeming it unnecessary. Factors like higher education, being a medical student, residing in urban areas, having medical insurance, more extraordinary living expenses, a family history of tumors, and a solid understanding of HPV played a role in perceiving the vaccine as necessary. Among the 1438 female respondents, 84.36% had no hesitancy toward HPV vaccination, 13.53% expressed hesitancy, and 2.11% refused vaccination. Factors like age, understanding of HPV, medical staff recommendations, living expenses, and family history influenced hesitancy levels. SEM revealed that the 3Cs significantly affected vaccine hesitancy. Factors like price, booking process, vaccination times, trust in vaccines, medical staff recommendations, efficiency, and risk perception collectively influenced hesitancy. In conclusion, this study found high acceptance of HPV vaccination but acknowledged the complexity of hesitancy factors. It recommends medical staff disseminate scientific knowledge, offer recommendations, simplify booking procedures, and expand vaccination sites to address vaccine hesitancy effectively.

KEYWORDS:

• Vaccine hesitancy
• human papilloma virus
• 3C model
• structural equation model
• college students

Introduction

Human papilloma virus (HPV) infection represents a significant public health concern that seriously threatens human health, especially among females.¹ According to GLOBOCAN, China reported several new cervical cancer cases, surpassing 110,000 and approximately 59,000 deaths in 2020, contributing the second-largest to the global burden of cervical cancer.² Finding an effective and safe way to prevent the development of high-grade cervical cancer and reduce the risk of severe cases and deaths has become an urgent mission.

Prophylactic HPV vaccines (bi/Qadri/nonovalent) have been demonstrated to be remarkably effective and safe in preventing the development of high-grade cervical cancer and reducing the risk of severe cases and deaths worldwide.³ Vaccination is considered one of the most effective ways to prevent related diseases.⁴ Many studies have confirmed that HPV vaccination is cost-effective in several countries.^5–7 The incidence and costs of cervical cancer are significantly decreasing in some countries, such as Australasia and Oceania, due to the widespread implementation of HPV vaccination.⁸ In, China，there are currently four HPV vaccines available : E-coli bv-HPV (Wantai, China, around 46 USD), bv-HPV (around 84 USD), qv-HPV (GSK, UK, around 112 USD), and 9 v-HPV (MSD, USA, around 182 USD). The accessibility of HPV vaccination to the general public is made possible through the convenience of online appointment scheduling.⁹ Notably, this preventative measure does not necessitate significant lifestyle changes.^10,11

Nevertheless, the emergence of vaccine hesitancy (VH) has hindered the smooth progress of public vaccination. VH could be defined as “Reluctance to accept or reject vaccination when available. ”,¹² which suggests that individuals’ reflection and deliberation about specific vaccines is not directly related to vaccine uptake.¹³ VH was considered one of the top ten issues threatening global health according to the WHO in 2019.¹⁴ HPV vaccination rate-decreasing events due to HPV VH have been reported in many countries and regions. For example, VH spread widely in Japan because adverse events were extensively covered in the media (although the events confirmed later that there was no relevance to HPV vaccination).¹⁵ Another study pointed out that VH may be the fundamental determinant of the low HPV vaccination rate in America.¹⁶ Evidence concerning Chinese HPV VH is still lacking, although some studies about HPV VH have been released in China, especially for college students.^17,18

College students belong to an essential population for HPV vaccination,¹⁹ and any reasons for VH could indicate broader problems.²⁰ The WHO considers that VH is influenced by the “3C” factors of complacency, convenience, and confidence.²¹ Researchers have widely adopted the 3C model to investigate the influencing factors of VH in other countries.^22,23 However, the 3C model was less frequently used in previous studies in China on college students’ VH to vaccinate against HPV. The research is often conducted in a few provinces/cities with small sample sizes using 3C theory on influenza vaccination^24,25 or only focused on medical students.²⁶ Other research just described the selection results for “3C”^27,28 or multivariate analyses.²⁹ No research has applied the 3C model to HPV vaccination hesitancy in college student groups, especially when combined with the structural equation model (SEM). SEM is an excellent analytical method to measure the influence of latent variables³⁰ to which 3Cs belong. Therefore, we used SEM combined with the 3Cs model to explore the factors related to HPV VH among college students and assessed the associated factors.

Study design and methods

Study design

The process of exploration design

The study is divided into two main parts. The first part examines the awareness of the importance of vaccination among male/female university students and identifies potential significant influencing factors. The second part discusses the influencing factors of vaccine hesitancy among female university students who were interviewed. In addition, we further investigate the potential variables and effects of significant factors related to vaccine hesitancy, utilizing a constructed structural equation modeling (SEM) for in-depth exploration (Figure 1).

Figure 1. The process of HPV vaccine hesitancy exploration.

Questionnaire design and data collection

The questionnaire was designed to gather information about students’ attitudes and perceptions regarding HPV, HPV vaccination, and sociodemographic characteristics. It was devised through a collaborative process involving epidemiologists and healthcare providers in the field of HPV, utilizing the previous literature and extensive discussions to ensure validity and effectiveness.

The questionnaire was ultimately divided into four parts. The first part introduced the study’s purpose and objectives, asked for voluntary participation, and assured anonymity. The second part collected participants’ sociodemographic information, such as sex, age, grade, type of registered residence, specialized subject, monthly living expenses, and medical insurance status.

The third part surveyed participants’ cognition about HPV, HPV VH, and their reasons. Some questions adopt different wording according to different sexes for better matching, although they express the same meaning (Table 1, for instance). The reasons for VH were classified into three dimensions: complacency, convenience, and confidence, based on the WHO VH 3Cs model. The analysis of VH according to the 3C model has been widely accepted worldwide, especially in COVID-19^31,32 and influenza^21,33 VH. Each dimension consists of several questions. Following this classification, 13 possible reasons were listed for participants to choose from, and open items were included for participants to add additional reasons. The following questions were based on the 3C theory in other studies^21,31,34,35 with a specific theoretical basis and practicability (Table 1).

Table 1. 3Cs factors of questions for HPV vaccine hesitancy.

Factors	Detailed questions
Confidence	Have you ever heard of adverse event reports of HPV vaccine (Safety)
	Trust level of the domestic HPV vaccine. (1 = Total distrust; 5 = Total trust)
	Trust level of HPV vaccine abroad. (1 = Total distrust; 5 = Total trust)
	Do you think HPV vaccine can prevent disease? (Effectiveness)
	Trust level of medical staff’s recommendation for HPV vaccine. (1 = Total distrust, 5 = Total trust)
Complacency	Risk Perception	Cervical cancer hazard degree. (0 = Extremely harmful; 10 = No harm)
		Possibility of cervical cancer. (0 = Very likely; 10 = Completely impossible)
		Fear of cervical cancer. (0 = Extreme fear; 10 = Fearless)
Convenience	The vaccine is at one’s own expense or too expensive. (Price)
	I do not know where to vaccinate.
	Don’t know where to obtain reliable vaccine information.
	The booking process is too cumbersome.
	I need to be vaccinated many times. It is too troublesome.

The fourth section encompassed an inquiry into the provenance of HPV vaccines, offering supplementary elucidation and further interrogations about the investigative content presented in the preceding third section. Some questions are only sex-specific (such as whether your family, classmates, or friends had recommended the HPV vaccine to you). These questions only showed female respondents because almost nobody will recommend the HPV vaccine for males in China. This may be partly because Chinese male college students are shy about discussing sex.³⁶

Sampling methods

This study used a multistage stratified sampling method. The first stratification stage was based on geographical location, economic development level, population, etc. Four cities were selected after carefully considering the aforementioned influencing factors (Shanghai, Guangzhou, Wuhan, and Nanning). In the second stage of stratification, we chose several schools in each city according to the type of school belonging to “Project 985,” “Project 211” (“Project 985” can be considered as the pinnacle of China’s higher education system, representing the highest level of excellence. “Project 211,” on the other hand, can be seen as the upper-middle tier of China’s higher education system.), and ordinary undergraduate or junior college.

Sample selection

The initial sample size was calculated by the following formula based on an error of 0.05 and a maximum permissible error$\mathit{\delta }$:

(1) $\mathit{n}=\frac{{\mathit{Z}}_{1-\mathit{\alpha }/2}^2\times \mathit{p}\left(1-\mathit{p}\right)}{{\delta }^2},\mathit{\delta }=0.1\mathit{p}$(1)

n represents the sample size required for the survey, and p is the survey’s expected prevalence or positive rate. The proportion of vaccine acceptance is estimated by referring to the latest published or authoritative survey data on vaccination willingness.

In this study, the acceptance rate of the HPV vaccine was based on the research results of Dai. Z³⁷ et al., found that 32.1% of female college students in China in 2022 expressed no hesitancy to receive the HPV vaccine. We estimated a minimum sample size of 170 female students and enlarged that to approximately 550 students (225 males and 225 females) in each city.

Statistical analysis

Chi-square tests were used to compare categorical variables, while a one-way analysis of variance was used to analyze continuous variables. Logistic regressions were used to investigate the factors associated with HPV VH (“accept” as the reference group; “hesitate” and “refuse” as the comparison groups). All analyses were performed using SPSS 26.0.

Among the female college students who chose “hesitating” and “refusing” to vaccinate, we used SEM combined with 3Cs to examine the factors associated with VH. All latent variables were incorporated into the SEM and estimated by IBM SPSS Amos 26.0 software. We used a maximum likelihood estimation to estimate the parameters’ coefficients and test each path’s significance to obtain the least-biased parameter estimates. We included direct paths from the latent variables of complacency, convenience, and confidence to VH to assess our assumptions. We also studied the indirect effect of the latent variable of convenience simultaneously. Standard estimation [(Xi-Xmean)/SD] was used to calculate the intensity of the direct and indirect effects,³⁸ which indicated the expected amount of change in engaging in VH or the mediator produced by a one-unit change in the corresponding latent variable. A p value < .05 was considered statistically significant throughout the study for all the statistical tests.

Study implementation and quality maintenance

Before the survey, participants were informed of their voluntary participation in the research and that they could terminate their involvement at any time during the questionnaire (this information will be presented prominently on the screen before the initiation of the first question). The questionnaire takes 3–10 min to complete, and each respondent could receive approximately 1.5 CNY as remuneration through random e-red envelopes in WeChat. The study was open to people of any sex.

To maintain survey quality, we implemented the following measures:

• Respondents had to complete the current question before proceeding to the next to ensure responses were received.

• If a respondent selected the same option for all questions, they were prompted to repeat their answers, and the survey result would only be recorded once they compiled.

• Questionnaires that took less than 3 minutes to complete were automatically marked invalid, and the respondent would not receive remuneration.

• The system would prompt him/her to restart if the respondent was willing.

A questionnaire that fulfills the aforementioned conditions was referred to as a “valid questionnaire.”

Ethics approval and consent to participate

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board, School of Public Health, Fudan University (IRB#2022-08-0992). Respondents were informed that they were free to withdraw from the study and that all data would be strictly confidential and used only for scientific analysis.

Results

From May to June 2022, a national survey on HPV VH was conducted among students from 66 colleges and universities across four cities.

Demographic characteristics

A total of 2261 valid questionnaires were collected in this study. Among them, 36.40% were males, and 63.60% were females. 66.30% of the respondents were undergraduates and below. 23.62% of respondents had been vaccinated at their own expense in the past five years. Among individuals under 20, 22.18% had received vaccines at their own expense. For those aged 20–26, the percentage was 23.88%, while for those above 26, it was 30.36%. Table 2 shows the participants’ characteristics.

Table 2. Participant characteristics and attitudes toward HPV vaccination necessity.

Factors		Total, N (%)	HPV vaccination necessity, N (%)			p Value
			Necessary	Neutral	Unnecessary
		2261	2023 (89.47)	222 (9.82)	16 (0.71)
Sex	Male	823 (36.40)	703 (85.42)	109 (13.24)	11 (1.34)	<.001
	Female	1438 (63.60)	1320 (91.79)	113 (7.86)	5 (0.35)
Age (years)	<20	559 (24.72)	500 (89.45)	57 (10.20)	2 (0.36)	.520
	20–26	1646 (72.80)	1470 (89.31)	162 (9.84)	14 (0.85)
	>26	56 (2.48)	53 (94.64)	3 (5.36)	0 (0.00)
City	Shanghai	687 (30.38)	586 (85.30)	94 (13.68)	7 (1.02)	<.001
	Wuhan	548 (24.24)	507 (92.52)	38 (6.93)	3 (0.55)
	Guangzhou	488 (21.58)	460 (94.26)	25 (5.12)	3 (0.61)
	Nanning	538 (23.80)	470 (87.36)	65 (12.08)	3 (0.56)
Education level	Junior college	452 (20.00)	371 (82.10)	74 (16.40)	7 (1.50)	<.001
	Undergraduate	1499 (66.30)	1362 (90.90)	131 (8.70)	6 (0.40)
	Postgraduate	310 (13.70)	290 (93.50)	17 (5.50)	3 (1.00)
Major	Science and technology or agriculture	368 (16.28)	313 (85.05)	50 (13.59)	5 (1.36)	<.001
	Social sciences	932 (41.22)	818 (87.77)	106 (11.37)	8 (0.86)
	Medicine	961 (42.50)	892 (92.82)	66 (6.87)	3 (0.31)
Living residence	Rural	1214 (53.69)	1067 (87.89)	136 (11.20)	11 (0.91)	.026
	Urban	1047 (46.31)	956 (91.31)	86 (8.21)	5 (0.48)
Medical insurance	Yes	2102 (92.97)	1892 (90.01)	196 (9.32)	14 (0.67)	.011
	No	159 (7.03)	131 (82.39)	26 (16.35)	2 (1.26)
Living expense (CNY)	<1000	294 (13.00)	247 (84.01)	45 (15.31)	2 (0.68)	.028
	1001–2000	1440 (63.69)	1303 (90.49)	128 (8.89)	9 (0.63)
	2001–3000	429 (18.97)	386 (89.98)	40 (9.32)	3 (0.70)
	>3000	98 (4.33)	87 (88.78)	9 (9.18)	2 (2.04)
Family history of tumor	Yes	196 (8.67)	185 (94.39)	8 (4.08)	3 (1.53)	.007
	No	2065 (91.33)	1838 (89.01)	214 (10.36)	13 (0.63)
Vaccinated at own expense in the past 5 years	Yes	534 (23.62)	497 (93.07)	36 (6.74)	1 (0.19)	.005
	No	1727 (76.38)	1526 (88.36)	186 (10.77)	15 (0.87)
HPV understanding level	Low	516 (22.82)	420 (81.40)	88 (17.05)	8 (1.55)	<.001
	Average	996 (44.05)	923 (92.67)	68 (6.83)	5 (0.50)
	High	749 (33.13)	680 (90.79)	66 (8.81)	3 (0.40)

HPV understanding levels are used to assess a person’s comprehension of HPV according to 5 true or false questions related to HPV. Higher scores indicate a better understanding of HPV.

“Vaccinated at own expense in the past 5 years” means any other vaccines except HPV vaccine.

HPV vaccination necessity

Among the respondents, 89.47% thought the HPV vaccination was necessary, 9.82% remained neutral, and 0.71% chose it unnecessary. Univariate analysis was employed to assess the necessity of HPV vaccination. Sociodemographic characteristics were significantly related to different levels of vaccination necessity (p < .05), such as sex, educational level, living expenses, major, having insurance and family tumor history (HPV-related cancers) or not, different levels of HPV understanding, place of residence, having been vaccinated at one’s own expense in the past 5 years, and province except age (p = .829) (Table 2).

Factors associated with VH

798 (84.36%) had no hesitancy for HPV vaccination. Approximately 128 (13.53%) people maintained “Hesitancy,” and 20 (2.11%) female college students refused HPV vaccination. Univariate analysis was also employed to assess the VH. Table 3 illustrates that age, living expenses, different levels of HPV understanding, having the HPV vaccine recommended by medical staff, and familial history of tumor are associated with VH (p < .05).

Table 3. Characteristics of female college students and their opinions for HPV vaccination.

Factors		Total, N (%)	HPV vaccination opinions, N (%)			p Value
			No hesitancy	Hesitancy	Refusal
		946	798 (84.36)	128 (13.53)	20 (2.11)
Age (years)	<20	253 (26.74)	220 (86.96)	29 (11.46)	4 (1.58)	.039
	20–26	675 (71.35)	566 (83.85)	95 (14.07)	14 (2.07)
	>26	18 (1.90)	12 (66.67)	4 (22.22)	2 (11.11)
City	Shanghai	278 (29.39)	230 (82.73)	43 (15.47)	5 (1.80)	.645
	Wuhan	232 (24.52)	201 (86.64)	25 (10.78)	6 (2.59)
	Guangzhou	186 (19.66)	158 (84.95)	26 (13.98)	2 (1.08)
	Nanning	250 (26.43)	209 (83.60)	34 (13.60)	7 (2.80)
Education level	Junior college	199 (21.04)	169 (84.92)	28 (14.07)	2 (1.01)	.058
	Undergraduate	666 (70.40)	560 (84.08)	93 (13.96)	13 (1.95)
	Postgraduate	81 (8.56)	69 (85.19)	7 (8.64)	5 (6.17)
Major	Science and technology or agriculture	94 (9.94)	81 (86.17)	11 (11.70)	2 (2.13)	.891
	Social sciences	412 (43.55)	342 (83.01)	61 (14.81)	9 (2.18)
	Medicine	440 (46.51)	375 (85.23)	56 (12.73)	9 (2.05)
Living residence	Rural	573 (60.57)	487 (84.99)	74 (12.91)	12 (2.09)	.787
	Urban	373 (39.43)	311 (83.38)	54 (14.48)	8 (2.14)
Medical insurance	Yes	880 (93.02)	741 (84.20)	120 (13.64)	19 (2.16)	.879
	No	66 (6.98)	57 (86.36)	8 (12.12)	1 (1.52)
Living expense (CNY)	<1000	133 (14.06)	106 (79.70)	22 (16.54)	5 (3.76)	.019
	1001–2000	648 (68.50)	560 (86.42)	78 (12.04)	10 (1.54)
	2001–3000	142 (15.01)	112 (78.87)	27 (19.01)	3 (2.11)
	>3000	23 (2.43)	20 (86.96)	1 (4.35)	2 (8.70)
Family history of tumor	Yes	74 (7.82)	63 (85.14)	4 (5.41)	7 (9.46)	<.001
	No	872 (92.20)	735 (84.30)	124 (14.20)	13 (1.50)
Vaccinated at own expense in the past 5 years	Yes	141 (14.90)	118 (83.69)	20 (14.18)	3 (2.13)	.970
	No	805 (85.10)	680 (84.47)	108 (13.42)	17 (2.11)
HPV vaccine recommended by medical staff	Yes	141 (14.90)	118 (83.69)	20 (14.18)	3 (2.13)	.040
	No	805 (85.10)	680 (84.47)	108 (13.42)	17 (2.11)
HPV understanding level	Low	189 (19.98)	154 (81.48)	25 (13.23)	10 (5.29)	.004
	Average	445 (47.04)	388 (87.19)	52 (11.69)	5 (1.12)
	High	312 (32.98)	256 (82.05)	51 (16.35)	5 (1.60)

Multivariable logistic regression analysis examined the significant factors identified in the aforementioned univariate analysis. The possibility of HPV VH was lower if college female students had a higher understanding of HPV (odds ratio [OR] = 0.44, 95% confidence interval [CI]: 0.24–0.83), younger ages (<20 years: OR = 0.20, CI: 0.06–0.82, 20–26 years: OR = 0.25, CI: 0.65–0.98), received the HPV vaccine recommended by medical staff (OR = 0.64, CI: 0.41–0.64), had less living expenses (OR = 0.16, CI: 0.03–0.81) and had a familial history of tumors (OR = 0.06, CI: 0.01–0.93). Meanwhile, female college students with a familial history of tumors (OR = 7.85, CI: 2.87–21.43) were more likely to refuse to be vaccinated. The results of the “familial history of tumor” suggest that once a female college student has a familial history of tumor, she will hold a firm attitude (accept or refuse although they are opposite) without hesitation (Table 4).

Table 4. Multivariate logistic regression to identify factors associated with HPV VH.

Factors		HPV vaccination opinions
		Hesitancy vs. No hesitancy			Refusal vs. No hesitancy
		OR	p Value	95% CI	OR	p Value	95% CI
Age (years)	(Ref >26)
	<20	0.20	.025	0.06–0.82	0.39	.403	0.04–3.49
	20–26	0.25	.047	0.65–0.98	0.41	.343	0.06–2.63
Living expense (CNY)	(Ref: >3000)
	<1000	4.05	.184	0.51–31.89	0.40	.316	0.07–2.39
	1001–2000	2.76	.326	0.36–20.92	0.16	.027	0.03–0.81
	2001–3000	4.73	.138	0.61–36.95	0.22	.122	0.03–1.49
Family history of tumor	(Ref: No)
	Yes	0.06	.044	0.01–0.93	7.85	<.001	2.87–21.43
HPV vaccine recommended by medical staff	(Ref: No)
	Yes	0.64	.048	0.41–0.64	0.40	.158	0.11–1.43
Level of HPV understanding	(Ref: Low)
	Average	0.44	.011	0.24–0.83	0.69	.713	0.09–5.41
	High	0.79	.331	0.50–1.26	3.96	.075	0.87–18.02

OR: odds ratio. CI: confidence interval. Boldface indicates statistical significance.

3C Model factors for VH combined with SEM analysis

To further explore the specific factors behind vaccination hesitancy among groups who chose “hesitancy” or “refusal” for HPV vaccination, a structural equation model was employed to analyze the latent factors building upon the 3C theory.

SEM assumed the effect of 3C factors as three latent variables on HPV VH combined with other social factors. After fineness optimization and further modifications, the final integrated model for HPV VH was established (Figure 2).

Figure 2. The final integrated SEM with sociodemographic and 3Cs effects on HPV VH.

Only results that have significant effects are presented. N = 148.

Each pathway was statistically significant using standardized estimates based on the best final integrated model (Figure 2). The confidence (standardized estimate coefficient [SE]: −0.242), convenience (SE: 0.143), and complacency (SE:0.371) factors all significantly and directly affected VH. No indirect effect was significant. Educational level (SE: 0.699, p < .001), age (SE: 0.602, p < .001), and family tumor history (SE: −0.282, p = .012) also contributed significantly to HPV VH. Meanwhile, the pathways of “Safety” (SE: 0.147) and “I do not know where to vaccinate.” (SE: 0.071), and “I do not know where to obtain reliable vaccine information.” (SE: 0.145) were not significant.

The goodness-of-fit indices of the integrated model for HPV vaccination hesitancy are displayed in Table 5. All fit indices fall within an acceptable range, signifying that the integrated model fits the data.³⁹

Table 5. Fit indices of the integrated model for HPV vaccine hesitancy.

Fit Indices	Acceptable Range	Measured Value
Degrees of freedom (df)	−	59
Chi-square (χ^2)	−	100.329
probability level (p)	>0.05	0.06
χ^2/df	<3.00	1.700
GFI	≥0.90	0.903
AGFI	≥0.90	0.913
CFI	>0.90	0.931
RMSEA	≤0.05	0.069
SRMR	<0.08	0.073

Discussion

Our research focused on college students and investigated their attitudes toward the significance of HPV vaccination. Moreover, we attempted to identify factors associated with VH among female college students using 3Cs and SEM across various provinces.

Vaccination necessity

Most of the students believed that HPV vaccination was imperative. A higher proportion of individuals considered it than other populations.⁴⁰ This finding suggests that college students may have a more significant concern regarding the potential harm of HPV. As age increases, the proportion of women who have received vaccines at their own expense gradually increases. This may be related to an improvement in their economic status. Our study also discovered that individuals with varying sexes, educational levels, living expenses, majors, insurance status, family tumor history, levels of HPV understanding, place of residence, and province exhibited various levels of necessity toward HPV vaccination.

Postgraduates, medical majors, urban residents, medical insurance, more living expenses, a family history of cancer, and a higher understanding of HPV may have a higher necessity for HPV vaccination. Some results are consistent with the findings of other researchers.^37,41,42

Vaccine hesitancy

This survey revealed a low degree of HPV VH among those who had not received or reserved the HPV vaccine, with less than 20% expressing hesitancy toward the vaccine. These findings indicated a lower level of hesitancy compared to other populations⁴⁰ and previous studies,^37,41 which suggests that an increasing number of females are willing to accept and approve of the beneficial effect of the HPV vaccine. This phenomenon may be credited to China’s accelerated approval of HPV vaccines and government, non-governmental organizations, manufacturers, and media efforts to strengthen health education and enhance HPV vaccination coverage.⁴³

Multivariate logistic regression showed that age, living expenses, different levels of HPV understanding, having an HPV vaccine recommended by medical personnel or not, and familial history of tumor were protective factors that people were more likely willing to vaccinate. “HPV understanding score” peaked at less VH with increasing scores and then began to hesitate or refuse with higher scores. It is worth noting that although persons were convinced of the necessity of HPV vaccination, they remained unsure regarding the urgency. That is why the factors associated with VH differ significantly from vaccination necessity, and other studies have reached a similar conclusion.⁴⁴

SEM with 3Cs factors

The SEM results illustrated the significant direct effects of 3Cs on HPV VH.

The confidence dimension had a significantly negative impact on VH. VH would be reduced by 0.242 standard deviations when one standard deviation is improved in confidence. Confidence is funneled toward the effectiveness of vaccines and the degree of trust in medical staff’s recommendation of HPV vaccines, especially in association with the degree of trust in HPV vaccines (domestic SE: 0.824 and foreign SE: 0.864). Previous studies reported that confidence was one of the most relevant factors for VH,⁴⁴ and trust and efficacy were the two most important factors for college students to decide whether to be vaccinated.⁴⁵ However, the indirect effects of hearing about HPV vaccine-related adverse events were not found to be significant toward VH in this study. This could be due to two reasons. First, there have been significantly fewer reports of HPV-negative events⁴⁶ in China in recent years. Second, individuals with higher education levels are generally less susceptible to believing in conspiracy theories. Chinese college students, in particular, are often perceived as a social group with a higher educational background than the national average.⁴⁷

Convenience was another critical factor in the respondents’ hesitancy about the HPV vaccine. An improvement of one standard deviation in convenience leads to a reduction of 0.143 standard deviations in VH. The change in convenience primarily reflects the necessity to receive multiple vaccinations and the price and ease of the booking process (SE: 0.753). This result is consistent with previous studies,^28,47 which indicate that obstacles to vaccination include price, complicated ordering processes, and too many injections. This may be because, in most parts of China, HPV vaccines are still paid out-of-pocket, and there are precise requirements for the timing and dosage of HPV vaccination, leading to an increase in the overall cost and inconvenience of vaccination.²⁸ Therefore, integrating HPV vaccination into the National Immunization Program or reducing the price of HPV vaccines could likely increase vaccination coverage. Additionally, making HPV vaccination accessible by providing flexible locations and periods that meet the needs of college students may also contribute to rising vaccination rates. Furthermore, simplifying the ordering process by using mobile vaccination vehicles to offer vaccination services or vaccination services in schools or pharmacies,⁴¹ with proper vaccine storage and circulation standards, could help streamline the process for individuals seeking vaccination.

Complacency was another important factor in the respondents’ hesitancy about the HPV vaccine. VH will be facilitated by 0.371 standard deviations when complacency improves by one standard deviation. Complacency was measured by risk perception of HPV, including the hazard degree of HPV, the possibility of suffering from HPV, and the fear degree of HPV, significantly affected by fear (SE up to 0.989). Consistent with previous studies,^17,28,41 this result indicated that students who thought cervical cancer was not harmful, impossible to get, and fearless were more likely to refuse vaccination. Excessive complacency can hinder the progress of HPV vaccination. A reasonable awareness of the harm of HPV can promote the vaccination of the HPV vaccine to a certain extent, so it is necessary to popularize HPV harm to the masses and the advantages of HPV vaccination.⁴⁸ The Internet plays a vital role in HPV vaccination propaganda. Using the Internet as a critical carrier of information dissemination may increase respondents’ understanding of HPV and HPV vaccines.⁴⁹

Limitations

The advantage of this study is that it used the multistage stratified sampling method and drew samples of different economic development levels from 4 cities. The sample size of the study, comprising a total of 2261 participants (N = 2261), was deemed adequate, demonstrating a satisfactory level of representativeness. This comprehensive sampling approach enhances the generalizability of the findings and provides a valuable reference for future investigations into COVID-19 VH. However, this study still has a few limitations.

According to previous studies of other people, political party identity,⁵⁰ having a partner or not^28,51 (including opposite-sex and same-sex couples), and sexual orientation⁵¹ may also be significant factors for VH, which are not included in our study because they are sensitive topics in China. It is challenging to collect real answers. The other is that the sample size of SEM is manageable (N = 148), although the result of the final integrated SEM can also be accepted. A larger sample size may have better-fitting results and more accurate results.

Conclusions

Compared to the past, there has been an improvement in the perceived necessity of vaccination, and VH among Chinese college students has decreased somewhat. The 3Cs model factors related to VH could be summarized as “more confidence and convenience and less complacency leading to reduced hesitancy.” Sociodemographic characteristics, such as age, educational level, and living expenses, were also statistically relevant. To further improve VH, medical staff should spread relevant scientific knowledge and give recommendations to focus populations. Simultaneously simplifying the booking process, such as using mobile vaccination vehicles and increasing the appropriate number of vaccination sites, such as schools or COVID-19 testing points, are also crucial to reducing VH. Additionally, facing COVID-19 challenges today, combining 3C factors with sociodemographics in SEM on HPV vaccination can provide helpful information to analyze COVID-19 VH and develop COVID-19 vaccination strategies.

Authors’ contributions

Conceptualization, L.Z., Y.H., C.C., P.L. and T.C.; methodology, L.Z. and T.C; software, C.C.; validation, L.Z. and T.C.; formal analysis, C.C., Y.H. and L.Z.; investigation, L.Z., Y.H., T.C., and C.C.; resources, L.Z.; data curation, L.Z. and C.C.; writing-original draft preparation, C.C. and L.Z; writing-review and editing, L.Z., M.H., T.C. and C.C.; visualization, L.Z., P.L.; supervision, T.C. and L.Z.; project administration, L.Z and P.L. All authors have read and agreed to the published version of the manuscript.

Ethics approval and consent to participate

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board, School of Public Health, Fudan University (IRB#2022-08-0992).

Disclosure statement

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

Data availability statement

Contact the corresponding author to obtain relevant data and information such as survey questionnaires.

Additional information

Funding

This research was funded by “The 14th Five Year Plan” Hubei Provincial advantaged and characteristic disciplines (groups) project of Wuhan University of Science and Technology [grant number C0202].