HPV vaccine intention among university students during suspension of active recommendation in Japan

ABSTRACT

In Japan, active recommendation of the human papillomavirus vaccine was withheld between 2013 and 2021 due to adverse reaction reports. This resulted in low vaccine coverage with reports from less than 1%. This study aimed to investigate if knowledge and health-belief related factors associated with vaccine intention among young adolescents with the hope that our findings may be helpful in promotion campaigns. We recruited students in four colleges and universities in Akita Prefecture from 2020 to 2021 who had never been vaccinated. A total of 318 students (male 54%, mean age 21 years) responded to a self-administered questionnaire; only 6% reported immediate vaccine intention, and 61% reported no such intention or “do not know.” The correct percentages of 20-item knowledge about HPV vaccine-related morbidity, mortality, and prevention were very low regardless of gender (average males 41.4% vs. females 39.6%). Multivariable logistic regression models demonstrated that in males, higher levels of literacy, perceived susceptibility, and place for vaccination (logistical barrier) were associated with HPV vaccine intention, whereas “no need now” was associated with less intention. In females, a higher level of knowledge was significantly associated with vaccine intention, whereas “concerns of adverse effects” were associated with less intention.

KEYWORDS:

• Vaccine intention
• Japan
• HPV vaccines
• vaccine acceptability
• university students
• active recommendation

Introduction

Cervical cancer is the second most common cancer in females worldwide and is mostly caused by human papillomavirus (HPV) infection of the cervix; more than 80% of HPV-related cancers involve the cervix, and the scientific evidence on vaccines as the primary prevention is being accumulated to reduce cervical cancer risk at the population level.^1–4 Many countries in Europe and the United States launched routine HPV vaccination programs for girls aged 9 to 13 between 2006 and 2012. Vaccine completion rates among eligible females were reported to be 80% in Australia,⁵ 87% in the United Kingdom,^6,7 50% in the United States,^8,9 and 85% in Scandinavia,^10,11 which were among the first to adopt HPV vaccination as a publicly funded national program, the infection rate of the targeted HPV (types 16 and 18) has already decreased dramatically in the vaccinated generation.¹ In Japan, the bivalent HPV vaccine (2vHPV, Cervarix, GlaxoSmithKline, Rixensart, Belgium) was first approved for production and marketing in 2010, and in April 2013, the HPV vaccine was officially included in routine vaccination under the Immunization Law. However, due to numerous case reports of various somatic symptoms such as chronic pain and movement disorders after vaccination,¹² the active recommendation for vaccination was officially stopped just two months after its introduction. Under Article 8 of the National Immunization Law, the target population (i.e., girls aged 12–16 years) was provided free HPV vaccines. According to a study¹² in Sapparo, Japan, prior to the suspension of recommendations (2013), rates of HPV vaccination ranged from 73.6–77.2% at initiation and 68.4–74.0% for three dose completion in girls in the 1994–98 birth cohorts, but completion rates plummeted to only 0.6% after suspension.¹² Nine years later, in November 2021, the Japanese Ministry of Health, Labor and Welfare (MHLW) suddenly announced the resumption of active recommendations for the HPV vaccine. Although the ministry released catch-up vaccinations for girls born between 1997 and 2005 (i.e., girls aged 17–25 years in 2022) who missed the opportunity during the suspension, it may not be easy to bring the HPV uptake rate back to the level before the suspension. Furthermore, given that approximately 3,000 women lose their lives due to cervical cancer every year in Japan,¹³ and cervical cancer screening has been historically low in Japan,¹⁴ the vaccine is a primary preventive measure; thus, behavior modification is definitely important for not only females but also males considering its sexually transmitted features.¹⁵

The HPV infection in males has been linked to penile, anal, rectal, prostate, and oropharyngeal cancers.¹⁶ A meta-analysis¹⁷ of 42 articles including 4,250 men showed that the pooled prevalence of HPV DNA in oropharyngeal and penile cancers was 45% and 48%, respectively, which indicates that HPV associated with cancer is not rare in males and is more likely to incur a significant consequence on a male’s life. The countries where the HPV vaccine for males is recommended by the National Advisory Committee on Immunization are mainly the US and Australia.¹⁸ However, a study among healthy youth in the US showed that the vaccine first dose uptake is still very low: 3% among 6038 males aged between 18 and 21 years.¹⁹ Such low vaccine uptake in a country where males are publicly subsidized for immunization might suggest that it is highly improbable that Japanese males intended to get HPV shots even after the government approved the quadrivalent HPV vaccine (4vHPV, Gardasil, MSD, Lyon, France) in December 2020 for males aged nine years and older.

Previously, knowledge, health literacy, and health belief-related factors played a pivotal role to modify vaccine intention and uptake.^20,21 For example, according to the theory of health-belief model,²² perceived susceptibility, severity, and benefits, are promotors to induce favorable behaviors, while perceived barriers are the inhibitory factors. In this study, in the light of resuming active recommendation, we investigated if these health belief-related factors are associated with vaccine intention and, if so, which factor would be the more powerful promoter compared to the others for enhancing vaccine behavioral intentions so that we can exploit any relevant factors to be included in promotional campaigns. Therefore, this study aimed to identify the effects of knowledge, health literacy, and health belief-related factors (perceived susceptibility and severity, and barriers) on vaccine intention among college and university students, the majority of whom missed the opportunity for active recommendation. In this study, we also included male students because we believed males’ awareness of HPV infection may be a key factor to successful behavioral change of both genders.

Materials and methods

Study participants

In this cross-sectional study, we recruited all undergraduate and graduate college and university students who belonged to four universities in Akita Prefecture from July 2020 to January 2021. The inclusion criteria were 1) never been vaccinated against HPV, 2) be of Japanese ethnicity, 3) be either male or female, and 4) be aged between 18 and 35 years. Recruitment methods included electronic bulletin boards addressed to individual university students, classroom websites, and on-campus notice boards. The students accessed the Google Forms by scanning the QR code from the flyer and reading the purpose of the study. The study’s aim and survey procedures were provided on the website of Akita University Department of Public Health. A participant was given a 500 JPY (US 5$) equivalent gift card and was also informed that they can withdraw anytime using a form posted on the website. A student who agreed to participate in the study submitted a consent form to the research office. They were then approached directly by the research office through e-mails to answer a baseline questionnaire created on Google Forms via a link in the e-mail. There was a total of 398 survey respondents, both male and female. Of these, 22 females were vaccinated once, 23 females were vaccinated twice, and 35 females were vaccinated thrice. Thus, after excluding these 80 students, 318 students were included in the analyses. This study was approved by the Ethics Committee of Akita University (# 2387) and conducted according to the Declaration of Helsinki.

Questionnaire

The question items included the intention to receive HPV vaccine shots, knowledge, health literacy and health beliefs about the HPV vaccine and uterine cancer prevention, and the characteristics of participants. The characteristics included sex, age, university, faculty departments (medicine, nursing, science technology, or otherwise), smoking (current/ever/never) and drinking (everyday/a few times a week/seldom/never) habits, sleep duration, frequency of having breakfasts per week, and exercise volume and intensity based on a unit of metabolic equivalents (METs)—light (up to 4 METS), moderate (5–6 METS), vigorous (7–8 METS), and very vigorous (9–10 METS)—and multiplied with the exercise time period.

Intention to receive HPV vaccine shots

The outcome of this study is students’ intention to receive the HPV vaccine. We asked our study participants, “At what time do you intend to receive the HPV vaccine?” Their answers were based on a 5-point scale: “immediately” = 1, “within six months” = 2, “within a year” = 3, “within three years” = 4, and “no intention to receive a vaccine” or “not sure” = 5. As the study was performed under the coronavirus pandemic, there was a very small percentage who answered “immediately.” Subsequently, we combined the categories from “immediately” to “within 3 years” into one group and made a binary outcome compared to otherwise. We also asked about reasons for not yet being vaccinated, referring to previous literature: I don’t know where to get vaccinated (Place to receive the shot); My parents are opposed to vaccination (Parental opposition); I’m afraid of adverse reactions to vaccinations (Concerns about side effects); I don’t want to bother getting vaccinated (Feel troublesome); I am sexually inactive; Vaccinations are expensive for me (Expensive); I won’t get infected HPV; My friends are not vaccinated; Vaccination is not necessary if I will have a regular checkup (Checkup is enough); My school does not recommend vaccination; I am afraid of getting infected by COVID-19 (I do not want to go out for non-urgent and non-essential prevention of HPV infection); and others.

Knowledge

To measure the knowledge of HPV, the authors created 20 statements; the first ten included the following: 1. HPV is a human immunodeficiency virus; 2. There are four types of HPV; 3. HPV causes cancer of the uterine body; 4. HPV cannot be transmitted by a single sexual intercourse; 5. HPV can only be transmitted by males, not by females; 6. Types 6 and 11 cause more than two-thirds of all cervical cancer; 7. Cervical cancer can be prevented with vaccines; 8. Cervical cancer screening is done by cytology; 9. The age limit for HPV screening is 35 years old; 10. Cervical cancer is caused by persistent high-risk HPV infection. The response patterns of these first ten items were either “correct,” “incorrect,” or “do not know.” The next 10 question items were: 11. What do you think is the screening rate for cervical cancer in Japan? (1. 80% or more, 2. 60–80%, 3. 40–60%, 4. 20–40%, 5. 20% or less); 12. In some foreign countries, HPV vaccination is also given to males (1. correct, 2. don’t know, 3. incorrect); 13. What percentage of females with a history of sexually transmitted infections do you think will experience HPV infection by the time they are 50 years old? (1. 80% or more, 2. 60–80%, 3. 40–60%, 4. 20–40%, 5. 20% or less); 14. Which types of HPV are less likely to cause cancer? (1. type 16, 2. type 18, 3. type 52, 4. type 31, 5. type 2); 15. Which is the leading cause of cancer death among females in their 20s and 30s? (1. lung, 2. stomach, 3. liver, 4. uterus, 5. breast); 16. It is necessary to have a regular checkup for uterine cancer even if you have the HPV vaccine (1. correct, 2. don’t know, 3. incorrect); 17. How effective do you think the cervical cancer vaccination is in preventing cervical cancer? (1. 100%, 2. 80–90%, 3. 60–70%, 4. 50% or less); 18. How often do you think serious adverse reactions will occur due to vaccination compared to the flu vaccine? (1. Low, 2. About the same, 3. Somewhat high, 4. Extremely high); 19. What do you think is the probability of cervical cancer occurring in the lifetime of a female? (1. one per two persons, 2. one per 12 persons, 3. one in 75 persons, 4. one in 155 persons); 20. Which of the following do you think is used to confirm the diagnosis of cervical cancer? (1. cytology, 2. hemolysis, 3. HPV virus type, 4. colposcopy (histology), 5. Pap smear)

The percentage of correct answers was estimated for each participant and then divided into binary with the median of its distribution.

Health literacy

Referring to a previous study,²⁰ we investigated health literacy regarding the HPV vaccine based on the following five factors: (1) to be able to collect information related to the HPV vaccine and cervical cancer screening from various sources, such as newspapers, books, TV, and the Internet; (2) to be able to select the information one wants from among a large amount of information related to the HPV vaccine and cervical cancer screening; (3) to be able to consider the credibility of the information related to the HPV vaccine and cervical cancer screening; (4) to understand and communicate information related to the HPV vaccine and cervical cancer screening to others: (5) to decide on plans and actions to improve health based on information related to the HPV vaccine and cervical cancer screening. The questions were asked on a 6-point Likert scale, asking respondents to choose only one option from the following: 1. very easy, 2. somewhat easy, 3. intermediate, 4. somewhat difficult, 5. very difficult, and 6. don’t know/do not apply. Each item was recalculated by subtracting from “6,” ranging from 1, “strongly difficult,” to 5, “strongly easy” without counting on “don’t know/do not apply,” indicating a higher score is more likely to have higher literacy. The total score was divided into two groups at the median score.

Health beliefs

We utilized the health belief model to identify factors related to vaccine intention and constructed the following statements in relation to HPV vaccine and cervical cancer: (1) I regard myself as susceptible to HPV infection (perceived susceptibility); (2) Cervical cancer is a life-threatening disease (perceived severity); (3) I believe it would have potentially serious consequences if I get cervical cancer (perceived severity); (4) Vaccination would reduce the susceptibility or severity or lead to other positive outcomes (perceived benefit); (5) The vaccine is too expensive (perceived barriers); (6) I’m worried about the adverse effects of the vaccine (perceived barriers); (7) I’m too busy to go for the vaccination (perceived barriers); (8) I don’t know a place where I can get the shot (perceived barriers); (9) Three doses of vaccination is too much trouble (perceived barriers); (10) My parents don’t agree with the vaccination (perceived barriers); (11) I do not think I need it now (perceived no benefit). The respondents were asked to choose only one option from the following: 1. agree, 2. somewhat agree, 3. undecided, 4. do not really agree, 5. disagree, and 6. don’t know. The response patterns were further grouped into binary with “agree, somewhat agree” or “otherwise.”

Statistical analyses

The scores for knowledge and literacy, and the percentages of the health beliefs were compared between genders by using a t-test, an analysis of variance, or a chi-square test. The baseline characteristics, the reasons for non-vaccination, the correct numbers and percentages of the 20 knowledge questions, and the number of the participants who agreed/strongly agreed that they had the ability to understand each literacy item were compared between unvaccinated males and females using a chi-square test. In order to estimate the effect of each factor of knowledge, literacy, and health beliefs on vaccine intention, we calculated odds ratios along with 95% CIs using logistic regression analyses. Then, to further identify which factors would be mostly associated with the intention of receiving the HPV vaccine, we performed multivariate logistic regression analyses adjusting for faculty, age, smoking, drinking, sleeping, exercise, and breakfast. These adjustments were based on a previous study that found that an unhealthy lifestyle may be attributed to low adherence to HPV vaccination.²³ The purposeful selection process begins with a univariate analysis of each variable.²⁴ Any variable having a significant univariate test at some arbitrary level is selected as a candidate for the multivariate analysis. We base this on the Wald test from logistic regression and a p-value cutoff point of 0.05.^25,26 These logistic regression models were performed stratified by gender.

All statistical analysis was performed using Stata (version 17.0 SE – Standard Edition: Stata Corporation, Texas), with a significance level of 5% and two-tailed tests.

Results

Baseline characteristics in never vaccinated males and females

In a total of 318 students who had never been vaccinated, the gender ratio was 1.2:1.0 (173 males, 54%; 145 females, 46%), the mean age was 21 years, and the proportion of students in four universities was 61% in A, 18% in B, 19% in C, and 7% in D, 40% belonging to healthcare department. More than 90% of both genders were under 25 years of age. Males were more likely to have smoking (p = .008), drinking (p < .001), and exercise habits (p = .029) compared to females (supplementary Table S1).

The most frequent reason for non-vaccination in female students was “Concerns about side effects,” followed by “Parental opposition.” These were significantly higher in females than in males (p < .001). In contrast, the reasons more frequently observed in males than in females were “I won’t get infected HPV (p = .003)” and “Afraid of getting infected with COVID-19 (p = .043, supplementary Table S2).”

Knowledge, literacy, and health beliefs according to gender

The correct percentages of responses to 20 items were comparable between males and females (average, 41.4% vs. 39.6%, p = .323), and the details of each question are presented in supplementary table 3. For literacy, 53% of the total students exceeded the median literacy, and there was no gender difference for each of the five questions (supplementary Table S4). For health beliefs (Table 1), females were more likely to perceive susceptibility to HPV (p < .001) and have concerns about adverse effects (p < .001); but they reported that they did not have time for the shot (p = .001) and their parents opposed getting it (p < .001). By contrast, males were more likely to perceive the HPV vaccine as efficacious for cervical cancer prevention (p = .015, Table 1). For the question “At what time do you intend to receive the HPV vaccine?,” only 6% of males and females reported immediate vaccine intention, whereas 61% of both genders reported no intention or “do not know” (p = .683, Table 1).

Table 1. Knowledge, literacy, health beliefs scores according to gender.

		Total (n = 318, 100%)		Male (n = 173, 48%)		Female (n=145, 46%)		p
Variables		Mean	SD	Mean	SD	Mean	SD
Knowledge		40.6	0.2	41.4	0.2	39.6	0.1	.323
Literacy		10.5	5.7	10.3	5.9	9.8	8.9	.452
Health beliefs		n	%	N	%	n	%
Perceived susceptibility	Being susceptible	124	39	51	29	73	50	<.001
Perceived severity	Life-threatening	245	77	129	75	116	80	.251
Perceived severity	Serious consequences	258	81	142	82	116	80	.637
Benefit	Prevention	209	66	124	72	85	59	.015
No benefit	No need Now	89	28	46	27	43	30	.544
Barrier
	Expensive	209	66	108	62	101	70	.176
	Concerns about adverse effect	170	53	69	40	101	70	<.001
	Busy and don’t have time	121	38	51	29	70	48	.001
	Do not know where to get the shot	191	60	104	60	87	60	.983
	Feels troublesome	183	58	94	54	89	61	.206
	Parental opposition	57	18	13	8	44	30	<.001
At what time do you intend to receive the HPV vaccine?								.683
	Immediately*	18	5.7	12	7.02	6	4.14
	Within six months	14	4.43	8	4.68	6	4.14
	Within a year	29	9.18	16	9.36	13	8.97
	Within three years	61	19.3	29	16.96	32	22.07
	No intention or do not know	194	61.39	106	61.99	88	60.69

*Missing n = 2.

Intention to vaccinate and related factors of vaccination behavior in the unvaccinated male group (Table 2, Figure 1)

Among the 173 males who had not ever been vaccinated, 38% reported the intention to receive the HPV vaccine sometime between “immediately” and “within 3 years.” In the univariate logistic regression analyses, “Knowledge,” “Literacy,” “Perceived susceptibility,” “Don’t know where to get the shot,” and “No need now” for health-belief-related factors were significantly associated with the intention of receiving HPV vaccination at p < .2. Adjusting for these factors, the multivariable logistic regression models found that “Literacy (OR 2.12, 95% CI: 1.02–4.41),” “Perceived susceptibility (OR 2.46, 95% CI: 1.16–5.22),” “Do not know where to get (OR 2.23, 95% CI: 1.06–4.70)” were significantly associated with vaccine intention, sometime between “immediately” and “within 3 years.” whereas those who reported “No need now” were significantly associated with lesser intention (OR 0.33, 95% CI: 0.14–0.78).” Age, faculty, smoking and drinking habits, exercise, and breakfast routines were not significantly associated with vaccine intention in males.

Table 2. Factors associated with intention to vaccinate among unvaccinated males.

		“Immediately” to “within 3 years” N = 65, 38%	“No plan to vaccinate” N = 106, 62％	Logistic regression models for vaccine intention from “immediately” to “within 3 years”
				Univariable			Multivariable
Variables		N (%)	N (%)	OR	95%CI	P	OR	95%CI
Faculty	Healthcare	27 (42)	48 (45)	0.86	0.46–1.60	.204	-	-
Age	≧20	42 (65)	74 (70)	0.76	0.40–1.48	.426	-	-
Smoking	Now or ever	6 (9)	8 (8)	1.25	0.41–3.77	.697	-	-
Drinking	Frequently	23 (35)	50 (47)	0.61	0.33–1.16	.132	-	-
Sleeping	≧ 6h	56 (86)	98 (92)	0.51	0.19–1.39	.188	-	-
Exercise	≧Median	41 (63)	57 (54)	1.47	0.78–2.76	.233	-	-
Breakfast	Everyday	26 (40)	53 (50)	0.67	0.36–1.25	.204	-	-
Knowledge	≥ Median	45 (69)	54 (51)	2.17	1.13–1 4.15	.019	1.48	0.70–3.13
Literacy	≥ Median	44 (68)	50 (47)	2.35	1.23–4.47	.01	2.12	1.02–4.41
Health beliefs
Perceived susceptibility	Being susceptible	29 (45)	21 (20)	3.26	1.65–6.46	.001	2.46	1.16–5.22
Perceived severity	Life-threatening	52 (80)	76 (71)	1.58	0.75–3.31	.225	-	-
Perceived severity	Serious consequences	52 (80)	89 (84)	0.76	0.34–1.70	.509	-	-
Benefit	Prevention	48 (74)	75 (71)	1.18	0.58–2.34	.662	-	-
No benefit	No need Now	9 (14)	37 (35)	0.3	0.13–0.67	.003	0.33	0.14–0.78
Barrier
	Expensive	38 (58)	70 (66)	0.72	0.38–1.37	.319	-	-
	Concerns about adverse effect	27 (42)	42 (40)	1.08	0.58–2.03	.804	-	-
	Busy and don’t have time	21 (32)	29 (27)	1.27	0.65–2.48	.49	-	-
	Do not know where to get the shot	46 (71)	57 (54)	2.08	1.08–4.01	.028	2.23	1.06–4.70
	Feels troublesome	32 (49)	61 (58)	0.72	0.39–1.33	.289	-	-
	Parental opposition	6 (9)	7 (7)	1.44	0.46–4.48	.529	-	-

Intention to vaccinate and related factors of vaccination behavior in the unvaccinated female group (Table 3, Figure 1)

Among the 145 females who had not ever been vaccinated, 39% reported the intention to receive the HPV vaccine sometime between “immediately” and “within 3 years.” “Faculty,” “Knowledge,” “Prevention,” “Concerns about adverse effect,” and “Parent opposition” were significantly associated with an intention in univariate logistic regression models. After adjusting for these factors, multivariable models demonstrated that a higher level of “knowledge” was significantly associated with a higher intention to receive the HPV vaccine shot sometime between “immediately” and “within 3 years” (OR, 6.15, 95% CI: 2.54–14.88), whereas those who reported “concerns of adverse effects” were associated with lower vaccine intention (OR 0.36, 95% CI: 0.15–0.87). Age, faculty, smoking and drinking habits, exercise, and breakfast routines were not significantly associated with vaccine intention in females.

Figure 1. Forest plot of HPV vaccine intention of each factor among unvaccinated males and females.

Note: Significant positive factors associated with HPV vaccine intention were higher “literacy”, “being susceptible” and “do not know where to get the shot” among males and higher “knowledge” among females. Significant negative factors associated with HPV vaccine intention were “no need now” among males and “parental opposition” among females.

Table 3. Factors associated with intention to vaccinate among unvaccinated females.

		“Immediately” to “within 3 years” N = 57, 39%	“Not plan to vaccinate” N = 88, 61%	Logistic regression models for vaccine intention from “immediately” to “within 3 years”
				Univariable			Multivariable
Variables		N (%)	N (%)	OR	95%CI	P	OR	95%CI
Faculty	Healthcare	27 (47)	25 (28)	2.27	1.13–4.55	.021	1.31	0.57–3.03
Age	≥20	25 (44)	31 (36)	1.41	0.71–2.79	.323	-	-
Smoking	Now or ever	55 (96)	88 (100)	-	-	-	-	-
Drinking	Frequently	41 (72)	75 (85)	2.25	0.99–5.14	.054	-	-
Sleeping	≥6h	52 (93)	77 (89)	1.69	0.50–5.67	.397	-	-
Exercise	≥ Median	23 (40)	43 (49)	0.71	0.36–1.39	.315	-	-
Breakfast	Everyday	28 (49)	36 (41)	1.37	0.70–2.68	.361	-	-
Knowledge	≥ Median	44 (77)	29 (33)	6.89	3.21–14.80	<0.001	6.27	2.59–15.16
Literacy	≥ Median	32 (56)	41 (47)	1.47	0.75–2.87	.262	-	-
Health beliefs
Perceived susceptibility	Being susceptible	34 (60)	39 (44)	1.86	0.95, 3.65	.071	1.47	0.66–3.30
Perceived severity	Life-threatening	46 (81)	70 (80)	1.08	0.47–2.48	.865	-	-
Perceived severity	Serious consequences	47 (82)	69 (78)	1.29	0.53–3.03	.552	-	-
Benefit	Prevention	41 (72)	44 (50)	2.56	1.26–5.23	.009	1.25	0.53–2.93
No benefit	No need Now	13 (23)	30 (34)	0.57	0.27–1.22	.146	0.78	0.32–1.88
Barrier
	Expensive	39 (68)	62 (70)	0.91	0.44–1.87	.795	-	-
	Concerns about adverse effect	32 (56)	69 (78)	0.35	0.17–0.73	.945	0.34	0.14–0.83
	Busy and don’t have time	28 (49)	42 (48)	1.06	0.54–2.06	.87	-	-
	Do not know where to get the shot	34 (60)	53 (60)	0.98	0.50–1.93	.945	-	-
	Feels troublesome	36 (63)	53 (60)	1.13	0.60–2.25	.723	-	-
	Parental opposition	11 (19)	33 (38)	0.4	0.18–0.88	.02	0.46	0.18–1.14

Discussion

This cross-sectional study investigated HPV vaccine intention and its related factors among male and female students from four colleges and universities in Japan. We confirmed a very low level of HPV vaccine acceptability; only 6% of males and females reported immediate vaccine intention, whereas 61% reported no such intention or “do not know.” The present study results show that vaccine intention is much lower than those previously reported in other Asian countries.²⁷ We recruited students just after the end of the first nationwide state of emergency in June, 2020. Although Japan did not enforce a strict lockdown like other countries, university and college students were required to self-quarantine by their schools²⁸ and Akita University was closed until September of 2020. Previous studies reported their concerns about the decline in HPV uptake and cancer screening during the COVID-19 pandemic.^29,30 However, as shown in supplementary Table S2, only 3% of respondents reported that they did not vaccinate because of COVID-19 infection. Such low percentages may indicate that the majority of unvaccinated students might have been a consequence of the missed opportunity to receive the active recommendation and not of the COVID-19 pandemic. Active recommendation resumed at the end of 2021, but our result indicates that the low vaccine uptake currently reported in Japan will probably not recover unless strong countermeasures are taken. In our study, we found that in males, higher levels of literacy, perceived susceptibility, and place for vaccination (barrier) were associated with an increased HPV vaccine intention, whereas “no need now” was associated with less intention. In females, a higher level of “knowledge” was significantly associated with higher vaccine intention, whereas “concern about adverse effects” was associated with lower vaccine intention. These findings suggest that for males, HPV awareness campaigns, and for females, information to increase knowledge levels, including the safety and efficacy of the HPV vaccine, may help increase vaccine acceptability. We discuss our results referring to previous literature.

In this study, less than 50% of male and female had correct knowledge of 20 items about the morbidity, mortality, and prevention associated with HPV infection. Although a simple comparison with previous studies is difficult, the percentages of correct knowledge in our study were lower than the results previously reported, including a study among female college students (65%) ³¹ and studies of both genders (52%).^31,32 According to a study that investigated health belief models,²² “knowledge” is a fundamental factor and related to perceived susceptibility, severity, price, and concerns about adverse effects. In previous studies that investigated HPV vaccine behavior, a study among undergraduate students in Hong Kong³² underscored the importance of “knowledge” as a cue to vaccine behavior.

Our additional analyses showed a high correlation between a higher level of knowledge and other health beliefs, including perceived susceptibility and severity, prevention, and parental opposition. We also confirmed that knowledge was associated with vaccine intention in females but not in males. This finding was consistent with a previous study³³ that reported that informing male about the benefits of male HPV vaccination for reducing cervical cancer risk in females did not increase males’ interest in the vaccine. Instead, we found that the health belief factors were associated with HPV vaccine intention in males and those were “perceived susceptibility,” “do not know where to get the shot (barrier),” and “no need now (perceived no benefit).” Among these, it is quite interesting that “I don’t know where to get the shot” became a significant factor. This suggests that male students would be willing to be vaccinated if they knew where to receive vaccine shots. However, one careful interpretation should be mentioned here. There is another important logistical barrier other than “where to receive vaccine” which includes “cost,”³⁴ but it (i.e., “expensive” in our study) was not identified. This indicates that because males are not included in the HPV vaccine target under routine immunization package in Japan, they are less likely to be exposed to any detailed vaccine information (i.e., cost, place, adverse effects, efficacy, or the numbers of shots), and thus might not be able to even know the price of HPV vaccination. Similarly, perceived susceptibility and “no need (no benefit)” in males underscored the importance of perception of health matters, suggesting that males might not be ready to seriously view HPV infection as their own health issue yet.

According to a recent systematic review on HPV vaccine intention in females,³⁵ perceived susceptibility and severity, barriers, and adverse effects were the significant associated factors. In contrast, in our study, “concern about adverse effects” was the only significant factor. The difference between our study and those previous studies may be explained by a low level of knowledge of the HPV vaccine, morbidity, mortality, prevention, a long-time dispute over adverse effects, as well as the role of social media in releasing sensitive news of lawsuits by young girls who were bedridden and adversely affected by HPV vaccine.^36,37

The higher scores of health literacy in males were associated with the increased vaccine intention among males. A systematic review of 22 studies and 10,997 participants in nine countries reported that health literacy interventions could improve changes in health behavior.³⁸ In our study, however, health literacy was only associated with males, but not females. Insignificant effects among the females in our study may be explained by the difficulty in catching up with the rapidly changing and accurate information. For example, in Japan, active recommendations had been withheld by the government until very recently.^37,39 In contrast, many OECD countries actively promote HPV vaccination in uterine cancer prevention packages, referring to the WHO’s recommendation, even as the safety of the HPV vaccine is monitored.⁴⁰ Finally, in 2021, Japan resumed the active recommendation of HPV vaccination.⁴¹ However, neurological symptoms after the HPV vaccine are still controversial,^36,42,43 and thus, such domestic situations might have left young females confused. By contrast, significant effects of literacy in males might be explained by higher levels of confidence in males than in females, previously reported by a meta-analysis and several studies on self-esteem (proxy of self-confidence).^44–47 These reported that males score higher on standard measures of global self-esteem than females, although the difference is small.^44–47 Thus, the interpretation of health literacy observed in our study may require careful attention.

Strengths and limitations

This study is a first on HPV vaccine intention, which investigated both males and females of four college and university students in Japan. Our students included youth aged 18–35 years, and the majority fell into the 18–25 year age group in 2022 who had missed the opportunity to receive active promotion for routine immunization package by the government. The results of this study may be useful in understanding how much of the population may be willing to receive the HPV vaccine and in coming up with a strategy to promote the HPV vaccine for both males and females in the future.

Several limitations need to be addressed. First, our participants were recruited from four colleges and universities in Akita, but the participation rate varied and was heavily weighted on a national university to which our research team belonged. Second, it should be noted that the outcome of our study was vaccine intention and not actual vaccine uptakes. Third, this study was based on a cross-sectional investigation; thus, the causal differences in HPV vaccine behavior cannot be determined. Fourth, in our study, there might have been unmeasured confounding factors. For example, although the faculty of the health-care department was not associated with vaccine intention, a previous study suggested that trust in the healthcare system is an independent factor that impacts vaccine acceptance.⁴⁸ Hence, our results require careful interpretation.

Conclusion

At the end of 2021, the Japanese government resumed the active promotion of the HPV vaccine after nine years. Now we face new challenges on how to increase vaccine coverage, which had dropped to less than 1% during the suspension. Our results clearly demonstrated that there was a very low HPV vaccine acceptability among current college and university students who missed active recommendations from 2013 to 2021 in Japan. In addition, it was clear that both females and males had very low levels of knowledge of HPV infection, morbidity, transmission, and prevention. Our findings suggest that for males, HPV awareness campaigns, and for females, information to increase knowledge levels, including the safety and efficacy of HPV vaccines, may help increase vaccine acceptability.

Author contributions

T.S. (Tomoya Suzuki), K.N. (Kyoko Nomura), Y.O. (Yu Ota), N.F. (Nozomi Fujita), M.K. (Makoto Kamatsuka), J.H. (Junko Hirayama), K.S. (Kuniko Shiga), N. F. (Naoko Fujita), N.O. (Noriaki Oyama), Y.T. (Yukihiro Terada) collected the data; K.N (Kengo Nagashima) advised statistical analyses and calculated sample size. T.S., M.K. and N.F. analyzed the data; T.S., N.S. (Natsuya Sakata), and K.N. wrote the paper, which was reviewed and edited by K.N. All the authors read and approved the final manuscript. All authors have read and agreed to the published version of the manuscript.

Acknowledgments

We would like to thank Dr. Nagasaka, Dr Haruko Hiraike, Dr Hirono Ishikawa, Dr. Asuka Suzuki, Dr. Takeaki Takeuchi for initial recruitment in Tokyo, and Dr. Naoko Fujita for recruitment in Akita prefecture. We deeply appreciate all students in Akita University, Akita International University, Akita Prefectural University, Japanese Red Cross Akita College of Nursing who participated in our study.

Disclosure statement

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

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2022.2116900.

Additional information

Funding

This work was supported by Grants-in-Aid for Scientific Research [KAKENHI Grant Number 19K22737].