Disparities among Japanese municipalities in recommendations for routine and catch-up HPV vaccinations

Abstract

In November 2021, the government of Japan announced a reversal of its decision in 2013 to suspend the previous proactive recommendation for HPV vaccination. However, the program for young girls to receive routine and catch-up vaccinations has not necessarily developed as expected. We conducted a nationwide questionnaire survey by mail in September 2022. The survey was mailed to 133 municipalities consisting of all cities/wards of the Tokyo and Osaka Prefectures and all other prefectural capital cities. Responses were received from 82 municipalities (62.7%). Notification of routine HPV vaccinations had already been sent to 76 (92.7%) of the municipalities; 70 (85.4%) had been encouraged to promote catch-up vaccinations. The questionnaire forms for registration and pre-vaccination screening for routine immunization had been sent to 74.1% (60/81) of the municipalities and 68.8% (55/80) for catch-up immunizations. For catch-up vaccination, only 54 municipalities (65.9%) had detailed vaccination records for those eligible. In total, 10 municipalities (12.2%) had virtually no vaccination records because these had already been discarded. In addition, 61 municipalities (74.4%) had notified only women and girls eligible for a catch-up vaccination based on their vaccination record, whereas 25.6% (21/82) of the municipalities reported that they had sent, or would send, the notification to all women and girls within the targeted grades, including those who had already been vaccinated with three injections. The survey revealed disparities among the municipalities in their HPV vaccine notification processes. Future research on monitoring HPV vaccination rates and incidence rates of cervical cancer and precancerous lesions in each municipality will be desirable.

Abbreviations
• FY
• fiscal year
• HPV
• Human papillomavirus
• MHLW
• Ministry of Health, Labor, and Welfare

INTRODUCTION

HPV vaccination has become routine in 130 countries around the world. In Japan, administration of the bivalent HPV vaccine was launched in December 2009 and of the quadrivalent vaccine began in August 2011; public subsidies for vaccination of 7th to 10th grade girls were introduced in November 2010. The national vaccination rate had approached ~70%,^1,2 and routine vaccination for girls from the 6th grade to 10th grade was started in the FY 2013.

The age-adjusted incidence of cervical cancer in Japan had recently begun to increase, so there were optimistic expectations for significant cervical cancer reductions following the adoption of the HPV vaccine.³ However, just 2 months later, in June 2013, the MHLW announced a “temporary” suspension of its proactive vaccination recommendations due to reports of adverse post-vaccination events. The suspension resulted in a precipitous drop in Japan's vaccination rate, from 70% to less than 1%.⁴ In response, the World Health Organization (WHO) stated “to date, it has not found any safety issue that would alter its recommendations for the use of the vaccine” and it condemned the Japanese government's overcautious response, saying that their policy decisions, based on weak evidence, and leading to the lack of use of safe and effective vaccines, could result in real harm. Supportive of this prediction, HPV infections and cervical cytology abnormality rates found during routine cervical cancer screenings in Japan increased among the 20-year-olds belonging to the generation of girls in which vaccination rates had dropped. These rates increased, returning to the same levels as for those of the generation of girls before the HPV vaccine was ever introduced.^5,6

During this period of vaccine rejection here in Japan, solid scientific data on the prevention of cervical cancer achieved via the HPV vaccine has been accumulating in other countries. A significant reduction in cervical cancer was demonstrated in several population-based studies.^7–9 In Japan, the preventive effect of the vaccine for HPV infection and precancerous lesions of the cervix was also reported.^10–13

In November 2021, 8 years and 6 months after the suspension of its proactive recommendation for the HPV vaccine, the national government announced an end to the suspension. Effectively, its proactive recommendation for routine HPV vaccination was resumed to local governments nationwide and a new program for catch-up vaccinations was started in April 2022.

However, the program for young girls to receive routine and catch-up vaccinations has not necessarily developed as expected. If the current low vaccination rate does not increase, women will continue to become infected with HPV and contract cervical cancer, and many will lose their lives, all of which could have been so easily prevented.¹⁴

During the period when HPV vaccine recommendations were withheld, local governments across the country also stopped providing HPV vaccine information to eligible girls and their parents or guardians. A 2018 MHLW survey found that only 5.6% of local governments across Japan had sent HPV vaccine information to eligible individuals or their guardians.¹⁵

For the study described below, we conducted a nationwide questionnaire survey of local municipal governments to investigate the point-in-time status of their HPV vaccine recommendations. The study was conducted soon after the resumption of the government's proactive recommendation for routine and catch-up HPV vaccination.

MATERIALS AND METHODS

In September 2022, a questionnaire survey was conducted by mail to all the cities/wards in the prefectures of Tokyo and Osaka, and to all the prefectural capital cities in Japan, a total of 133 municipalities. The survey asked them to document the status of their ongoing notifications to girls of routine vaccinations and catch-up vaccinations, the materials used for notification, the recipients of the notification, the timing of the notification, and whether or not a recall (re-notification to those who had not been vaccinated) had been, or would be, conducted. In addition, the management of vaccination records in each municipality was also investigated.

RESULTS Routine vaccination Status of notifications and the form of the registration and pre-vaccination screening questionnaire sent

Responses were received from 82 of the 133 municipalities that were sent surveys (62.7%) (Table S1). At the time of the response, 76 municipalities (92.7%) had already sent girls a notification regarding routine vaccinations; the remaining 6 (7.3%) had either partially sent or were planning to send a notification (Table 1). The most common mailing date was April 2022, at 35.0% (28/80). Most municipalities (79; 96.3%) used either the leaflets prepared by the MHLW or their leaflets for notification. In particular, leaflets prepared by the MHLW were used in 73 municipalities (89.0%), including those enclosed with the municipalities' own leaflets. In total, 74.1% of the municipal respondents (60/81) sent the form of registration and pre-vaccination screening questionnaire. One municipality did not answer this question. Only eight municipalities (8/81; 9.9%) responded that they planned to recall those who had not received their routine vaccinations during their previous time of normal eligibility.

TABLE 1 Status of notifications and the form of registration and pre-vaccination screening questionnaire sent.

	Routine vaccination		Catch-up vaccination
Status of notification sending
Already sent	78	(92.7%)	70	(85.4%)
Partially sent	2	(2.4%)	2	(2.4%)
Will send	4	(4.9%)	10	(12.2%)
Won't send	0	(0.0%)	0	(0.0%)
Documents sent
MHLW leaflet	53	(64.6%)	51	(62.2%)
Original leaflet	6	(7.3%)	4	(4.9%)
Both	20	(24.4%)	22	(26.8%)
Others	3	(3.7%)	5	(6.1%)
Sending a form of registration and pre-vaccination screening questionnairea
Yes	60	(74.1%)	55	(67.9%)
No	21	(25.9%)	25	(30.9%)
Undecided	0	(0.0%)	1	(1.2%)
Total	81	(100%)	81	(100%)

Abbreviation: MHLW, Ministry of Health, Labor and Welfare.

^aMunicipalities that did not answer were excluded from the analysis.

Recipients

Forty municipalities (48.8%) sent vaccine-eligibility notices to all girls in currently eligible grades (born between FY 2006 and FY 2010), and 34 municipalities (41.5%) responded that they had sent the notices to a smaller target population, excluding 6th graders (born in FY 2006) (Table 2).

TABLE 2 Information on recipients, timing of sending, and recall.

	Routine vaccination			Catch-up vaccination
Birth FY for which recommendation was sent/will senda	2006–2010	40	(48.8%)	1997–2005	79	(100%)
	2006–2009	34	(41.5%)
	Others	8	(9.8%)
	Total	82	(100%)	Total	79	(100%)
Month to start sendinga	July 2021	1	(1.3%)	July 2021	1	(1.2%)
	Feb 2022	2	(2.5%)	Dec 2021	1	(1.2%)
	Mar 2022	18	(22.5%)	Mar 2022	1	(1.2%)
	April 2022	28	(35.0%)	April 2022	5	(6.2%)
	May 2022	14	(17.5%)	May 2022	12	(14.8%)
	Jun 2022	9	(11.3%)	Jun 2022	25	(30.9%)
	July 2022	5	(6.3%)	July 2022	19	(23.5%)
	Aug 2022	1	(1.3%)	Aug 2022	13	(16.0%)
	Sep 2022	2	(2.5%)	Sep 2022	4	(4.9%)
	Total	80	(100%)	Total	81	(100%)
Recalla
Scheduled	8	(9.9%)		2		(2.5%)
Not scheduled	26	(32.1%)		23		(29.1%)
Undecided	47	(58.0%)		54		(68.4%)
Total	81	(100%)		79		(100%)

^aMunicipalities that did not answer were excluded from the analysis.

Catch-up vaccination Status of notifications and the form of registration and pre-vaccination screening questionnaire sent

At the time of their response, 70 municipalities (85.4%) had already sent notification of eligibility for catch-up vaccinations, and the remaining 12 (14.6%) had either partially sent or were planning to send these notifications (Table 1). The most common date was June 2022, at 30.9% (25/81) (Table 2).

Most municipalities (77/82, 93.9%) used leaflets prepared by the MHLW or their notices. In 22/82 (26.8%), both leaflets were used. In total, 67.9% (55/81) of the municipalities that responded had already sent the form of registration and pre-vaccination screening questionnaire.

Two of the 82 municipalities (2.4%) responded that they planned to recall those eligible to receive a catch-up vaccination; however 23 (29.1%) had no intention to do so and 54 (68.4%) were undecided (Table 2). In addition, except for two municipalities that did not respond, 23.8% (19/80) responded that they would provide a different cervical cancer screening recommendation than usual to those eligible for catch-up vaccination (data not shown).

Recipients

Only 54 municipalities (65.9%) had retained accurate vaccination records for all eligible ages, including the type of vaccine, number of vaccinations, and whether they were interrupted; 10 municipalities (12.2%) had already discarded their vaccination histories (Table 3).

TABLE 3 Immunization record kept and subject extraction

Immunization records kept	Actual recipients of notification
	Subjects extracted from vaccination records	All relevant birth FYs
Kept a detailed vaccination history	49/54 (90.7%)	5/54 (9.3%)
Kept partial vaccination history	12/18 (66.7%)	6/18 (33.3%)
Discarded vaccination history	–	10/10 (100%)

Abbreviation: FY, fiscal year.

Using detailed or partial vaccination data, 61 of the 82 municipalities (74.4%) had notified as many women as possible who might be eligible for catch-up vaccination. Conversely, 25.6% (21/82) of the municipalities responded that they would send a notification to all women and girls in the relevant birth FYs, including women who had already been vaccinated three times. In detail, 9.3% (5/54) of the municipalities that kept detailed vaccination records, 33.3% (6/18) that kept partial vaccination records, and 100% (10/10) that had discarded vaccination records carried out this type of blanket notification (Table 3).

Keeping vaccination records

A survey was also conducted on the retention of vaccination records for all vaccines in general. For the general retention period, 60 (89.6%) of the 67 municipalities that responded indicated that they kept vaccination records for 5 years, and 5 (6.1%) indicated that they kept them permanently. However, only 20 (26.7%) of the 75 responding municipalities indicated that they destroyed their immunization records after 5 years, while 70.1% (53/75) indicated that they kept at least some information for more than 5 years (Table 4).

TABLE 4 Status of retention and destruction of immunization records

	Number of municipalities (%)
Policy of retention period of vaccination historya
5 years	60	(89.6%)
Permanent	5	(7.5%)
Others	2	(3.0%)
Total	67	(100%)
Actual management status of HPV vaccination historya
All discarded in 5 years	20	(26.7%)
Keep some of the information	53	(70.7%)
Others	2	(2.7%)
Total	75	(100%)

^aMunicipalities that did not answer were excluded from the analysis.

DISCUSSION

We had a mediocre response to our survey, as only 82 of the 133 municipalities across Japan that were sent our questionnaire responded, with a response rate of 62.7%. However, the combined population of these 82 municipalities was ~32.27 million, making this a reasonably large-scale survey covering approximately one-fourth of the entire country.

In an internet survey of men and women aged 12–69, conducted by the MHLW in October 2018, many respondents wanted their local government to provide them with information about the significance and effectiveness of the HPV vaccine. This was to supplement the information obtained from the media and their family doctors,¹⁵ suggesting that information provided by local governments regarding the HPV vaccine might have a significant impact on vaccination rates. When Isumi City in Chiba Prefecture provided HPV vaccine information to all their 10th grade girls in FY 2019 (while proactive recommendations were still suspended), the vaccination rate increased from 0% to 10.1%.¹⁶

In October 2020, the MHLW issued a notice to local governments nationwide to begin providing information regarding the HPV vaccine individually to both eligible girls and their guardians. According to a nationwide survey conducted by the MHLW in FY 2021, 61% of Japan's 1737 local governments sent HPV vaccine informational leaflets and other information to these individuals during FY 2020, with 10th grade girls the most common recipients.¹⁷ In the following FY 2021, 76% of local government respondents stated that they planned to send out an HPV vaccine leaflet, mostly to 7th grade girls, the standard primary target group for HPV vaccination. Disappointingly, 6% of the local governments responded that they would not be sending any HPV information.

The national vaccination rates for FY 2020 and FY 2021 (the FYs when individual notifications were first conducted) have not yet been published. However, our focused survey found that the vaccination rate in Toyonaka City increased significantly, reaching 16.5%, following their groundbreaking program of individual notifications in FY 2020, especially among girls born in FY 2004 (in 10th grade at the time).¹⁸ In addition, analysis of data provided by local governments in the Osaka Prefecture showed that the HPV vaccination rates increased even in school grades in which no individual guidance was provided, suggesting that society's acceptance of the HPV vaccine was expanding, although the effect had limitations, as the increases in vaccination rates were highest in those grades in which individual notifications were conducted.¹⁹

Our survey results informed us how important it is for the vaccine-targeted populations of girls to receive reliable and effective vaccine information from local governments. It is somewhat worrisome that the type and flow of such information received, if any, differed greatly, depending on municipality residency. This disparity in information may also be true for routine HPV vaccinations, for which proactive recommendation resumed in this FY, and for catch-up vaccinations that started later in this FY. There are serious concerns that differences in the way vaccine-eligibility notifications are distributed among local governments may detrimentally affect vaccination rates.

Conversely, most municipalities (89%) used leaflets prepared by the MHLW for notification, indicating that MHLW's materials were useful to them. Although there were various differences in notification methods among municipalities, modification or revision of the MHLW's leaflet, as a notification material, may lead to some uniform effects by increasing vaccination coverage.

In the current catch-up immunization program, women (born between FY 1997 and FY 2005) who were never vaccinated during the suspension period, or who did not complete immunization with all three recommended doses of the HPV vaccine, are eligible for free vaccinations. Women with interrupted vaccinations are to receive their remaining number of doses, using the same type of vaccine product given previously.

However, our survey found that at least 12% of the responding municipalities had already discarded the relevant vaccination records, i.e., records indicating which type of vaccine and how many doses had been administered. Even in municipalities where detailed vaccination records had been kept, 9% had sent unneeded catch-up vaccination notices to women who had been previously fully vaccinated, i.e., three times. This could lead to inappropriate vaccinations.

Although overvaccination is likely to be harmless, corrective notices should be mailed as soon as possible. The memories of the patient cannot be trusted. In a survey conducted in Niigata City, discrepancies between a woman's self-reported vaccination status and her official HPV vaccination records were found in 21% of cervical cancer screening subjects aged 20–22.²⁰ In particular, 46% of the women who thought they had never been vaccinated against HPV had been given the vaccine, according to their official vaccination records.

Thus, for the reasons discussed above, it is likely that under the catch-up program, many young women will be unnecessarily vaccinated four or more times. The current target age range for catch-up vaccination is 17–27 years old, so it is easy to imagine that vaccine records could not be confirmed due to loss of the maternal and child health handbook, or for other reasons.

The retention period for HPV vaccination records required by law for municipalities is 5 years. In this survey, most municipalities (89.6%) also indicated that the general retention period for records for all vaccines was 5 years. It is interesting to note, however, that only 26.7% of the municipalities destroyed their vaccination records after 5 years. Unless the required retention time for vaccination records in Japan is significantly extended well beyond 5 years, it will be difficult in the future to connect the occurrence of invasive cervical cancer with the failure to receive routine and catch-up protective HPV vaccines. It is now possible to store and easily retrieve enormous amounts of data on electronic media. Vital health information useful for epidemiological studies, including vaccination histories, can and should be stored (under strict confidentiality security) for many years.

One limitation of our study is that the survey was conducted only in the municipalities of all the cities/wards in the prefectures of Tokyo and Osaka, as well as all the prefectural capital cities in Japan. Therefore, the results may be limited to urban areas and may have a selection bias. In the next study, we would like to investigate the actual situation including the rural areas that were not covered in this survey. However, when considered on a population basis, the survey covered nearly one-quarter of Japan's population, which led us to believe it reflected, to a certain extent, the actual situation across the nation.

The survey was conducted in September 2022, the beginning of FY 2022. It is possible that some municipalities have since changed their policies, so our results may not reflect the situation for the entirety of FY 2022. Last, our study did not examine vaccination coverage for routine and catch-up vaccinations in individual municipalities, nor did we analyze the relationship between the ways girls eligible for vaccinations were notified and their subsequent vaccination acceptance.

Of importance, this survey revealed troubling disparities among the nation's municipalities regarding HPV vaccine-eligibility notifications, suggesting that the health of our citizens may be detrimentally affected by the municipality in which they reside. Better governmental guidance to improve the uniformity of messages would be useful. Future surveys on HPV vaccination rates versus incidence rates of precancerous lesions and cervical cancer in each municipality are desirable.

ACKNOWLEDGMENTS

We would like to thank G.S. Buzard for his constructive critique and editing of our manuscript. We thank the government officials in 82 municipalities for their cooperation in responding to our questionnaire survey.

FUNDING INFORMATION

This study was supported by a Health and Labor Sciences Research Grant (K20EA10250) and also supported by AMED under Grant Number 22ck0106562h0003.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

ETHICS STATEMENTS

This study was approved by the Ethics Committee of the Osaka University Medical Hospital.

Approval of the research protocol by an Institutional Reviewer Board: N/A.

Informed Consent: Informed consent was obtained by checking the box “I agree to participate in this survey” by all the municipal participants in this study.

Registry and the Registration No. of the study/trial: N/A.

Animal Studies: N/A.