In Japan, government subsidies for human papillomavirus (HPV) vaccination of girls aged 13–16 commenced in 2010. By early 2013, vaccination had become a widely accepted national immunization program. However, in June of 2013, the Ministry of Health, Labor, and Welfare (MHLW), the government’s lead agency, suspended its recommendation for vaccination in response to reports of adverse vaccine events. The rate of HPV vaccination quickly dropped from 70% to almost zero, where it has lingered for eight years. In 2020, a new 9-valent HPV vaccine was licensed in Japan. The momentum seemed to be building for the resumption of HPV vaccinations, yet Japanese mothers remain widely hesitant about vaccinating their daughters, despite the well-proven safety and efficacy of the HPV vaccines.
HPV vaccine;cervical cancer;government suspension of recommendation
Cervical cancer is one of the most common cancers for women. In 2020, an estimated 600,000 women were diagnosed with cervical cancer worldwide, and about 341,000 deaths were attributed to it 
. On a global scale, Japan has been classified as having a moderate age-standardized incidence rate of cervical cancer; India, Nigeria, and other countries belong to this moderate group as well. Interestingly, China, Korea, Russia, and Brazil have a lower incidence rate. The World Health Organization (WHO) has noted that the burden of cervical cancer typically falls most heavily on women who lack proper access to health services, mainly those in low-and middle-income countries 
, thus, it is disconcerting that among the most developed countries of the world, Japan’s incidence rate of cervical cancer has been accelerating since 2000 (Age-adjusted rate: 28.0 in 1976, 9.1 in 2000, 14.1 in 2012, Annual percent change in 2000–2012: 3.8 (95% CI: 2.7–4.8)) 
, a trend not seen in any other advanced country. In Japan, 10,978 women were diagnosed with cervical cancer in 2018; in 2019, 2921 died from it [4,5]
. Modern changes in sexual lifestyles and an increasing rate of smoking among women have clearly contributed to this national trend for increasing cervical cancer morbidity and mortality. Because Japan’s human papillomavirus vaccination (HPV) vaccination program was only started in 2010, the bulk of these cancers are occurring in an extended generation of unvaccinated women.
It is well established that the most critical risk factor for cervical cancer is having experienced a persistent infection with one of the high-cancer-risk versions of HPV 
. Persistent infection can lead to developing precancerous lesions that, if undetected and untreated, can progress to invasive cervical cancer. HPV has retrospectively been detected in most cervical cancers in Japan [7,8]
. The most frequent types attributed to causing cervical cancers are the HPV 16 and 18 strains, which together account for almost 60% of cervical cancers in Japan, which is significantly lower than the global average of 71% for HPV 16/18 [9,10]
. Heavy smoking, long-term use of oral contraceptives, and promiscuous sexual experiences at a young age are contributing risk factors [11,12,13]
Most cervical cancers are primarily preventable by an effective HPV vaccination. Secondary prevention approaches include early and consistent screening for and treatment of precancerous lesions. Almost inexplicably, although Japan has in hand all the technical, medical, policy, and fiscal tools with which to eliminate cervical cancer, they are almost totally failing to do so.
Among its many problems is cervical cancer screening, which in Japan is recommended for all women over the age of 20. Incredibly, the screening rates for young women within three key age groups, of 20–24, 25–29, and 30–39, are only 10%, 10–20%, and 10–30%, respectively 
. Forty-two-point-four percent of Japanese women aged 20–69 had a Pap smear in the past two years, while 60.7% of target women had Pap smear in the past three years on average across OECD countries 
. Furthermore, Japan’s once enviable 70% HPV vaccination rate has fallen to almost zero 
, making Japan an outlier among the developed nations.
2. Politics, Policies, and Events Related to HPV Vaccinations
We would like to share some relevant background information, some insights on the current states of HPV vaccinations and cervical screening in Japan, and give some consideration as to what directions Japan is now moving. We begin by noting that the quadra-valent HPV vaccine was approved in 2006 in the United States of America, the European Union, and Australia, and by 2020, it had been approved in more than 130 countries 
. The new broader-spectrum 9-valent vaccine has already been approved in more than 80 countries 
. In 2018, the Director-General of WHO called for a global action to eliminate cervical cancer. In 2020, the World Health Assembly adopted its Global Strategy to accelerate the elimination of cervical cancer as a public health problem, which has since been adopted by many countries 
shows a brief history of HPV vaccination in Japan. Here are some of the high points. In October of 2009, the bivalent HPV vaccine was the first to be cautiously licensed in Japan; licensing the quadra-valent form followed two years later, in July 2011, a full five years after it had been widely accepted elsewhere. Subsidies from local and national government programs for HPV vaccination of girls aged 13–16 commenced flowing in November of 2010. By April of 2013, both the bi-valent and quadra-valent HPV vaccines were being used routinely for vaccinating girls aged 12–16 as part of the National Immunization Program.
Table 1. Timeline of the policies and events related to HPV vaccines in Japan.
||The bi-valent HPV vaccine was licensed.
||Subsidies from local and national governments for an HPV vaccination program for girls 13–16 commenced.
||The quadra-valent HPV vaccine was licensed.
||The national immunization program for girls aged 12–16 years commenced
||The VARRC ruled that “It is necessary to determine the frequency of pain occurrence whose relationship can be undeniably linked to HPV vaccination. HPV vaccination should not be actively recommended until proper information can be provided to the public.” The VARRC announced the suspension of its recommendation for vaccination (Notification by the Director-General of the Health Service Bureau of the MHLW).
||January and July
||The VARRC evaluated the pathogenesis and causal relationship of the “diverse symptoms” reportedly experienced after HPV vaccination. The reported chronic pain and motor impairment were regarded as functional physical symptoms (a form of functional somatic syndrome).
||The “Guide for the Management and Treatment of Symptoms that Occur after HPV Vaccine Injection” was published. An organization of cooperative medical institutions from all 47 prefectures agreed to provide treatment for any girl suffering from symptoms after HPV vaccination in any community throughout Japan. The MHLW announced three measures for patients with symptoms, mainly of pain or movement disorders.
||The result of the adverse events follow-up survey was released. The suspension of governmental recommendation was continued. The MHLW and the Ministry of Education, Culture, Sports, Science, and Technology issued their “Improvement of the Consultation and Support System for Persons with Symptoms after HPV Vaccination”. Relief (subsidies for medical expenses, etc.) based on the Immunization Law and the Pharmaceuticals and Medical Devices Agency Law, was implemented
||Symptom consultation services were established in the health and education departments of each prefecture.
||The VARRC evaluated the safety and efficacy of HPV vaccines in Japan and abroad.
||The conclusions of a nationwide epidemiological survey by a research team designated by the MHLW were reported to the VARRC (Key finding: Unvaccinated girls had a similar number of “diverse symptoms”).
||The VARRC evaluated all available information on the safety and efficacy of the HPV vaccine in Japan and abroad and expressed its commitment to continue to provide close support to patients who presented with any of the diverse symptoms. The VARRC discussed ways to better inform the public about the HPV vaccine.
||An extensively revised informational leaflet was released by the MHLW to better inform the public about the HPV vaccine.
||The VARRC reported the results of a survey on the provision of HPV vaccine information.
||The “Parliamentary Association for the Resumption of Recommendation of HPV Vaccination” submitted a petition to the MHLW. The 9-valent HPV vaccine was licensed in Japan.
||MHLW’s ‘Leaflet to Inform the Public about the HPV Vaccine’ was revised.
||The quadra-valent HPV vaccine was approved to prevent anal cancer for males.
||“Parliamentary Association for the Resumption of Recommendation of HPV Vaccination” submitted a petition to the MHLW again. The Japanese Society of Obstetrics and Gynecology submitted a petition to the MHLW to extend the period of routine vaccination.