key: cord-0070746-pf7p6wje
authors: Sekine, Masayuki; Yamaguchi, Manako; Kudo, Risa; Hanley, Sharon J.B.; Ueda, Yutaka; Adachi, Sosuke; Kurosawa, Megumi; Miyagi, Etsuko; Hara, Megumi; Enomoto, Takayuki
title: Suspension of proactive recommendations for HPV vaccination has led to a significant increase in HPV infection rates in young Japanese women: real-world data
date: 2021-10-21
journal: Lancet Reg Health West Pac
DOI: 10.1016/j.lanwpc.2021.100300
sha: 903a66cb753c657ef05686c908b20b3584a1c505
doc_id: 70746
cord_uid: pf7p6wje

nan

We have expressed our concern about HPV vaccination coverage in Japan remaining below 1%, which will result in an increase in vaccine-targeted HPV infection rates and cervical cancer morbidity [1] [2] [3] [4] . Once again, we have been appealing for the resumption of proactive recommendations for HPV vaccination. Public funding for HPV vaccination became available for girls aged 13-16 years from 2010 in Japan and the vaccine was subsequently included in the national immunization program (NIP) for girls aged 12-16 years from April, 2013. In 2016, we calculated the risk of an HPV16/18 infection at age 20 years for birth cohorts eligible for HPV vaccination. While we predicted that HPV 16/18 infection rates would drop by about 30% in vaccinated cohorts, we also foresaw a future increase in unvaccinated cohorts due to suspension of proactive recommendations for the vaccine [3] . Vaccination coverage for Japanese girls decreased from 68.9% for those born in 1999 to 14.3% for those born in the year 20 0 0 [5] . In 2020, girls born in the year 20 0 0 reached the cervical screening age in line with the Japanese national cervical screening guidelines. Data from our screening program has shown that HPV 16/18 infection rates have indeed risen once again. This is the first report to document the real-world harms of the suspension of proactive recommendations for HPV vaccination in Japan in terms of increased infection of vaccine-targeted HPV types.

We investigated HPV infection rates in women aged 20-21 years undergoing cervical screening in Niigata City from April 2014 to March 2021 (fiscal years 2014-2020) [ HPV vaccinaƟon rate HPV 16/18 infecƟon rate According to previous survey data from Niigata, the HPV 16/18 infection rates in unvaccinated women aged 20-22 years was 2.2%, and it can be seen that the infection rate has increased again to almost the same level [7] . There was no significant difference in either "Age at sexual debut" or "Number of sexual partners" between the two groups (supplementary Figure 2, 3) . Suspension of proactive recommendations for HPV vaccination has real world public health consequences. WHO made a statement in 2015 that Japan's policy decisions based on weak evidence, leading to lack of use of safe and effective vaccines, can result in real harm [8] , and that has become a reality.

This result may not come as a shock to scientists, but how does the Japanese government feel about it? Although it is a radical expression, it can be said that they are conducting a real-world clinical trial on Japanese women. It goes without saying that an increase in HPV 16/18 infections in women in their 20s will lead to an increase in cervical precancers and cancers in women in their 30s and 40s in the near future. We urge the government to focus on the results and take urgent action to resume the proactive recommendations for the vaccine. However, in the current climate where safety concerns have spread among the public, it is unlikely that vaccination coverage will improve immediately due to the characteristics of Japanese people who are easily influenced by the decisions of those around them. If the vaccine crisis continues, approximately 10 0 0 0 preventable deaths due to cervical cancer are estimated to occur in the next 50 years (2020-69) [1] .

As Ueda and Tanaka et al. stated previously in the Lancet journal, when the Ministry of Health, Labour and Welfare resumes proactive encouragement, the following actions are required [ 2 , 9 ] : Enlightenment activities using a behavioral economics approach, accurate and scientific information dissemination in the media, policies for catch-up vaccination, introduction of 9-valent vaccine to NIP, and vaccination for boys to achieve herd immunity. We hope that the new Japanese Cabinet, in addition to its policy on COVID-19 infection, will significantly change its thinking about HPV vaccination to save the lives of Japanese women. 

Manako Yamaguchi, Yutaka Ueda, and Takayuki Enomoto received lecture fees from Merck Sharp and Dohme. Etsuko Miyagi received honoraria and lecture fees from Roche Diagnostics, Merck Sharp and Dohme, and Hologic Japan. All other authors report no potential conflicts.

Impact of HPV vaccine hesitancy on cervical cancer in Japan: a modelling study

Beyond resumption of the Japanese Government's recommendation of the HPV vaccine

Outcomes for girls without HPV vaccination in Japan

HPV vaccination crisis in Japan

Corrected human papillomavirus vaccination rates for each birth fiscal year in Japan

Epidemiologic Profile of Type-Specific Human Papillomavirus Infection after Initiation of HPV Vaccination

Bivalent Human Papillomavirus Vaccine Effectiveness in a Japanese Population: High Vaccine-Type-Specific Effectiveness and Evidence of Cross-Protection

Global Advisory Committee on Vaccine safety Statement on Safety of HPV vaccines

Time to resume active recommendation of the HPV vaccine in Japan

We would like to thank Ms. Yuka Watanabe, Ms. Sachiko Ono, Ms. Anna Ishida, and administrator of Niigata city for their support in conducting the survey. This work was supported by the Japanese Agency for Medical Research and Development (JP15ck0106103).

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.lanwpc.2021.10 030 0 .