Funding for human papillomavirus (HPV) vaccination in Japan began in 2010 for girls aged 12-16 years, with three-dose coverage initially reaching more than 70%.¹ On June 14, 2013, two months after formal inclusion in Japan's national immunisation programme (NIP), proactive recommendations for the HPV vaccine were suspended following unconfirmed reports of adverse events in the media. The vaccine remained free of charge for those in the target age-group, but doctors had to advise parents wishing to vaccinate their child that the government wasn’t actively recommending it. Vaccine coverage subsequently dropped to and remains at less than 1%.¹ Despite extensive evidence supporting the safety of HPV vaccination,² suspension of proactive recommendations by the Japanese government has continued now for more than seven years.

Given the long latency period between HPV infection and the diagnosis of invasive cancer, the long-term impact of suspension of proactive recommendations, in terms of morbidity and mortality due to cervical cancer and other HPV cancers, will not be seen for decades. Mathematical disease simulation models can estimate this impact by predicting preventable cancer diagnoses and deaths decades into the future. Therefore, we aimed to quantify the impact of the vaccine hesitancy crisis to date due to the Japanese government’s failing to proactively recommend HPV vaccination, as well as the potential health gains if coverage could be restored.

In this modelling study, we used the Policy1-Cervix modelling platform and adapted it for Japan using data on HPV prevalence, screening practices and coverage, and cervical cancer incidence and mortality. We evaluated the expected number of cervical cancer cases and deaths over the lifetime of cohorts affected by the vaccination program and subsequent suspension of the program (cohorts born from 1994 to 2007). We assessed a range of recovery scenarios from 2020 onwards, with the most favourable assuming that routine coverage is restored to 70%, with 50% catch-up coverage for the missed cohorts (aged 13–20 years in 2020) using the 9-valent HPV vaccine (HPV9). To estimate the impact of the vaccine crisis to date, we also modelled a counterfactual scenario in which 70% coverage had been maintained in 12-year-olds from 2013 onwards.

The HPV vaccine crisis in Japan from 2013 to 2019 is predicted to result in an additional 24,600-27,300 cases and 5,000-5,700 deaths over the lifetime of affected cohorts, compared with sustained vaccination coverage at around 70% since 2013. Restoration of coverage in 2020, including catch-up vaccination for missed cohorts with HPV9, could prevent 20,300 of these cases and 4,100 deaths, and therefore most of the deaths due to the crisis could be prevented (Table 1). If coverage is not restored in 2020, an additional 3,400-3,800 cases and 700-800 deaths will occur over the lifetime of individuals who are 12 years old in 2020 alone, approximating the preventable cancers and deaths that will result from every year that coverage remains low. If the HPV vaccination crisis continues, 55,800-63,700 preventable cases and 9,300–10,800 preventable deaths due to cervical cancer will occur in the next 50 years (2020–69) (Table 1).³

Because of the instant and wide-ranging influence of social media, suspension of proactive recommendations for the HPV vaccine in Japan probably contributed to vaccine hesitancy crises in both Denmark and Ireland. However, governments in both these countries acted quickly by addressing safety concerns and uptake recovered.^4,5 A strong and timely response to reports of adverse events is essential to sustain and rebuild public trust in vaccines.

We estimate that vaccination delivered in Japan prior to the crisis will prevent at least 3,000 cervical cancer deaths in the longer term – but also that HPV vaccine hesitancy in Japan to date will result in around 5,000 avoidable cervical cancer deaths, and this number will increase by around 700–800 for each year the crisis continues.³ Many of these deaths could still be prevented if vaccination coverage with extended catch-up and HPV9 was rapidly restored. The time to act is now. On July 21st, 2020, the nonavalent HPV vaccine was approved for use in Japan, 5 years after it was initially submitted for licensing. It is expected that the government will include it in Japan’s NIP from next year. However, providing the vaccine free of charge is not enough. High-level political support for HPV vaccination needs to be restored and proactive recommendations reinstated.

Finally, it is important to note that rapid restoration, plus catch-up with nonavalent HPV vaccine alone will not lead to the WHO elimination target of <4 per 100,000 cases in Japan by the end of the century (Figure 1): increasing screening coverage is also necessary.

References

1. Hanley SJ, Yoshioka E, Ito Y, Kishi R. HPV vaccination crisis in Japan. Lancet 2015; 385(9987): 2571. Available from: https://pubmed.ncbi.nlm.nih.gov/26122153/

2. WHO. Safety update of HPV vaccines. 2017. Available from: https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/human-papillomavirus-vaccines/safety (accessed June 11 2021).

3. Simms KT, Hanley SJB, Smith MA et al. Impact of HPV vaccine hesitancy on cervical cancer in Japan: a modelling study. Lancet Public Health 2020. Available from: https://pubmed.ncbi.nlm.nih.gov/32057317/

4. Corcoran B, Clarke A, Barrett T. Rapid response to HPV vaccination crisis in Ireland. Lancet 2018; 391(10135): 2103. Available from: https://pubmed.ncbi.nlm.nih.gov/29856339/

5. Hansen PR, Schmidtblaicher M, Brewer NT. Resilience of HPV vaccine uptake in Denmark: Decline and recovery. Vaccine 2020; 38(7): 1842-8. Available from: https://pubmed.ncbi.nlm.nih.gov/31918860/