Benefit-risk assessment of HPV vaccination programs in Australia, the United States, and Japan
Human papillomavirus (HPV) vaccination is a global strategy for the prevention of cervical cancer (CC). Although Australia and the United States (US) have achieved high coverage, the cumulative HPV rate of the first vaccination for Japanese females born in 2008 was approximately 55%, despite policy efforts. This study compared the situation in Japan with that in Australia and the US, where vaccination rates are higher. We conducted a unified benefit-risk assessment using disability-adjusted life year (DALY) rates to quantify the expected net value (ENV) of HPV vaccination programs per 100,000 eligible girls in Australia (2013-2020), the US (2013-2020), and Japan (2013-2024). Data on vaccination coverage, adverse events (AEs), and CC incidence were sourced from national health agencies and the Global Burden of Disease Study 2019. The vaccination coverage was 78.3% in Australia, 50.1% in the US, and 21.4% in Japan during the survey period. The ENV gained were 52.9 for Australia, 56.7 for the US, and 23.4 for Japan, reflecting differences in vaccination rates and CC burden. Across countries, the reporting rate of AEs was <0.05%, with most reports related to nervous system disorders and nonspecific symptoms. The benefit-to-risk ratio in Japan improved 7.9-fold after the resumption of active vaccination recommendations in 2021, largely owing to reduced reports of AEs. Japan's lower ENV gained compared to those of Australia and the US is primarily attributable to its low vaccination coverage and higher DALY rate for CC. HPV vaccination programs in Australia and the US have demonstrated strong benefit-risk profiles. Achieving vaccination rates comparable to those in Australia and the US can substantially improve outcomes. Japan's recent policy changes and educational initiatives have reduced AE concerns; however, further efforts are needed to raise the coverage of international benchmarks.