Human papillomavirus 16/18 vaccine recombinant bivalent(Xiamen Innovax)

Special attention has been paid to Hepatitis E (HE) prophylaxis for pregnant women due to poor prognosis of HE in this population. We conducted a post-hoc analysis based on the randomized, double-blind, HE vaccine (Hecolin)-controlled phase 3 clinical trial of human papillomavirus (HPV) vaccine (Cecolin) conducted in China. Eligible healthy women aged 18-45 years were randomly assigned to receive three doses of Cecolin or Hecolin and were followed up for 66 months. All the pregnancy-related events throughout the study period were closely followed up. The incidences of adverse events, pregnancy complications, and adverse pregnancy outcomes were analysed based on the vaccine group, maternal age, and interval between vaccination and pregnancy onset. During the study period, 1263 Hecolin receivers and 1260 Cecolin receivers reported 1684 and 1660 pregnancies, respectively. The participants in the two vaccine groups showed similar maternal and neonatal safety profiles, regardless of maternal age. Among the 140 women who were inadvertently vaccinated during pregnancy, the incidences of adverse reactions had no statistical difference between the two groups (31.8% vs 35.1%, p = 0.6782). The proximal exposure to HE vaccination was not associated with a significantly higher risk of abnormal foetal loss (OR 0.80, 95% CI 0.38-1.70) or neonatal abnormality (OR 2.46, 95% CI 0.74-8.18) than that to HPV vaccination, as did distal exposure. Significant difference was not noted between pregnancies with proximal and distal exposure to HE vaccination. Conclusively, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes.

Sub-Saharan Africa has the highest rate of cervical cancer cases and deaths worldwide. Kenya introduced a quadrivalent HPV vaccine (GARDASIL, hereafter referred to as GARDASIL-4) for ten-year-old girls in late 2019 with donor support from Gavi, the Vaccine Alliance. As Kenya may soon graduate from Gavi support, it is important to evaluate the potential cost-effectiveness and budget impact of the current HPV vaccine, and potential alternatives.

We used a proportionate outcomes static cohort model to evaluate the annual budget impact and lifetime cost-effectiveness of vaccinating ten-year-old girls over the period 2020-2029. We included a catch-up campaign for girls aged 11-14 years in 2020. We estimated cervical cancer cases, deaths, disability adjusted life years (DALYs), and healthcare costs (government and societal perspective) expected to occur with and without vaccination over the lifetimes of each cohort of vaccinated girls. For each of the four products available globally (CECOLIN©, CERVARIX©, GARDASIL-4©, and GARDASIL-9 ©), we estimated the cost (2021 US$) per DALY averted compared to no vaccine and to each other. Model inputs were obtained from published sources, as well as local stakeholders.

We estimated 320,000 cases and 225,000 deaths attributed to cervical cancer over the lifetimes of the 14 evaluated birth cohorts. HPV vaccination could reduce this burden by 42-60 %. Without cross-protection, CECOLIN had the lowest net cost and most attractive cost-effectiveness. With cross-protection, CERVARIX was the most cost-effective. Under either scenario the most cost-effective vaccine had a 100 % probability of being cost-effective at a willingness-to-pay threshold of US$ 100 (5 % of Kenya's national gross domestic product per capita) compared to no vaccination. Should Kenya reach its target of 90 % coverage and graduate from Gavi support, the undiscounted annual vaccine program cost could exceed US$ 10 million per year. For all three vaccines currently supported by Gavi, a single-dose strategy would be cost-saving compared to no vaccination.

HPV vaccination for girls is highly cost-effective in Kenya. Compared to GARDASIL-4, alternative products could provide similar or greater health benefits at lower net costs. Substantial government funding will be required to reach and sustain coverage targets as Kenya graduates from Gavi support. A single dose strategy is likely to have similar benefits for less cost.