Impact of Bivalent HPV Vaccination in Scotland
A human papillomavirus (HPV) vaccine programme was introduced in Scotland in September 2008, targeting girls aged 12-13 years and additionally those aged up to 18 years from 2008 to 2011 as part of a catch-up programme. Women previously eligible, remain so until aged 25 years. The bivalent vaccine was utilised from 2008 to 2012, at which point the programme changed to using the quadrivalent vaccine. The percentage of girls who completed their HPV vaccine schedule remained above 90% in the routine cohort in the earlier years of the programme. This has fallen somewhat in recent years, albeit to just over 85% by the third year of school. This however may represent an underestimate as girls continue to be offered the vaccine throughout the school years. Scotland was well placed to evaluate the impact of the bivalent vaccine on infection and disease outcomes as women were invited for their first cervical screen at age 20 until 2016, meaning the impact of the catch-up programme could be assessed from 2010 and the routine programme from 2015.
High uptake of the vaccine has translated to dramatic reductions in the prevalence of HPV vaccine types 16 and 18 and HPV types 31, 33 and 45 which the bivalent vaccine confers a cross-protective effect against.1 Overall, HPV 16 and 18 prevalence in cervical samples taken at first screen was 30.0% in women born in 1988, who represented an unvaccinated cohort, compared to 4.5% in women born in 1995, who were offered vaccine routinely.1 Similar reductions in HPV prevalence have also been observed in equivalent non-vaccinated birth cohorts due to herd immunity. In women who have received 3 doses of bivalent vaccine at age 12-13 years, vaccine effectiveness against HPV 16 and 18 and HPV 31, 33 and 45 was 89.1% (95%CI, 85.1-92.3%) and 85.1% (95%CI, 77.3-90.9%) respectively (Figure 1).1
Reductions in HPV prevalence have pre-empted a clear and striking decrease of cervical abnormalities in both cytological and histological outcomes in vaccinated and non-vaccinated women in cohorts eligible for vaccination. As detailed in Palmer et al (2019) the impact of the bivalent vaccine on females aged 12-13 in Scotland was associated with a vaccine effectiveness of 93% (95%CI, 86-97%) for high-grade dyskaryosis and 86% (95CI%, 75-92%) against cervical intraepithelial neoplasia (CIN) grade 3 or worse.2 A 92% decrease in high-grade dyskaryosis and an 89% (95%CI, 81-94%) decrease in CIN 3+ has been observed in females aged 12-13 at vaccination compared to unvaccinated women.2 Additionally, decreases in all grades of histological abnormalities were observed in women born in 1995-96 who were not vaccinated compared to those unvaccinated and born in 1988, again highlighting evidence of herd immunity at the level of disease.2
It is clear from Scottish data that the HPV vaccine has had a major impact on both HPV infection and subsequent disease in vaccinated and unvaccinated women. These findings are consistent with global data, including in four Nordic countries where vaccine effectiveness is estimated to be above 90%.3 It is important to build on these successes, and with the introduction of a programme for gay, bisexual and other men who have sex with men (GBMSM) in 2017 and subsequently the universal HPV programme in Scotland in 2020 the beneficial impact of the HPV vaccine can be realised further. It is also crucially important to communicate and celebrate the success of the HPV vaccine in order to emphasise that the vaccine is both safe and highly effective. This is especially relevant in the context of vaccine hesitancy which has had a significant detrimental impact on vaccine uptake in Japan with 5000 preventable deaths predicted in the cohorts affected by the crisis.4
DISCLOSURE
KC’s institution has received research funding or gratis consumables to support research from the following commercial entities in the last 3 years: Cepheid, Genomica, LifeRiver, Euroimmun, GeneFirst, SelfScreen, Qiagen, Hiantis, Seegene and Hologic. The remaining authors have nothing to disclose.
ARTICLES INCLUDED IN HPW SPECIAL ISSUE ON HPV VACCINES:
Interview to EA Joura.
L Baandrup, P Valentiner-Branth, SK Kjaer. HPV vaccination crisis and recovery: the Danish case
B Huber, RBS Roden, R Kirnbauer. L2-based Human Papillomavirus Vaccines: Current Status And Potential
M Drolet, M Brisson. Population-level Impact and Herd Effects of HPV Vaccination Programs in High-Income Countries: Real-life Data
SM Garland, GL Murray, DA Machalek. Prevention of HPV-Related Diseases Following 4-Valent Vaccination in Australia
M Kane, M Stanley. Pre-school HPV Immunization?
PM Kotulka, A Luxembourg, A Shaw. Challenges in HPV Vaccine Development and Supply
QY Yan, MJ González-Méndez, YL Qiao. Current status of HPV vaccine in China
L Xu, SM Garland, M Arbyn. Efficacy of HPV Vaccination To Prevent Vulvar and Vaginal Precancer
References
1. Kavanagh K, Pollock KG, Cuschieri K et al. Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study. Lancet Infect Dis 2017;17(12):1293-302. https://pubmed.ncbi.nlm.nih.gov/28965955/
2. Palmer T, Wallace L, Pollock KG et al. Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study. BMJ 2019;365:1161. https://pubmed.ncbi.nlm.nih.gov/30944092/
3. Kjaer SK, Nygard M, Dillner J et al. A 12-Year Follow-up on the Long-Term Effectiveness of the Quadrivalent Human Papillomavirus Vaccine in 4 Nordic Countries. Clin Infect Dis 2017;66(3):339-45. Available from: https://pubmed.ncbi.nlm.nih.gov/29029053/
4. 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;5(4):e223-e234. Available from: https://pubmed.ncbi.nlm.nih.gov/32057317/
