In the UK, HPV vaccination of girls aged 12–13 as part of the school immunisation programme started in 2008 together with a three-year ‘catch-up’ programme’ for girls aged up to 18 years. Uptake rates for 3 doses in Scotland are high; almost 90% of girls eligible in the school programme and 65.5% in catch-up received all three doses. A national programme of longitudinal surveillance provides evidence on the impact and effectiveness of bivalent vaccine upon HR-HPV and CIN in routinely vaccinated girls and older catch-up women.
Until recently, Scotland began cervical screening at age 20 (though this was amended to the age of 25 in June 2016 to ensure consistency with other UK countries), and girls immunised as part of catch-up have been entering the screening programme since 2011. Thus, Scotland is almost uniquely placed to determine the impact of immunisation on cervical HPV infection, incidence of CIN, and genital warts in young women using national datasets, which can be linked effectively.
Of the women born in 1989 of whom 0.3% were immunised, 29.2% (26.7-31.9) were HPV 16/18 positive aged 20 compared to 4.5% (3.5-5.7) of women born in 1995 (87% of whom were immunised). Only ~0.5% (0.26-1.1) of the 1995 cohort tested HPV 16/18 positive with the clinically validated assay, compared to 21.4% (18.9-24.0) of unvaccinated women born 1989-1992. Prevalence of HPV 31, 33 and 45 reduced from 14.2% (95%CI: 12-16.7%) in the 1988 cohort to 2.6% (95% CI: 1.9-3.6%) in the 1995 cohort. Vaccine effectiveness (VE) was higher in the younger cohorts with VE=54.8% (95% CI: 36.7-67.7%) in the 1990 cohort, increasing to VE=85.7% (95% CI: 78.7-90.4%) in the 1995 cohort, illustrating slightly lower but comparable 3-dose vaccine effectiveness for the cross-protective types to the vaccine types. Analysis of the catch-up cohorts suggest profound impact upon CIN 3, with effect most noticeable in more deprived women (rate of CIN 3 in 1988 cohort being 11.9 per 1000 py (10.4-13.4) vs 2.9 per 1000 py (2-3.9) for the 1994 cohort.
HPV 16,18,31,33 and 45 are implicated in 84% of invasive cervical cancers and in Scotland these 5 HPV types account for 90% of cancers. For all 5 types, vaccine effectiveness in the 1995 cohort exceeded 80%, differing from recent meta-analysis which found evidence for HPV 31 cross-protection but little evidence for reductions of HPV 33 or 45. Encouragingly, there was no significant increase in non-16/18/31/33/45 HR-HPV types even though 16/18 prevalence has reduced by 6-fold (28.9% to 4.8%). Bivalent HPV immunisation has the potential to prevent up to 90% of infections that cause cervical cancer, with effects most notable in deprived women.