Routine bivalent papillomavirus vaccination of girls aged 12-13 years in Scotland has been associated with a dramatic reduction in preinvasive cervical disease seven years later, research has shown. The authors of the study*, published in the BMJ, said there was also evidence of clinically relevant herd protection in unvaccinated women. And they argued that the reduction in disease in routinely immunised women, who will in the coming years form the bulk of the screened population, mandates revision of screening and referral guidelines.
A research team led from the University of Edinburgh conducted a retrospective population study, among 138,692 women born between 1 January 1988 and 5 June 1996 and who had a smear test result recorded at age 20, in order to quantify the effect on cervical disease at age 20 years of immunization with bivalent HPV vaccine at the age of 12-13 years.
They explained that Scotland introduced a national school-based immunisation programme against HPV in 2008 using the bivalent vaccine, which was used until 2012; this targeted girls aged 12 and 13 (routine vaccination – uptake consistently exceeding 85%), and was supplemented with a three-year catch-up programme to the age of 18 (uptake about 65% overall).
The researchers reported that compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 showed an 89% reduction in prevalent cervical intraepithelial neoplasia (CIN) grade 3 or worse (from 0.59% to 0.06%), an 88% reduction (83% to 92%) in CIN grade 2 or worse (from 1.44% to 0.17%), and a 79% reduction (69% to 86%) in CIN grade 1 (from 0.69% to 0.15%).
They added that younger age at immunization was associated with increasing vaccine effectiveness: 86% for CIN grade 3 or worse for women vaccinated at the age of 12-13, compared with 51% for women vaccinated at the age of 17.
They also observed herd protection for the unvaccinated women in the 1995-96 cohort, with a 63% reduction in the odds of CIN grade1, 67% reduction for CIN grade 2, and 100% reduction for CIN grade 3, compared with unvaccinated women in 1988-90; they saw similar reductions for moderate dyskaryosis/HSIL-M and high grade dyskaryosis/HSIL-H but not for borderline/ASCUS or low grade dyskaryosis/LSIL.
They commented: “Routine immunisation with three doses of bivalent vaccine at age 12-13 years is associated with a profound reduction of cervical disease seven years later, measured by cytological and histological abnormalities and referral for colposcopy. Disease was also reduced in unvaccinated women, possibly because of herd protection. Routinely vaccinated populations will also have a lower risk of other HPV related diseases. The reduction in disease in routinely immunised women, who will form the bulk of the screened population in years to come, mandates revision of screening and referral guidelines.”
The author of an accompanying editorial** pointed out that this study also highlights the value of integrated registries that can systematically collect and use high quality data from screening and vaccination programmes. She said: “Scotland has shown that integrated registry systems are highly effective tools in achieving and evaluating high vaccine uptake, and in assessing subsequent outcomes, including screening performance.”
She added: “These new data highlight that the bivalent HPV vaccine is still a good choice for cancer prevention and that, in countries such as Scotland, might even provide protection equivalent to the nonavalent vaccine,” which is not and might never be affordable for low-income countries.
*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: l1161, DOI:10.1136/bmj.l116.
**Brotherton JML. The remarkable impact of bivalent HPV vaccine in Scotland. BMJ 2019; 365: l1375 doi: 10.1136/bmj.l1375.