Assessing real world vaccine effectiveness: A review of Scotland's approach to monitoring human papillomavirus (HPV) vaccine impact on HPV infection and cervical disease.

High-risk human papillomavirus (HPV) infections can progress to cervical cancer which is the fourth most common cancer in women globally. In Scotland, the incidence of cervical cancer has a strong socioeconomic deprivation gradient disproportionately affecting women from more deprived areas. An HPV vaccination programme was initiated in Scotland in 2008 targeting girls aged 12-13 years with a catch-up campaign running for the first three years for girls aged up to 18 years. The programme has evolved over the last 16 years with changes in the type of vaccine, dosing schedules and the extension of the programme to boys and gay, bisexual and other men who have sex with men. Vaccine uptake in Scotland has historically been high but has gradually decreased over time and disparities exist in women from more deprived areas of Scotland. The ability to link national immunisation and screening databases in Scotland has allowed direct monitoring of the impact of the HPV vaccine on virological and histological outcomes. Analyses of this linked data have demonstrated real-world evidence of high vaccine effectiveness against HPV infection, cervical disease, and cervical cancer with evidence of herd immunity in unvaccinated women. Continued monitoring is crucial to assess the duration of protection, the impact of vaccine and dosing schedules changes and the emergence of potential type replacement. With the World Health Organisation's aim to eliminate cervical cancer as a public health problem by the next century addressing the inequalities in cervical cancer incidence will be crucial. This will require targeted interventions for women most at risk of cervical cancer to ensure elimination is achieved timely for all women in Scotland.

Invasive cervical cancer incidence following bivalent human papillomavirus vaccination: a population-based observational study of age at immunization, dose, and deprivation.

BACKGROUND: High-risk human papillomavirus causes cervical cancer. Vaccines have been developed that significantly reduce the incidence of preinvasive and invasive disease. This population-based observational study used linked screening, immunization, and cancer registry data from Scotland to assess the influence of age, number of doses, and deprivation on the incidence of invasive disease following administration of the bivalent vaccine. METHODS: Data for women born between January 1, 1988, and June 5, 1996, were extracted from the Scottish cervical cancer screening system in July 2020 and linked to cancer registry, immunization, and deprivation data. Incidence of invasive cervical cancer per 100 000 person-years and vaccine effectiveness were correlated with vaccination status, age at vaccination, and deprivation; Kaplan Meier curves were calculated. RESULTS: No cases of invasive cancer were recorded in women immunized at 12 or 13 years of age irrespective of the number of doses. Women vaccinated at 14 to 22 years of age and given 3 doses of the bivalent vaccine showed a significant reduction in incidence compared with all unvaccinated women (3.2/100 000 [95% confidence interval (CI) = 2.1 to 4.6] vs 8.4 [95% CI = 7.2 to 9.6]). Unadjusted incidence was significantly higher in women from most deprived (Scottish Index of Multiple Deprivation 1) than least deprived (Scottish Index of Multiple Deprivation 5) areas (10.1/100 000 [95% CI = 7.8 to 12.8] vs 3.9 [95% CI = 2.6 to 5.7]). Women from the most deprived areas showed a significant reduction in incidence following 3 doses of vaccine (13.1/100 000 [95% CI = 9.95 to 16.9] vs 2.29 [95% CI = 0.62 to 5.86]). CONCLUSION: Our findings confirm that the bivalent vaccine prevents the development of invasive cervical cancer and that even 1 or 2 doses 1 month apart confer benefit if given at 12-13 years of age. At older ages, 3 doses are required for statistically significant vaccine effectiveness. Women from more deprived areas benefit more from vaccination than those from less deprived areas.

Use of HPV testing for cervical screening in vaccinated women--Insights from the SHEVa (Scottish HPV Prevalence in Vaccinated Women) study.

The management of cervical disease is changing worldwide as a result of HPV vaccination and the increasing use of HPV testing for cervical screening. However, the impact of vaccination on the performance of HPV based screening strategies is unknown. The SHEVa (Scottish HPV Prevalence in Vaccinated women) projects are designed to gain insight into the impact of vaccination on the performance of clinically validated HPV assays. Samples collated from women attending for first cervical smear who had been vaccinated as part of a national "catch-up" programme were tested with three clinically validated HPV assays (2 DNA and 1 RNA). Overall HR-HPV and type specific positivity was assessed in total population and according to underlying cytology and compared to a demographically equivalent group of unvaccinated women. HPV prevalence was significantly lower in vaccinated women and was influenced by assay-type, reducing by 23-25% for the DNA based assays and 32% for the RNA assay (p = 0.0008). All assays showed over 75% reduction of HPV16 and/or 18 (p < 0.0001) whereas the prevalence of non 16/18 HR-HPV was not significantly different in vaccinated vs unvaccinated women. In women with low grade abnormalities, the proportion associated with non 16/18 HR-HPV was significantly higher in vaccinated women (p < 0.0001). Clinically validated HPV assays are affected differentially when applied to vaccinated women, dependent on assay chemistry. The increased proportion of non HPV16/18 infections may have implications for clinical performance, consequently, longitudinal studies linking HPV status to disease outcomes in vaccinated women are warranted.