Gardasil 9 is indicated for active immunisation of individuals from the age of 9 years against cervical, vulvar, vaginal and anal premalignant lesions and cancers causally related to vaccine HPV high risk (HR) types 16, 18, 31, 33, 45, 52 and 58. Gardasil 9 is anticipated to protect against the HPV types causing +- 90% of cervical cancers (CCs). The aim of this work was to estimate at individual level the residual country specific cumulative risk (CSCR) for developing CC and the risk of death from CC for an HPV naïve girl, unvaccinated or vaccinated with Gardasil 9 at the age of ten (i.e. considered HPV naïve), assuming lifelong vaccine protection and in absence of screening.
We used historical pre-screening age-specific CC incidence data from Denmark, Finland, Sweden and UK to calculate the CSCR of CC and mortality after vaccination with Gardasil 9 in the hypothetical absence of screening. To calculate the residual CSCR, the vaccine efficacy (VE) of 98.2% (95% CI: 93.5-99.8) for genotypes 16-18 and 97.1% (95%CI: 83.5-99.9) for the 5 additional HR types 31, 33, 45, 52 and 58 and genotype contribution fractions were used. To account for the uncertainty in incidence rates, VE estimates and genotype contribution fractions, a Monte Carlo simulation model was built. Instead of using historical mortality rate, we calculated the mortality ratio using the most recent data on CC incidence and the related mortality rate.
In absence of cervical screening, the CSCR of CC up to the age of 75 for unvaccinated girls varies from 1/31 [95% IC 1/29;1/34] (Denmark ) to 1/76 [95% IC 1/73;1/78] (UK). For a girl vaccinated with Gardasil 9, the residual CSCR of developing CC is substantially reduced, with estimates from 1/238 [95% IC 1/171;1/314] (Denmark) to 1/572 [95% IC 1/413;1/748] (UK). Similarly, the CSCR of CC related mortality for unvaccinated girls varies from 1/117 [95% IC 1/93;1/149] (Denmark) to 1/205 [95% IC 189 ; 223] (UK); and reduces to values from 1/887 [95% IC 1/600;1/1268] (Denmark) to 1/1553 [95% IC 1/1114;1/2048] (UK) after vaccination.
Our simulation estimates that vaccination with Gardasil 9 before the age of HPV exposure reduces the individual life-time risk of cervical cancer and cervical cancer related mortality in European settings to very low levels. If applied to countries with cervical screening programs (notably HPV based) the reduction in risk would be greater, since HPV screening should identify precancerous lesions due to non-vaccine HPV types. In addition to the simulation modelled above, Gardasil 9 is anticipated to protect between 80% to 95% against HPV-related vulvar, vaginal and anal cancers, for which there is no screening program.