(A-122) The Effectiveness of HPV Vaccination in Women Younger Than 18 Years Old to Prevent HPV-Related Pre-Cancerous Lesions and Cancers: a UK Population-Based Cohort Study

Background: HPV is the main cause of cervical cancer and is associated with many other cancers and lesions.

Objectives: We aimed to evaluate the effectiveness of HPV vaccination in reducing oropharyngeal, vaginal, vulvar and anal cancers and cervical pre-cancerous lesions (CIN2+) and cancer among women vaccinated before their 18th birthday.

Methods: Cohort study using primary care data from UK CPRD GOLD, including females born >= 1990 and in observation from their 9th to 18th birthday. Vaccination status was based on >=1 dose of HPV vaccine before their 18th birthday (index date). To minimise confounding, we exact matched by year of birth, practice, year of vaccination, and by nearest-neighbour propensity score with 0.2 calliper. We estimated absolute standardised mean differences (ASMD) for all recorded covariates, and identified ASMD>0.1 as relevant imbalance. We analysed 39 Negative Control Outcomes (NCO) and used empirical calibration to reduce residual confounding. We studied cervical screening as a proxy for diagnostic effort. Vaccine effectiveness at 15 years (VE) was calculated as 1-RR, modelled using Poisson regression.

Results: Overall, 105,562 unvaccinated and 180,053 vaccinated women were included. Before matching, we found relevant imbalanced covariates (ASMD>0.1) including hormonal contraceptives. After NCO empirical calibration, crude VE (95% CI) was 91% (23%-99%) against cervical cancer and 44% (33%-54%) against CIN2+. Oropharyngeal, vulvar, vaginal, and anal cancers were too infrequent (n < 5 for each), precluding VE analysis. RR for cervical screening was 1.44 (1.36-1.52). After matching, 43,440 unvaccinated and 77,151 vaccinated were included, with no observed confounding (all covariates ASMD < 0.1). VE against CIN2+ in the matched population was 65% (43%-78%), with similar cervical screening uptake (RR 1.07 (0.94-1.21)). Only N < 5 cases of each cancer (including cervix) were observed in the matched cohorts, precluding VE estimation.

Conclusions: HPV vaccination in women under 18 years old is associated with a substantial reduction in cervical cancer and pre-cancerous lesions, despite increased cervical screening in the vaccinated. Matching reduced confounding and other potential biases, but minimised sample size and precluded the analysis of VE against cancer. HPV vaccination reduced precancerous cervical lesions CIN2+ by 65% in the matched population, in line with previous systematic reviews of randomised controlled trials. Longer term data is needed to analyse the VE of HPV vaccination against related cancers.