BACKGROUND: Based on immunogenicity studies, a 2 dose HPV vaccination-schedule was recently recommended for girls younger than 15 years. We aimed to investigate the effectiveness of quadrivalent HPV (qHPV) vaccination against CIN2 or worse (CIN2+), by age at vaccination, number of doses, and to test whether optimal timing of 2 doses of qHPV vaccine can confer the same level of protection as the originally recommended three dose-schedule.

METHODS: A population-based cohort of all women aged 13-30 years, living in Denmark or Sweden during 2006-2013, was followed for qHPV vaccination status and first occurrence of CIN2+.

RESULTS: The study cohort comprised 2,253,561 women, of which 33% were vaccinated during follow-up, and 1.7% were diagnosed with CIN2+. Vaccination at ages 13-16 and 17-19 was associated with a reduced risk of CIN2+ after 3 doses (IRR = 0.23, 95% CI 0.11-0.49, and IRR = 0.65, 95% CI 0.41-1.03, respectively), compared to being unvaccinated. After 1 and 2 doses there was a reduced risk, but not statistically significant. Women vaccinated ages 13-16 with 2 doses, where time between first and second dose was 5 months or longer showed no difference in risk compared to 3 doses.

CONCLUSIONS: Women vaccinated with 3 doses of qHPV showed a reduced risk of CIN2+ if they were vaccinated before age 20, with a further reduced risk if vaccinated before age 17. Vaccination with 2 doses, with the second dose 5 months or longer after the first dose, did not yield an increased risk of CIN2+, compared to 3 doses.