Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study

Abstract

Objective: To quantify the effect on cervical disease at age 20 years of immunisation with bivalent human papillomavirus (HPV) vaccine at age 12-13 years.

Design: Retrospective population study, 1988-96.

Setting: National vaccination and cervical screening programmes in Scotland.

Participants: 138 692 women born between 1 January 1988 and 5 June 1996 and who had a smear test result recorded at age 20.

Main outcome measures: Effect of vaccination on cytology results and associated histological diagnoses from first year of screening (while aged 20), calculated using logistic regression.

Results: 138 692 records were retrieved. Compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 showed an 89% reduction (95% confidence interval 81% to 94%) in prevalent cervical intraepithelial neoplasia (CIN) grade 3 or worse (from 0.59% (0.48% to 0.71%) to 0.06% (0.04% to 0.11%)), an 88% reduction (83% to 92%) in CIN grade 2 or worse (from 1.44% (1.28% to 1.63%) to 0.17% (0.12% to 0.24%)), and a 79% reduction (69% to 86%) in CIN grade 1 (from 0.69% (0.58% to 0.63%) to 0.15% (0.10% to 0.21%)). Younger age at immunisation was associated with increasing vaccine effectiveness: 86% (75% to 92%) for CIN grade 3 or worse for women vaccinated at age 12-13 compared with 51% (28% to 66%) for women vaccinated at age 17. Evidence of herd protection against high grade cervical disease was found in unvaccinated girls in the 1995 and 1996 cohorts.

Conclusions: Routine vaccination of girls aged 12-13 years with the bivalent HPV vaccine in Scotland has led to a dramatic reduction in preinvasive cervical disease. Evidence of clinically relevant herd protection is apparent in unvaccinated women. These data are consistent with the reduced prevalence of high risk HPV in Scotland. The bivalent vaccine is confirmed as being highly effective vaccine and should greatly reduce the incidence of cervical cancer. The findings will need to be considered by cervical cancer prevention programmes worldwide.

Fig 1

Schedule of immunisation, screening, and data collection. Only a few birth years in the 1990s were eligible. Girls born in 1994 not covered in first year of catch-up and immunised either side of 15th birthday, depending on date of birth. For first invitation to screening at age 20, women born in 1996 only eligible if date of birth was before 6 June. Data collated for all screening related events in first year of screening. Women born in 1996 had at least 15 months between initial invitation to screening and data extraction

Fig 2

Cytological abnormality (% of women screened) by year of birth and immunisation status. 1988-90=pre-immunisation programme cohort; 1991-94=catch-up cohort; 1995-96=routinely immunised cohort. Whiskers represent 95% confidence intervals. ASCUS=atypical squamous cells of undetermined significance; LSIL=low grade squamous intraepithelial lesion; HSIL=high grade squamous intraepithelial lesion (HSIL-M=mild dyskaryosis; HSIL-S+=severe dyskaryosis)

Fig 3

Histological abnormality (% of women screened) by year of birth and immunisation status. Whiskers represent 95% confidence intervals. CIN=cervical intraepithelial neoplasia; 1988-90=pre-immunisation programme cohort; 1991-94=catch-up cohort; 1995-96=routinely immunised cohort