Background

Despite HPV vaccines, screening will remain central for decades to control cervical cancer. Recently, HPV testing alone or with cytology was introduced as an alternative to cytology screening. However, most HPV infections are harmless and additional tests are required to identify women with progressing infections or precancer. With three options for primary screening, and without clear strategies for triage of screen-positive women, there is great confusion about the best approach. Also, increasing HPV vaccination coverage will lead to lower disease prevalence, and force new screening approaches. Currently recommended triage strategies for primary HPV screening include HPV genotyping for HPV16 and HPV18 and cytology. Other alternatives that are currently evaluated include p16/Ki-67 dual stain cytology, host methylation, and viral methylation testing. Clinical management of women with cervical cancer screening results is moving to use risk thresholds rather than individual test results. Specific risk thresholds have been defined for return to primary screening, repeat testing, referral to colposcopy, and immediate treatment. Choice of test algorithms is based on comparison of absolute risk estimates from triage tests with established clinical thresholds. Importantly, triage tests need to be evaluated together with the primary screening test and the downstream clinical management. An optimal integrated screening and triage strategy should reassure the vast majority of women that they are at very low risk of cervical cancer, send the women at highest risk to colposcopy at the right time, when disease can be colposcopically detected, and minimize the intermediate risk group that requires continued surveillance.

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.

Background:In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.Methods:We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20–21 in 2008–2012.Results:By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women.Conclusions:To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.

Prevalence was reduced, and early evidence indicates herd immunity.