Measuring vaccine effectiveness against persistent HPV infections: a comparison of different statistical approaches.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is endorsed by the World Health Organization as an intermediate endpoint for evaluating HPV vaccine effectiveness/efficacy. There are different approaches to estimate the vaccine effectiveness/efficacy against persistent HPV infections. METHODS: We performed a systematic literature search in Pubmed to identify statistical approaches that have been used to estimate the vaccine effectiveness/efficacy against persistent HPV infections. We applied these methods to data of a longitudinal observational study to assess their performance and compare the obtained vaccine effectiveness (VE) estimates. RESULTS: Our literature search identified four approaches: the conditional exact test for comparing two independent Poisson rates using a binomial distribution, Generalized Estimating Equations for Poisson regression, Prentice Williams and Peterson total time (PWP-TT) and Cox proportional hazards regression. These approaches differ regarding underlying assumptions and provide different effect measures. However, they provided similar effectiveness estimates against HPV16/18 and HPV31/33/45 persistent infections in a cohort of young women eligible for routine HPV vaccination (range VE 93.7-95.1% and 60.4-67.7%, respectively) and seemed robust to violations of underlying assumptions. CONCLUSIONS: As the rate of subsequent infections increased in our observational cohort, we recommend PWP-TT as the optimal approach to estimate the vaccine effectiveness against persistent HPV infections in young women. Confirmation of our findings should be undertaken by applying these methods after longer follow-up in our study, as well as in different populations.

High Effectiveness of the Bivalent Human Papillomavirus (HPV) Vaccine Against Incident and Persistent HPV Infections up to 6 Years After Vaccination in Young Dutch Women.

Background: Monitoring vaccine effectiveness (VE) in vaccination programs is of importance for assessing the impact of immunization. This study aimed to estimate the VE of the bivalent human papillomavirus (HPV) vaccine against incident and 12-month persistent infections up to 6 years after vaccination. Methods: In 2009-2010, girls eligible for the vaccination catch-up campaign (ie, those aged 14-16 years) were enrolled into a prospective cohort. Annually, participants completed a questionnaire and submitted a self-collected vaginal swab sample for HPV testing by the SPF10-LiPA25 assay. We compared sociodemographic characteristics and infection rates between vaccinated and unvaccinated girls. The VE was adjusted for characteristics related to HPV vaccination status. We used combined end points for VE estimation. Results: In total, 1635 women, of whom 54% were fully vaccinated, were included for VE estimation. The adjusted VE against HPV16 and 18 persistent infections amounted to 97.7% (95% confidence interval [CI], 83.5%-99.7%). We found a VE against HPV31, 33, and 45 persistent infections of 61.8% (95% CI, 16.7%-82.5%). We found no indications that the protection against vaccine or cross-protective types changes over time. Conclusion: Our findings of nearly full protection against vaccine-type persistent infections and significant cross-protection to nonvaccine types in a population-based cohort study confirm the effectiveness of the bivalent HPV vaccine as estimated in trials. We found no indications for waning protection up to 6 years after vaccination.

Ethnic and regional differences in STI clinic use: a Dutch epidemiological study using aggregated STI clinic data combined with population numbers.

OBJECTIVES: Ethnic minorities (EM) from STI-endemic countries are at increased risk to acquire an STI. The objectives of this study were to investigate the difference in STI clinic consultation and positivity rates between ethnic groups, and compare findings between Dutch cities. METHODS: Aggregated population numbers from 2011 to 2013 of 15-44 year-old citizens of Amsterdam, Rotterdam, The Hague and Utrecht extracted from the population register (N=3 129 941 person-years) were combined with aggregated STI clinic consultation data in these cities from the national STI surveillance database (N=113 536). Using negative binomial regression analyses (adjusted for age and gender), we compared STI consultation and positivity rates between ethnic groups and cities. RESULTS: Compared with ethnic Dutch (consultation rate: 40.3/1000 person-years), EM from Eastern Europe, Sub-Sahara Africa, Suriname, the Netherlands Antilles/Aruba and Latin America had higher consultation rates (range relative risk (RR): 1.27-2.26), whereas EM from Turkey, North Africa, Asia and Western countries had lower consultation rates (range RR: 0.29-0.82). Of the consultations among ethnic Dutch, 12.2% was STI positive. Positivity rates were higher among all EM groups (range RR: 1.14-1.81). Consultation rates were highest in Amsterdam and lowest in Utrecht independent of ethnic background (range RR Amsterdam vs Utrecht: 4.30-10.30). Positivity rates differed less between cities. CONCLUSIONS: There were substantial differences in STI clinic use between ethnic groups and cities in the Netherlands. Although higher positivity rates among EM suggest that these high-risk individuals reach STI clinics, it remains unknown whether their reach is optimal. Special attention should be given to EM with comparatively low consultation rates.