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In this Double Take video from the New England Journal of Medicine, Dr. Julie Barzilay discusses the connection between certain strains of human papillomavirus (HPV) and cancer, as well as the evidence to support the safety and efficacy of the HPV vaccine in reducing the risk of cervical neoplasia. Strategies for discussing the HPV vaccine with patients and families are also reviewed.
Introduction: Despite the safety and efficacy of the human papillomavirus vaccine, thousands are impacted by human papillomavirus and its related cancers. Rural regions have disproportionately low rates of human papillomavirus vaccination. Primary care clinics play an important role in delivering the human papillomavirus vaccine. A positive deviance approach is used to identify workflows, organizational factors, and communication strategies in rural clinics with higher human papillomavirus vaccine up-to-date rates. Positive deviance is a process by which exceptional behaviors and strategies are identified to understand factors that enable success.
Methods: Rural primary care clinics were rank ordered by human papillomavirus vaccine up-to-date rates using 2018 Oregon Immunization Program data, then recruited via purposive sampling of clinics in the top and bottom quartiles. Two study team members conducted previsit interviews, intake surveys, and 2-day observation visits with 12 clinics and prepared detailed field notes. Data were collected October-December 2018 and analyzed using a thematic approach January-April 2019.
Results: Four themes distinguished rural clinics with higher human papillomavirus vaccine up-to-date rates from those with lower rates. First, they implemented standardized workflows to identify patients due for the vaccine and had vaccine administration protocols. Second, they designated and supported a vaccine champion. Third, clinical staff in higher performing sites were comfortable providing immunizations regardless of visit type. Finally, they used clear, persuasive language to recommend or educate parents and patients about the vaccine's importance.
Conclusions: Positive deviance identified characteristics associated with higher human papillomavirus vaccine up-to-date rates in rural primary care clinics. These findings provide guidance for rural clinics to inform human papillomavirus vaccination quality improvement interventions.
More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.
METHODS:
In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.
FINDINGS:
We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+. After 5-8 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0·17, 95% CI 0·11-0·25) among girls aged 13-19 years, and decreased significantly by 66% (RR 0·34, 95% CI 0·23-0·49) among women aged 20-24 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0·46, 95% CI 0·33-0·66) among girls aged 13-19 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0·33, 95% CI 0·24-0·46) among girls aged 15-19 years, decreased significantly by 54% (RR 0·46, 95% CI 0.36-0.60) among women aged 20-24 years, and decreased significantly by 31% (RR 0·69, 95% CI 0·53-0·89) among women aged 25-29 years. Among boys aged 15-19 years anogenital wart diagnoses decreased significantly by 48% (RR 0·52, 95% CI 0·37-0·75) and among men aged 20-24 years they decreased significantly by 32% (RR 0·68, 95% CI 0·47-0·98). After 5-9 years of vaccination, CIN2+ decreased significantly by 51% (RR 0·49, 95% CI 0·42-0·58) among screened girls aged 15-19 years and decreased significantly by 31% (RR 0·69, 95% CI 0·57-0·84) among women aged 20-24 years.
INTERPRETATION:
This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects.
FUNDING:
WHO, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé.
