Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background 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\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 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

The recovery strategies to support cervical cancer elimination in lower-and middle-income countries (LMICs) following COVID-19 disruptions

The COVID-19 pandemic has exacerbated the existing challenges to achieving the WHO target of eliminating cervical cancer as a public health problem by working towards the target of fewer than four cases per 100 000 women. We reviewed the literature to identify potential recovery strategies to support cervical cancer prevention programs in lower-and middle-income countries (LMICs) following COVID-19 disruptions and the extent to which strategies have been implemented. Utilising the WHO health systems framework, we mapped these recovery strategies against the six building blocks to examine their reach across the health system. Most recovery strategies were focused on service delivery, while leadership and governance played a pivotal role in the continuity of cervical cancer prevention programs during the pandemic. Leadership and governance were the drivers for outcomes in the building blocks of health information systems, financing and critical support in operationalising service delivery strategies. In the aftermath of the COVID-19 pandemic with strained health resources and economies, stakeholders would significantly influence the coverage and sustainability of cervical cancer prevention programs. The support from multisectoral stakeholders would accelerate the recovery of cervical cancer prevention programs. To achieve the WHO target by 2030, we call for future studies to understand the barriers and facilitators from the perspectives of stakeholders in order to support the decision-making processes and information required to implement recovery strategies in LMICs

Flowchart outlining study design and recruitment.

<p>Flowchart outlining study design and recruitment.</p

Attitude towards vaccination and the HPV vaccine among 417 participants who were offered HPV vaccination between 2007 and 2009 as part of the National HPV Vaccination Program, living in Victoria, Australia, stratified by NHVPR confirmed vaccination status.

<p>Attitude towards vaccination and the HPV vaccine among 417 participants who were offered HPV vaccination between 2007 and 2009 as part of the National HPV Vaccination Program, living in Victoria, Australia, stratified by NHVPR confirmed vaccination status.</p

Demographic, lifestyle and sexual behaviour characteristics among 417 participants who were offered HPV vaccination between 2007 and 2009 as part of the National HPV Vaccination Program, living in Victoria, by NHVPR confirmed vaccination status.

<p>Demographic, lifestyle and sexual behaviour characteristics among 417 participants who were offered HPV vaccination between 2007 and 2009 as part of the National HPV Vaccination Program, living in Victoria, by NHVPR confirmed vaccination status.</p

HPV knowledge among 417 participants who were offered HPV vaccination between 2007 and 2009 as part of the National HPV Vaccination Program, living in Victoria, Australia, stratified by NHVPR confirmed vaccination status.

<p>Frequency of correct responses presented.</p

Factors associated with receipt of the HPV vaccine between 2007 and 2009 as part of the National HPV Vaccination Program among 417 female participants living in Victoria, Australia, overall and stratified by age-group at commencement of the HPV vaccination program.

<p>Factors associated with receipt of the HPV vaccine between 2007 and 2009 as part of the National HPV Vaccination Program among 417 female participants living in Victoria, Australia, overall and stratified by age-group at commencement of the HPV vaccination program.</p

Reported reasons for not receiving the HPV vaccine (A) and; measures to improve HPV vaccination rates (B) among unvaccinated female participants who were eligible for the HPV vaccine between 2007 and 2009 as part of the National HPV Vaccination Program.

<p>Reported reasons for not receiving the HPV vaccine (A) and; measures to improve HPV vaccination rates (B) among unvaccinated female participants who were eligible for the HPV vaccine between 2007 and 2009 as part of the National HPV Vaccination Program.</p

Routine cervical screening by primary HPV testing: early findings in the renewed National Cervical Screening Program

Objectives: To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV‐positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology‐ to primary HPV‐based screening. Design, participants: Retrospective cross‐sectional review of 195 606 specimens submitted for HPV testing, 1 December 2017 – 31 May 2018. Setting: Large community‐based general pathology laboratory in metropolitan Sydney. Main outcome measures: Prevalence of oncogenic HPV types (all, HPV16/18, non‐HPV16/18) by reason for HPV test (primary screening, non‐screening); for oncogenic HPV‐positive women in the age band recommended for primary HPV screening (25–74 years), prevalence of cytologic abnormality and rates of 12‐month follow‐up and colposcopy recommendations. Results: 195 606 samples were received: 157 700 (80.6%) for primary screening, 37 906 (19.4%) for non‐screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9–8.2%) and 20.9% of non‐screening tests (95% CI, 20.5–21.3%); 35.5% (95% CI, 34.7–36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18‐positive samples with high grade abnormality was 15.3% (95% CI, 14.2–16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8–6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3–5.5%) and direct colposcopy for 2.6% (95% CI, 2.5–2.7%) of screened women aged 25–74 years. Conclusions: High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology‐based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non‐screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round