US expands HPV vaccine recommendations

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VaccineIn new human papillomavirus (HPV) vaccine developments, a US federal advisory group has expanded recommendations to include men through age 26 and some older adults, and a large meta-analysis with data on 60m people from 14 countries found that the vaccine has substantially cut infections and precancerous lesions.

The Advisory Committee on Immunisation Practices (ACIP), an outside expert group that advises the US Centres for Disease Control and Prevention (CDC), unanimously voted to recommend expanding HPV vaccination for men through age 26. The earlier recommendation for teen boys and young men went through age 21. Also, ACIP voted 10 to 4 to recommend that adults ages 27 through 45 who had not been adequately vaccinated to talk to their doctors about being vaccinated. The vaccine is not licensed for adults older than 45.

The American College of Obstetricians and Gynaecologists (ACOG) applauded ACIP’s expanded recommendations. Dr Christopher Zahn, ACOG’s vice president of practice activities, said: “Today’s decision from ACIP emphasises what the data has shown – that the HPV vaccine is safe and effective for use in patients ages 27 to 45, and that use of the vaccine in this age group should be the result of shared decision-making between patients and their trusted physicians.”

He added that though the vaccine is safe and effective in patients ages 27 to 45, the target age that offers the greatest benefit from the vaccine is ages 11 to 12 years old. And Zahn said ACIP’s action should encourage doctors to routinely discuss the vaccine with their adult patients.

The CDC’s earlier HPV recommendations haven’t changed. To prevent HPV-linked cancers of the cervix, vagina, anus, head, or neck, the agency has recommended routine HPV vaccination for girls and boys at age 11 or 12 and for other young people who weren’t vaccinated earlier. But the CDC routinely adopts ACIP’s recommendations.

Meanwhile, the meta-analysis by researchers from Canada‘s Laval University is an update to its 2015 review. Aside from 18 studies covered in the earlier report, the new analysis includes 47 newer ones published between February 2014 and October 2018 that examined the frequency of one more HPV endpoint before and after the HPV vaccine was introduced to the population.

The 65 studies are from 14 high-income countries and incorporate data from 60m people over 8 years. Of the studies the team examined, 23 measured the vaccine’s impact on HPV infection, 29 evaluated the impact on anogenital warts, and 13 looked at precancerous lesions.

The group’s earlier meta-analysis showed substantial decreases for the two types – HPV 16 and HPV 18 – that cause the majority of cervical cancers and anogenital warts in vaccinated women, with herd effects for boys and older women. The earlier study wasn’t able to assess precancerous lesions, because it was too soon after vaccination to gauge any possible impact.

In its latest findings, the team found that HPV 16 and HPV 18 decreased 83% in girls ages 13 to 19 and 66% in women ages 20 to 24 after 5 to 8 years of vaccination. They also saw a 54% reduction in three other HPV types (31, 33, and 45) in girls age 13 to 19.

Use of the vaccine also significantly reduced anogenital wart diagnoses in girls and women from ages 15 to 29 and in boys and men ages 15 to 24.

Precancerous lesions decreased significantly 5 to 9 years following vaccination: 51% in screened girls ages 15 to 19 and 31% in screened women ages 20 to 24.

Countries with multi-cohort vaccination and high HPV vaccine coverage saw greater and faster impacts, along with herd effects.

Dr Mélanie Drolet, at the Centre de recherche du CHU de Québec – Université Laval, Québec, the study’s first author, said: “Our results provide strong evidence that HPV vaccination works to prevent cervical cancer in real-world settings as both HPV infections that cause most cervical cancers and precancerous cervical lesions are decreasing.”

The authors said the results reinforce the recent World Health Organisation (WHO) recommendation that countries introducing the vaccine should include multiple age cohorts of girls ages 9 to 14 years old, rather than a single cohort.

Another of the study co-authors, Dr Marc Brisson, at the Santé des Populations et Pratiques Optimales en Santé, Hôpital Saint-Sacrement, Centre de recherche du CHU de Québec – Université Laval, said the HPV landscape is rapidly changing, with several countries changing their dose schedules and including both genders, with the availability of a newer vaccine that covers more HPV types.

“It will be crucial to continue monitoring the population-level impact of HPV vaccination to examine the full effect of these changes in strategies and quantify the effect of vaccination in low-income and middle-income countries,” he said.

In a related commentary, Dr Silvia de Sanjose, with the non-profit health group PATH in Seattle, and Dr Sinead Delany-Moretlwe, with the University of  the Witwatersrand in Johannesburg, South Africa, wrote that the new study findings can help health officials focus on priority targets with the vaccine and re-evaluate their current policies, especially given the global call to eliminate cervical cancer.

Settling on the optimal number of age cohorts for vaccination could yield budget and programme benefits, as multiple cohorts would need fewer vaccine doses, they wrote.

“The authors emphasise the importance of redoubling our efforts to tackle the fiscal, supply, and programmatic barriers that currently limit HPV vaccine programmes,” Sanjose and Delany-Moretlwe wrote. “With these efforts, HPV vaccination could become a hallmark investment of cancer prevention in the 21st century.”

Abstract
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 5–8 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.

Authors
Mélanie Drolet, Élodie Bénard, Norma Pérez, Marc Brisson

CIDRAP material
The Lancet abstract
The Lancet commentary


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