HPV Vaccine Linked to 'Dramatic' Decrease in Cervical Disease

Peter Russell

April 04, 2019

Routine vaccination of girls aged 12 to 13 with the human papillomavirus (HPV) vaccine was strongly associated with a "dramatic" reduction in pre-invasive cervical disease in later life, an observational study found.

The research, published in The BMJ , also found a reduction in disease among unvaccinated women, which the researchers said could be a result of 'herd protection'.

Scotland has an established national cervical screening programme. In 2008, it introduced a national HPV immunisation programme for girls aged 12 and 13, with a catch-up programme for girls up to 18 years.

Lead author Prof Tim Palmer, honorary senior lecturer in the Division of Pathology at the University of Edinburgh, said a high vaccine uptake of 85% to 90% among 13-year-olds in the 1995 birth cohort, contributed to the strength of the results. "Scotland has some of the best data there is in the world," he told Medscape News UK, "but we've also got the ability to link things together between data sources."

He added: "Whatever effect the vaccine has, we're going to show it best because we've got about the highest vaccine uptake in the world."

Analysis of Vaccination and Screening Records

Researchers used this data to measure the impact of routine vaccination of girls with the bivalent HPV vaccine, targeting HPV types 16 and 18, on levels of cervical intraepithelial neoplasia (CIN), which is divided into grades 1, 2+, or 3+ according to the risk of developing invasive cancer.

They analysed vaccination and screening records for 138,692 women born between 1st January 1988 and 5th June 1996 who had a screening test result recorded when they were aged 20.

The data included:

  • Unvaccinated women born between 1988 and 1990, who were first screened between 2008 and 2010

  • Women born between 1991 and 1994 who were eligible for the catch-up vaccination programme when they were aged 14 to 17 years and who were first screened between 2011 and 2014

  • Women born between 1995 and 1996 who were routinely vaccinated at the age of 12 to 13 years and first screened between 2015 and 2016

Measuring Vaccine Effectiveness

Compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 showed an 89% reduction in CIN grade 3 or worse, the researchers found.

Furthermore, there was an 88% reduction in CIN grade 2 or worse, and a 79% reduction in CIN grade 1.

The analysis showed that vaccination at a younger age increased its effectiveness. So, vaccine effectiveness was 86% for CIN grade 3 or worse for women vaccinated at age 12 to 13 compared with 51% for women vaccinated when they were aged 17 years.

"What we see in the catch-up cohort is a lesser effect than we see in the routine cohort," said Prof Palmer, who is clinical lead for cervical screening in Scotland. "That's a measure of partly lower uptake, and partly the fact that some of them have been exposed to HPV already."

Evidence of Herd Protection

Unvaccinated women also showed a reduction in disease, suggesting that these women had benefited from herd protection, the researchers said.

Among the unvaccinated 1995-96 cohort, herd protection reduced the risk of CIN grade 1 by 63%, grade 2 by 67%, and grade 3 by 100% compared with unvaccinated women in 1988-90.

"For HPV to continue to be there, it's got to pass from one person to the next," said Prof Palmer, "and it goes from boy to girl and girl to boy; and if you break that chain then you stop transmission – it no longer propagates through the community."

The researchers point to some limitations. For example, only 51% of vaccinated women in the study attended cervical screening at the age of 20 (23% for unvaccinated women) which they say could have led to over-estimation of vaccine effectiveness.

"We know that there's herd immunity because the unvaccinated girls that did turn up had less disease, so the herd protection is a given," said Prof Palmer. "Which means that even the girls that don't turn up are probably going to be at lower risk of disease."

Results 'Are Dramatic'

In a linked editorial, Julia Brotherton, medical director at VCS Foundation in Australia, described the findings as "dramatic", while also highlighting the value of integrated registries "that can systematically collect and use high-quality data from screening and vaccination programmes".

She added: "We must work towards a world in which all girls and their families are offered, and the majority accept, HPV vaccination, wherever they live."

Prof Palmer emphasised: "One of the things this study really does hammer home is that the anti-vaccine lobby are actually peddling falsehoods."

Commenting on the study, Robert Music, chief executive of Jo's Cervical Cancer Trust, said: "The findings of this research are highly exciting and clearly demonstrate the impact of the HPV vaccine in protecting the cervical health of future generations.

"We are lucky to have such an effective prevention programme which means the elimination of cervical cancer is firmly on the horizon.

"Focusing on communities and areas where take up is below the national average should be a priority."

BMJ 2019;365:l1161

Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study, Palmer T et al. Paper.

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