THE LANCET: Cervical cancer rates reduced by 87% in women vaccinated against HPV, English study confirms

Peer-reviewed / Observational study / People

• Follow-up from the human papillomavirus (HPV) immunization programme using the bivalent vaccine Cervarix, which began in England in 2008, found that cervical cancer rates in women offered the vaccine between the ages of 12-13 were 87% lower than in an unvaccinated population.
• The study estimates that by June 2019, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of cervical carcinomas (pre-cancers) than expected in the vaccinated population in England.
• The study provides the first direct evidence of prevention of cervical cancer using a bivalent vaccine worldwide. 

Cervical cancer rates are 87% lower in women who were offered vaccination against human papillomavirus (HPV) when they were between the ages of 12-13 than in previous generations confirms a new study published in The Lancet.

The researchers also found reductions in cervical cancer rates of 62% in women offered vaccination between the ages of 14-16, and 34% in women aged of 16-18 when vaccination was introduced. This is the first direct evidence of prevention of cervical cancer using the bivalent vaccine, Cervarix.

HPV vaccination has been introduced in 100 countries as part of efforts by the World Health Organization (WHO) to eliminate cervical cancer. England initially used a bivalent vaccine which protects against the two most common types of HPV, responsible for approximately 70-80% of all cervical cancers. The English HPV vaccination programme was introduced in 2008, with vaccines given to women between 12-13 years old and “catch-up” vaccinations offered to older age groups up to the age of 18.

“Although previous studies have shown the usefulness of HPV vaccination in preventing HPV infection in England, direct evidence on cervical cancer prevention was limited,” says Professor Peter Sasieni, King’s College London, one of the authors of the paper “Early modelling studies suggested that the impact of the vaccination programme on cervical cancer rates would be substantial in women aged 20-29 by the end of 2019. Our new study aims to quantify this early impact. The observed impact is even greater than the models predicted.” [1]

The study looked at population-based cancer registry data between January 2006 and June 2019 for seven cohorts of women who were between the ages of 20-64 at the end of 2019. Three of these cohorts formed the vaccinated population, where women were vaccinated with Cervarix between the ages of 12-13, 14-16 and 16-18 respectively. Incidences of cervical cancer and non-invasive cervical carcinoma (CIN3) in the seven populations were recorded separately.

During the study period, 28,000 diagnoses of cervical cancer and 300,000 diagnoses of CIN3 were recorded in England. In the three vaccinated cohorts there were around 450 fewer cases of cervical cancers and 17,200 fewer cases of CIN3 than expected in a non-vaccinated population. The research found reductions in cervical cancer rates of 87% (with a confidence interval of 72-94%) in women targeted between the ages of 12-13 (89% of whom received at least one dose of the HPV vaccine and 85% of whom had received three jabs and were fully vaccinated), 62% (CI: 52-71%) in women potentially vaccinated between the ages of 14-16, and 34% (CI: 25-41%) in those eligible for vaccination between the ages of 16-18 (60% of whom received at least one dose and 45% of whom were fully vaccinated). The corresponding reductions in CIN3 rates were 97% in women vaccinated between the ages of 12-13, 75% in women vaccinated between the ages of 14-16 and 39% in women vaccinated between the ages of 16-18.

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts. As expected, vaccination against HPV was most effective in the cohorts vaccinated at ages 12-13 amongst whom the uptake was greatest and prior infection least likely,” says Dr Kate Soldan from the UK Health Security Agency and co-author [1]. “This represents an important step forwards in cervical cancer prevention. We hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated.”

Lucy Elliss-Brookes, Associate Director for Data Curation at NHS Digital and one of the authors of the paper said: “The findings of this study are hugely important in encouraging those eligible to take up the vaccine, but also in demonstrating the power of data [2] in helping medical researchers and the NHS to understand what causes cancer and how best to diagnose, prevent and treat it.” [1]

The authors acknowledge some limitations with the study, principally that cervical cancer diagnosis is rare in young women. In addition, the number of registered cases of cervical cancer is impacted by the age at which women are screened; most of the follow-up for women in vaccinated cohorts occurred under the age of 25 and small differences in the age of first screening can have a large impact on registered cervical cancer cases in women below this age. Because the vaccinated populations are still young, the authors stress that this means that it is still too early to assess the full impact of HPV immunisation on cervical cancer rates. However, it is important to note that the two most common HPV infections which the bivalent vaccine protects against are present in as many as 92% of women diagnosed with cervical cancer before the age of 30.

It should also be noted that the bivalent vaccine Cervarix used in the UK from 2008-2012. Since September 2012, the quadrivalent vaccine Gardasil has been used instead.

Writing in a linked comment, Professor Maggie Cruickshank from the University of Aberdeen (UK), who was not involved in the study, says: “The scale of HPV vaccination effect reported by this study should stimulate vaccination programmes in low and middle-income countries where the problem of cervical cancer is a far greater public health issue than those with well-established systems of vaccination and screening. The most important issue, besides the availability of the vaccine (related to the decision-makers in the health policy), is the education of the population to accept the vaccination, as an increase in the rate of immunization is a key element of success.”

NOTES TO EDITORS

This study was funded by Cancer Research UK. It was conducted by researchers from King’s College London.

[1] Quote direct from author and cannot be found in the text of the Article.
[2] Working from a statistical analysis plan, analysis code was written before the authors had access to the data. After testing on simulated data consisting of artificial cancer records, the code was sent to the National Cancer Registration and Analysis Service (NCRAS) for running on the real data and the results were shared. Patient data were not shared outside of NCRAS to maintain patient confidentiality.

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