HPV-Based Cervical Screening 'Could Save Lives'

Liam Davenport

February 07, 2019

Women who undergo cervical screening for high risk human papillomavirus (hrHPV) have more lesions detected at an earlier stage than those who have traditional liquid-based cytology (LBC) or 'smear' testing, which could lead not only to extended screening intervals but also more lives saved, say UK researchers.

Matejka Rebolj, senior epidemiologist, School of Cancer and Pharmaceutical Sciences, King's College London, UK, and colleagues studied data on more than 570,000 women in England who underwent cervical screening.

'Practicable On a Large Scale'

The research, which was published by The BMJ, showed that hrHPV detected  50% more cervical intraepithelial neoplasia (CIN) grade ≥2 than LBC testing, as well as 40% more CIN grade ≥3 and 30% more cervical cancer.

Importantly, a substantial proportion of CIN grade ≥2 lesions detected with hrHPV were in women who were negative on LBC testing.

The authors write that the study confirms that "primary hrHPV cervical screening is practicable on a large scale".

Moreover, the reduced incidence of CIN at follow-up screens with hrHPV compared to LBC testing supports "an extension of the screening intervals".

More importantly, the researchers believe that the change to hrHPV testing could lead to more lives being saved.

Speaking to Medscape News UK, Matejka Rebolj explained that, because the test can detect more pre-invasive lesions, more cancers will be prevented.

She said: "There is some glimpse of that in our very preliminary data that we are reporting in this paper, which is reassuringly following the results from earlier trials that had a much longer follow-up.

"We believe that what they saw in the follow-up, which is about a 70% decrease in interval cancers after a negative screening test, we will be able to see with the routine screening."

She said that this "should bring down the overall burden of cervical cancer by about 20%, and because you will be finding fewer cancers, fewer women will be dying from those cancers".

UK Cervical Screening Changes

In 2016, the UK National Screening Committee recommended that cervical screening be switched from LBC to hrHPV, and NHS England and Public Health England are undertaking a national rollout to be completed by the end of 2019.

In preparation for the rollout several screening laboratories have been partially converted to hrHPV, which has allowed its performance to be contemporaneously compared with that for LBC.

For the current study, the researchers gathered data from six partially converted screening laboratories, which cover approximately 13% of the Cervical Screening Programme in England.

The labs followed the nationally recommended protocol of screening women aged 25–64 every 3 years when aged <50 years, and every 5 years thereafter.

The women underwent routine screening with both hrHPV and LBC. Those who were hrHPV positive but LBC negative had an early recall at 12 months, and again at 24 months if they remained hrHPV positive.

The researchers included 578,547 women who were screened between May 2013 and December 2014 and followed up until May 2017.

Screening for hrHPV was performed in 183,970 (32%) women.

Colposcopies vs. LBC Screening

The researchers found that hrHPV testing plus early recall significantly increased the number of colposcopies performed versus LBC screening, at an adjusted odds ratio of 1.77.

CIN grade ≥2 was detected in 2.26% of women screened with hrHPV, while 1.37% had CIN grade ≥3 disease.

Crucially, approximately 1 in 4 of these lesions were detected after early recall of women who were HPV positive but LBC negative. 

The hrHPV testing protocol significantly increased the detection of CIN grade ≥2 over LBC testing, at an adjusted odds ratio of 1.49, as well as CIN grade ≥3, at an odds ratio of 1.44, and cervical cancer, at odds ratio of 1.27.

The researchers found that attendance for early recall was high, at 83% at 12 months, and attendance for rescreening was 76% at 24 months. Attendance for colposcopy remained high after early recall - 96% at 12 months, and 89% at 24 months.


Matejka Rebolj said that one advantage of the hrHPV test is that it allows women to self-sample.

This means that women who do not have the time to visit the GP or are too embarrassed to do so "will be able to take the sample themselves with a particular type of tester, which can then be tested for HPV in the laboratory".

Another factor associated with hrHPV testing that will have an impact on screening intervals in the coming years will be the ongoing effects of HPV vaccination.

She explained that increasing numbers of vaccinated women will become eligible for cervical screening, who "will be presenting with fewer infections and fewer lesions that will need treatment, and certainly fewer cancers".

"That means that there will not be as many positive tests, and there will be fewer women that will need to be told that they need diagnostics and treatment, which is going to be great."

She pointed out, however, that these women may not need to be screened every 5 years "but less frequently".

Matejka Ribolj concluded: "We don't exactly know what that is going to be, but that is certainly the expectation."

The research was supported by Public Health England (salary and laboratory activity) and Cancer Research UK. Public Health England had a role in designing the pilot, in the collection of the data, and commented on the manuscript.

Rebolj, and two other authors received financing from Public Health England (PHE) for the epidemiological evaluation. Rebolj attended meetings with various HPV assay manufacturers and received a fee for lecture from Hologic paid to employer. John Tidy received fees for lectures from Roche, Qiagen, and Hologic; conference registration, accommodation and travel from Sanofi Pasteur; consultancy fees and shareholder in Zilico; patent for electrical impedance spectroscopy in detection of cervical intraepithelial neoplasia with Zilico. Kay Ellis received fees for lectures from Beckton Dickinson and Roche and conference accommodation and travel from Hologic, Abbott, Becton Dickinson, and Roche. John Smith received personal speaker bureau fees from Beckton Dickinson and personal medical advisory board fees from Zilico. Thirteen authors received funding from PHE to support the NHS screening laboratory activity for the pilot. VF is employed by Norfolk and Norwich University Hospitals NHS Foundation Trust and received the speaker fees from Roche for conferences and travel and accommodation from Roche and Hologic for training and user group meetings. Alexandra Sargent received speaker fees from Roche, travel and accommodation from Roche for training, travel and accommodation from Abbott for a user group meeting, attended meetings with HPV assay manufacturers, and received kits for assay validation from Roche, Abbott, Hologic, Becton Dickinson, and Cepheid. Henry Kitchener is the Chair of the Advisory Committee for Cervical Screening (PHE).


BMJ 2019; 364: l240. doi: 10.1136/bmj.l240


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