Matejka Rebolj, PhD King’s College London, London, UK

HPV Testing for Primary Cervical Cancer Screening Interview with:

Matejka Rebolj, PhD King’s College London, London, UK

Dr. Rebolj

Matejka Rebolj, PhD
King’s College London, London, UK

Henry Kitchener, MD FRCOG FRCS University of Manchester, Manchester, UK

Dr. Kitchener


Professor Henry Kitchener, MD FRCOG FRCS
University of Manchester, Manchester, UK What is the background for this study?

Response: We now have reliable and affordable technologies to detect human papillomavirus (HPV), a virus which is universally accepted as the cause of cervical cancer. Various large trials confirmed that cervical screening could be improved by replacing the smear (cytology) test that has been in use for decades, with HPV testing. Many countries are now making the switch. In England, this is planned for the end of 2019. To test how to run HPV testing within the English National Health Service, a pilot was initiated in 2013 in six screening laboratories. We also wanted to determine whether the encouraging findings from the trials could be translated to everyday practice. This is important not only because we will be using different HPV tests, but also because women undergoing screening in trials are much more selected than those who are invited to population-based screening. What are the main findings?

Response: The pilot includes more than 1.5 million women, of which about a third were screened for HPV. Here, the new way of analysing the sample in a laboratory identified about 50% more women who have high-grade cervical intraepithelial neoplasia (CIN2+); these are the women in whom treatment is recommended in order to halt the progression to cancer. This benefit was seen across the entire screening age range, which is set at 25-64 years in England. This initial surge in CIN2+ diagnoses was followed by an approximately 70% lower detection when women aged less than 50 underwent a routine recall in 3 years. This means that receiving a negative HPV test can better predict longitudinal absence of cervical lesions than smear tests. Because of this, women will not need to be screened as often.

HPV infections are, however, frequent and many of them will never lead to cervical cancer. This is why the pilot operated a triage strategy, whereby only those infected women were referred for a diagnostic colposcopy whose samples also showed abnormal cells. If there were no abnormal cells, women were invited to at most two early recalls in 12-month intervals.

During this time, about 40% of HPV positive women cleared their infections without any intervention. Unlike in the trials where the adherence tended to be poor, more than 4 out of 5 women in the pilot adhered to repeated testing in the early recalls. This high adherence to early recalls proved crucial to achieving the uplift in the detection of CIN2+. Early recalls were also instrumental in reducing the number of women sent for colposcopy to about half of those who were HPV positive, although the number who needed a colposcopy was still about 80% higher than with smear tests. What role does the HPV vaccine play in these findings? 

Response: The data we have from the pilot do not yet include birth cohorts offered HPV vaccination at age 12-13 years. These women, of whom more than 80% were vaccinated, will start being invited to screening from 2020 onward. Given the high effectiveness of this vaccine against the two most oncogenic genotypes, we expect a substantial effect on the screening outcomes. The most important effect will be that of a lower proportion with HPV infections, and a lower proportion with abnormal cells and CIN2+ lesions. Hence, fewer will need to undergo a colposcopy. As most colposcopies are typically undertaken in young unvaccinated women, we believe that vaccination will reduce the pressure on additional colposcopy services. What should readers take away from your report?

Response: The pilot showed that HPV testing is practicable in the NHS screening laboratories, without pushback from the women undergoing screening or the primary care staff. Despite protocol violations that can be expected in everyday “real world” practice, the results of HPV testing were impressive. This suggests that the national roll-out should be smooth. What recommendations do you have for future research as a result of this work?

Response: This is the first report from the pilot and the data continue to be collected and analysed. We will use those data to provide additional evidence on various aspects of the screening process, such as the use of infection genotyping for triage to colposcopy, the need for early recalls in women who are discharged from the programme when they reach age 65 years, and the effect of the vaccine on the screening processes and disease detection. We will also continue monitoring the safety of HPV testing at longer routine intervals. Is there anything else you would like to add?

Response: For the women, the procedure of taking an HPV screening sample will be identical to that of the smear test. They will be, however, informed of the presence of this sexually transmitted infection, and will be more likely to be recommended for additional testing. It is important to understand women’s reactions to these changes so that the programme learns what are their needs in terms of information, support, communication. This is being monitored as part of the pilot, and the results will be reported shortly.

Any disclosures?

All disclosures of potential conflicts of interest were declared in the online version of the paper.


Primary cervical screening with high risk human papillomavirus testing: observational study

BMJ 2019; 364 doi: (Published 06 February 2019) Cite this as: BMJ 2019;364:l240

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Last Updated on February 13, 2019 by Marie Benz MD FAAD