Screening for cervical cancer

Full version in Danish: Screening for livmoderhalskræft

Summary

Cervical cancer arises from the cells lining the cervix and the mouth of the womb. The disease may occur at any age, including in younger women. In Denmark there are nearly 400 new cases and approximately 100 cervical cancer deaths every year. At least 99 % of cervical cancer cases are caused by infection with human papillomavirus (HPV) in that persistent HPV infection may lead to the development of cell abnormalities, some of which may develop into cervical cancer. Many countries have introduced screening programmes with the intention of identifying and treating the more severe cases of cell abnormalities to prevent them from developing into cervical cancer. HPV infection may furthermore be prevented by vaccination. The available HPV vaccines protect against the HPV types that cause 70-90 % of all cervical cancer cases.

In Denmark, cervical cancer screening was introduced in a number of municipalities and counties in the 1960s. Since 2007, the Danish Health Authority has published national recommendations for cervical cancer screening, and today a national screening programme is covering women between 23 and 64 years of age. The recommendations were last updated in 2012, and new knowledge has since become available on the use of HPV testing as the primary screening test. Several countries are considering or have already decided to introduce HPV testing into their screening programmes. One of the aims of updating the current recommendations has therefore been to review the evidence base for the use of HPV tests in cervical cancer screening and to assess whether HPV testing should be recommended as the primary screening test in Denmark. Based on a systematic review of the available evidence, the Danish Health Authority assessed that both cytology and HPV screening are efficient methods to prevent cervical cancer. HPV screening is likely to prevent more cases of cervical cancer, but probably at the cost of more women being referred for further assessment of or treatment for cell abnormalities that would not have caused cancer. Based on the available evidence, it has not been possible to quantify benefits and harms of HPV vs. cytology screening in a Danish screening context. Nor has it been possible to determine which screening programme design that achieves the best balance between beneficial and harmful effects, e.g. how HPV positive screening tests should be further tested to avoid referral of too many women for further assessment and/or treatment. The Danish Health Authority therefore recommends that both of the testing methods are made available in the screening programme, and that they are rolled out in the regions in a way that enables the monitoring of the beneficial and harmful effects of both cytology and HPV screening. These recommendations appear in Chapter 7 along with recommendations for quality assurance of both screening methods.

Another aim has been to update the recommendations with new initiatives to ensure that women who wish to participate in the screening programme are given the possibility to attend. 25 % of women do not attend screening, and these women account for almost half of all cervical cancer cases. Participation in the screening programme should be based on an informed choice of the woman, however evidence shows that non-attendance is not always the result of a deliberate decision to opt out of screening. Therefore, recommendations regarding information material for women (Chapter 9) as well as initiatives for ensuring participation (Chapter 11) are included in the new recommendations.

In order to support the implementation of the screening programme and to ensure national coordination and consistency, it is recommended that a National Steering Group for Cervical Cancer Screening is established under the regions (Chapter 8). The monitoring of the screening programme, that is already undertaken by the Danish Quality Database for Cervical Cancer Screening (DKLS) should continue. The DKLS steering group should work in joint collaboration with the newly established National Steering Group for Cervical Cancer Screening to assess whether any of the current monitoring indicators need to be replaced or if new indicators are needed (Chapter 10).

Ethical aspects of cervical cancer screening are also explored (Chapter 13), as are the expected resource implications of the proposed revisions to the programme (Chapter 12). The final chapter highlights several aspects, such as future demographic changes and scientific developments that may necessitate further updates to the screening programme, including the incidence of cervical cancer among older women and screening of HPV vaccinated women (Chapter 14).

1.2 Overview of recommendations

The recommendations are described in detail in the individual chapters and summarised below.

Recommendations for testing methods (Chapter 7):

Current recommendations (1) from 2012 that are maintained in the new recommendations:

• Primary screening with cytology testing should be performed with liquid-based technique rather than the conventional smear test, and the test result should be reported according to the Bethesda classification.
• Women aged 23-29 years should be offered cervical cytology testing every three years according to the current guidelines.
• Women aged 60-64 years should be offered HPV testing as in the current programme.
• It is recommended that every region has an internal system that monitors inadequate samples and provides feedback to doctors with many inadequate samples.

New recommendations:

• The National Steering Group for Cervical Cancer Screening is to coordinate an overall national plan for a controlled, differentiated implementation of HPV screening among women aged 30-59 years to enable a comparison of cytology and HPV screening in a Danish context.
• Differentiation and comparison of the two screening methods are to take place both at the national level and within each region.
• The National Steering Group for Cervical Cancer Screening must prepare screening algorithms for cytology screening of women aged 23-29 years and women aged 30-59 years, respectively.
• The National Steering Group for Cervical Cancer Screening should prepare a screening algorithm for HPV screening of women aged 30-59 years. This should include triage with cytology on all positive HPV tests and additional triage if the cytology examination shows low grade cell abnormalities (ASCUS or LSIL).
• It is recommended that the National Steering Group for Cervical Cancer Screening lays down national guidelines on the quality assurance of both cytology tests and HPV tests, also including an assessment of the minimum number of cytology and HPV tests to be performed.
• The National Steering Group for Cervical Cancer Screening should investigate how to best maintain competences and quality assurance within cytology examination in the future.
• The National Steering Group for Cervical Cancer Screening must define which quality requirements should apply to HPV tests eligible for use in the Danish cervical cancer screening programme.

Recommendations for organisation (Chapter 8):

• It is recommended that the Danish Regions establishes a National Steering Group for Cervical Cancer Screening, to which regional and specialist members are appointed. The Groups main task is to ensure a consistent and coordinated implementation of the Danish Health Authority’s national recommendations for the cervical cancer screening programme across all regions.
• The National Steering Group for Cervical Cancer Screening should engage relevant and wide-ranging specialist expertise to carry out its tasks, for example through the establishment of ad hoc specialist committees to address specific issues.
• It is recommended that each region should launch initiatives that ensure that all women are offered the possibility to attend screening. This should also be a focus point of the National Steering Group for Cervical Cancer Screening.
• It is recommended that the National Steering Group for Cervical Cancer Screening ensures the availability of a national template for audit of new cases of cervical cancer and to extend the audit to cover also women older than 70 years.
• Invitation to screening, organisation of sample collection and communication of results should remain unchanged. All pathology departments/screening secretariats should send a copy of the results of the screening tests taken at the general practitioner (GP) directly to the woman herself, provided that the woman has given her consent.
• The second reminder for cervical cancer screening should include an offer for self-sampling to test for high-risk HPV infection. The National Steering Group for Cervical Cancer Screening should develop templates for information, invitation and test result letters to be used in this regard.
• In case of a missing follow-up test on inadequate or abnormal test results, it is recommended that pathology departments send reminders to the sampling doctor and possibly to the woman herself.

Recommendations for information material (Chapter 9)

• It is recommended that all regions send out identical invitation and test result letters based on templates prepared by the National Steering Group for Cervical Cancer Screening.
• The invitation letters must be sent by digital post and should include links to information material on the website of the Danish Health Authority.
• The invitation letter should summarise the information material and advise where to find further information.
• The Danish Health Authority should prepare information material for publication on the website of the Danish Health Authority.
• It is recommended that test results and follow-up recommendations are sent both to the sampling doctor and to the woman directly from the screening secretariat/pathology department in case of samples taken at the GP.
• It is recommended that the National Steering Group for Cervical Cancer Screening prepares national templates for self-sampling offers, including invitation, information and test result letter.

Recommendations for monitoring (Chapter 10):

• The monitoring of the screening programme should continue to be undertaken by DKLS, and DKLS should continue to publish annual reports in the same format as previously.
• The annual reports should include comments on the results of the individual indicators from the DKLS steering group. The National Steering Group for Cervical Cancer Screening and DKLS steering group should continue to assess if there is reason to replace or add indicators.
• It is recommended that DKLS, in collaboration with the National Steering Group for Cervical Cancer Screening, considers introducing supplementary indicators to contribute to the quality assurance of the use of HPV testing.
• The National Steering Group for Cervical Cancer Screening should establish supplementary indicators for the differentiated implementation of HPV screening, to be monitored by DKLS and included in the DKLS annual reports.
• It is recommended that the national follow-up on the monitoring is organised under the National Steering Group for Cervical Cancer Screening, which collaborates with the regional operators on the quality assurance of the programme.

Recommendations for participation (Chapter 11):

The Danish Health Authority recommends that a number of initiatives are launched over the coming years to increase participation in the screening programme:

• Every region should offer the possibility of self-sampling to women who have neither opted out nor gone for their test after receiving the invitation and the first reminder letter. The invitation and information material should be prepared by the National Steering Group for Cervical Cancer Screening. Participation and follow-up on HPV positive test results after self-sampling should be monitored, e.g. by DKLS including an indicator thereon in its annual report.
• Initiatives should be considered in GP practices, such as the possibility of choosing the gender of the examiner, after hours screening without an appointment, possibly on a rotational basis between the doctors in the area.
• All regions should launch initiatives that can facilitate access for women who want to participate, such as mobile clinics.
• It is recommended that the individual regions as well as the National Steering Group for Cervical Cancer Screening carry out further investigations and take measures to identify and address the barriers characteristic of the groups with the lowest participation rates.
• It is recommended that the information material and invitation letters are translated into several languages.
• Information letters and information material should inform the recipients about the possibility of opting out of the programme and how to opt back in.
• It is recommended that the National Steering Group for Cervical Cancer Screening should work to establish practical decision-making tools for opting in or opting out of the cervical cancer screening programme that interested women can use.
• It is recommended to launch population-targeted or campaign-based initiatives to raise awareness of the cervical cancer screening programme.