Reducing the cervical cancer burden

Cervical cancer continues to represent a significant health problem in Ireland. It is the ninth most commonly diagnosed cancer in women, with in excess of 260 new cases per year, and is the 12th most common cause of cancer death in women with up to 70 deaths per year. Up to 2010, Irish cervical cancer rates had been increasing year on year and today still remain higher than most western European countries. Since 2010 there has been a reversal of these trends with the latest report from the National Cancer Registry Ireland (NCRI) showing a reduction in the numbers of new cancers as well as improvements in survival from established cervical cancers. These trends are likely to be a direct result of improved cervical cancer prevention measures implemented in recent years.

The knowledge that cervical cancers are preceded by a relatively long precancerous phase, cervical intraepithelial neoplasia (CIN) and adenocarcinoma <em>in situ</em> (AIS), forms the basis for organised cervical screening programmes, which aim to identify women with these changes who can then be treated before invasive cancer develops. Key components of successful screening programmes include high levels of population coverage (80 per cent and over) as well as timely access to quality assured diagnostic and treatment facilities.

This year CervicalCheck, the National Cervical Screening Programme, will mark 10 completed years of providing free testing through primary care settings to the approximate 1.1 million women aged 25-60 years in Ireland.

Liquid-based cytology (LBC) to detect cellular (cytological) abnormalities is used as the primary screening test and an average of 1,250 smear (cytology) tests are performed daily as part of the programme. These are delivered by over 4,000 smear takers, mainly based in primary care. Helping women and healthcare professionals to track when the next test is due is a web-based tool at www.cervicalcheck.ie  – Ireland is the only screening programme in the world that has such a feature.

<h3><strong>Screening targets</strong></h3>

It is an ambition of CervicalCheck that more than 80 per cent of women in the target population have been screened within five years. The latest five-year coverage is 79.7 per cent. Since the beginning of CervicalCheck, younger women have been more likely to participate (84.4 per cent of women aged 25-29 years have been screened compared to only 69.6 per cent of women in the 55-59 year old group), although coverage of the older age groups continues to improve as the programme matures. This year, as part of the Cerviva research consortium, CervicalCheck will explore the attitudes and knowledge of screening among older women to inform screening promotion within these groups. In addition, coverage varies geographically across the country – in the latest annual report published in September 2017, it was noted that eight counties had achieved the target of 80 per cent with one of those counties achieving higher than 90 per cent. Disappointingly, five counties still appeared with coverage below 75 per cent (<strong>Figure 1</strong>).

<h3><strong>Colposcopy</strong></h3>

Access to timely diagnosis and treatment is crucial for successful cervical screening programmes.

Fifteen colposcopy services across the country provide quality-assured diagnosis and treatment with dedicated multidisciplinary teams. The number of women attending colposcopy increased significantly in the first eight years of the CervicalCheck programme with a peak of 17,909 new patients attending for the first time in the eighth year of the programme.

Long waiting times were a feature of colposcopy services before the introduction of CervicalCheck. The waiting times for colposcopy have decreased, reaching the standard of 90 per cent less than two weeks for suspected cancer, 90 per cent within four weeks for suspected adenocarcinoma <em>in situ,</em> and 90 per cent within eight weeks for low-grade referrals. Increased capacity in colposcopy has delivered significant improvements in waiting times. Since the fifth year of the programme the waiting times have met national standards for all categories of smear test abnormalities.

The number of treatments performed annually has also increased since the start of the CervicalCheck programme and currently more than 7,000 women undergo treatment annually. More than 95 per cent of treatments are performed as outpatients under local anaesthetic. Avoiding overtreatment is of particular relevance because of the potential adverse effect of repeated treatments on future pregnancies. Tailoring excisional treatments to the clinical finding as well as the increased use of ablative treatments in a quality-assured fashion minimise potential harms.

A key objective of a cervical screening programme is the detection of high-grade CIN and the yield of these abnormalities is one of the hallmarks of success. To date, more than 51,000 cases of high-grade pre-cancer and 1,300 cancers have been detected. While this is encouraging and has already resulted in a reduction in the numbers of cervical cancers, it is important to recognise that cervical screening programmes cannot prevent all cervical cancer cases. Cervical screening tests should not be regarded as diagnostic tests and are never 100 per cent accurate. False negative test results lead to potentially missed opportunities to detect and treat precancerous abnormalities. Cervical cancer may develop in the time between a negative screening test and a woman’s next screening (interval cancer). False positive test results can result in unnecessary colposcopy with increased anxiety for women. Screening programmes need to balance these risks in a trade-off between early effective treatment and avoiding harms related to screening.

<h3><strong>HPV</strong></h3>

The discovery that more than 99 per cent of cervical cancers arise from a persistent infection with certain types of the human papillomavirus (HPV) provides new opportunities for cervical cancer prevention. The most obvious example of this is the school-based HPV vaccination programme, which has been in place since 2009 and has the potential with screening to make cervical cancer a rare disease for future generations of Irish women. For the women who make up the current screening population, there is the possibility to enhance the effectiveness of screening by using tests that check for HPV infection by one or more of 14 HPV types associated with cervical cancer. 

For the last five years, CervicalCheck colposcopy services have been using a combination of cytology and HPV testing to allow a more accurate definition of the risk of high-grade CIN. This has been useful both following treatment as well as in the management of women who have not yet been treated. Women with results categorised as low risk are eligible for discharge from colposcopy and a return to routine screening. This avoids multiple follow-up visits and unnecessary testing with more effective use of resources as well as reducing unnecessary anxiety for women. 

In 2015, CervicalCheck introduced reflex HPV testing to triage women with low-grade abnormalities, a policy designed to enhance the early diagnosis and treatment of high-grade CIN. When low-grade cytological abnormalities are detected, the programme laboratories test the sample for infections with certain types of HPV. The additional information provided by this test is used to plan the next step in the programme for these women.

Without adjunctive HPV testing, these women were managed with repeat smear tests at shorter intervals with referral to colposcopy only if these changes persisted. The need for multiple repeat tests can be worrying and inconvenient for women and can be associated with a lack of compliance and the risk of default. There is also the possibility of a delay in the diagnosis and treatment of women who have high-grade CIN/AIS or indeed the tiny minority of women who have early cancerous changes.

The use of a test for high-risk HPV infections provides real-time information and reassurance for women who have a very low risk of cancer, reducing the need for repeat smear tests and the possibility of default. While a positive HPV test results in more women having to have a colposcopy, it allows earlier recognition of high grade CIN/AIS, which can then be treated promptly and effectively. The results of this policy for the first full year of operation year (September 2015-August 2016) were published in the last CervicalCheck annual report. Of the 15,046 women with low-grade changes who had HPV triage, 8,062 (53.4 per cent) were referred to colposcopy earlier due to HPV triage while 6,984 (46.4 per cent) were recommended as routine. During this year, the highest number of high-grade abnormalities at colposcopy was recorded since the beginning of the programme, highlighting the earlier detection.

By reducing the threshold for referral to colposcopy there is a need to focus on the management of the larger proportion of women who have no CIN detected. While the emphasis is on reassurance for these women, in practice some of these women would traditionally have had multiple follow-up visits before being discharged to community surveillance.  A change to a policy of more rapid discharge has been informed by new evidence from the UK, which confirms that women without evident CIN who have a satisfactory colposcopy can be safely discharged from colposcopy and advised to have a repeat smear test in the community in three years.

<h3><strong>HPV versus cytology</strong></h3>

Based on the overall positive experience with HPV testing as part of CervicalCheck, the question arises as to whether it is time to consider changing the order of the primary screening tests. Instead of the majority of women having a cytology test and only a minority being tested for HPV infection – should this be reversed? Should screening for HPV be the primary test with only a minority of women having a reflex cytology test? To inform this decision the National Screening Service (NSS) asked HIQA to carry out a health technology assessment (HTA) on the use of tests for HPV infection as part of CervicalCheck. The report was published in May 2017 and recommended replacing cytology with testing for HPV as the primary test. Changing to this strategy would have the advantage of preventing more cancers while reducing the number of screens a woman has in her lifetime. The report found that these changes would benefit women by making the screening process more clinically effective as well as reducing unnecessary tests for most women with longer intervals between tests. In addition, older women who may have been less well screened could be included in the screening programme. Testing for the HPV virus will also be a more appropriate strategy for the cohort of women who have received the vaccination against HPV.

This recommendation to switch from primary cytology screening to primary HPV screening is in keeping with developments in other high-income countries. Australia, Italy, Netherlands, New Zealand, Sweden and the UK have all recommended the implementation of primary HPV screening. In January 2017, the Netherlands was the first country with an organised cervical screening programme to fully transition from primary cytology screening to primary HPV screening at five-yearly intervals for women aged 30 to 60 years. The screening interval is extended to 10-yearly for HPV-negative women aged at least 40 years. Australia plans to transition to five-yearly primary HPV screening for women between the ages of 25 and 69 years from January 2018. New Zealand plans to transition to this strategy later in 2018.

<h3><strong>Conclusion</strong></h3>

Much has been achieved in the last 10 years in cervical cancer prevention in Ireland. The challenge is to build on these achievements and sustain the momentum. CervicalCheck has commenced an ambitious implementation programme to plan and deliver this major change. This will need to incorporate elements such as IT and laboratory configuration as well as the development of dedicated communication, educational and training tools. With the first group of women who have been vaccinated against HPV due to celebrate their 25th birthday in 2018 and enter the cervical screening programme, this change should enable the continued reduction of cancer incidence and mortality from cervical cancer for Irish women into the future.

<strong>References on request</strong>