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Understanding CervicalCheck laboratory quality assurance

By Fiona Murphy, Chief Executive, National Screening Services

How do I feel reassured about screening laboratories used in CervicalCheck?

In Dr Gabriel Scally’s new Implementation Review Report, he reports that CervicalCheck, the national cervical screening programme, has an “excellent system of Quality Assurance (QA) for laboratory service provision in place”. I am pleased to see this endorsement of our QA processes. As the Chief Executive of the National Screening Service, I need to be sure that the laboratories that we commission are safe and of high quality. 

I’m not a laboratory expert so how do I do that? For me, it’s about the 4 P model – purpose, processes, performance and people. I need to be sure we know what we are trying to achieve, that our processes are clear and safe, that we measure our performance and that we have the right people with the right expertise doing the work and overseeing the results. I’ll explain a bit more, but some background facts first.

Screening tests

The purpose of cancer screening tests is to detect pre-cancer or early-stage cancer in asymptomatic people so that timely diagnosis and early treatment can be offered, where this treatment can lead to better outcomes for some people. Screening invites people in a target population who do not have symptoms (asymptomatic) to undergo testing. Under international screening criteria, the test should be simple, safe, precise, validated and acceptable to the population.

An ideal cancer screening test would perfectly separate people who have cancer from those who do not. In real life, however, screening tests cannot do this – they can only suggest the likelihood that a person is at risk of cancer.

Even with the best technology, there will always be people whose cancer is not detected by the screening test (false-negative result) and people who do not have cancer but are given an abnormal result (false-positive result).

The cervical screening test

The test used up to 2020 in Ireland was cytology where medical scientists (called cytoscreeners in many countries) look at cells from the cervix on a slide to spot any abnormalities. A pathologist (doctor) then reviews all abnormalities. While this technology was the best available for decades, detection rates in the best programmes internationally were limited to 75% of abnormalities. We were amongst the first countries to move to HPV screening in 2020.

Sensitivity is the ability of the screening test to identify early cancer changes in affected people (abnormal result). Laboratories that provide cytology screening find about 15 in every 20 abnormalities, but they will not find 5 in 20. This can be because the slide did not contain abnormalities (even though the women may have them) or the scientists did not identify them on the slide. The new HPV test is better and will find 18 in every 20 abnormalities but will still not find 2 out of 20.

Specificity is the ability of the screening test to identify people without cancer as negative (normal result). Again, cytology as a screening test was okay at this and about 90% accurate but it meant that 10% of women who were told they had an abnormality actually didn’t and had to go for colposcopy for further investigation.

The choice of screening test is based on evidence review and technology assessments (by bodies such as HIQA) and usually agreed internationally. Cytology was the accepted test worldwide, but now many countries are moving over to the HPV test as the first test also.

The laboratories

The type of laboratory used to test for cervical screening is a cytology laboratory – part of a pathology laboratory in a hospital or an independent facility. All need to have accreditation by an independent inspection body (In Ireland that is Irish National Accreditation Board) and have the expert staff and structures to process thousands of tests. They all use international quality standards to ensure their processes are safe and of high quality. Screening laboratories may be subject to extra standards and inspections because they are providing national programmes for invited otherwise well people.

So what do we do to reassure ourselves (and others) about our laboratories?

Purpose

Screening is a population health measure, which uses a simple test, which is sufficiently accurate to use to reduce the rate of cancer and death in the population. In contrast, when people have symptoms which may be caused by cancer, more invasive and more complex tests are justified to find out what is wrong, with a much greater level of accuracy. These more accurate diagnostic tests could not be used for screening as they are more invasive, associated with more risk, and even if the resources were available to provide these tests in large numbers, they would not be acceptable to people with no symptoms.

Because of this and because we are inviting people who are otherwise well to come for a test, screening needs to have rigorous standards. These are set out internationally for all countries to follow and we have experts in Ireland to set the specific standards and measurement against these.

Quality Assurance (QA) is the process of checking that standards are met and encouraging continuous improvement. Assuring and driving up the quality of services is essential if population screening is to achieve the intended benefits to population health, while minimising unintended harms to those taking part. This benefit-to-harm ratio is especially important given that screening programmes are designed for populations or individuals who do not have any symptoms of the disease in question.

All screening programmes regularly measure themselves against these standards to make sure we are meeting our agreed purpose e.g. to reduce the rate of cancer or detect it early.

Processes

It is important for me to understand how the screening test is actually tested in a lab.

  • All slides are reviewed initially by a medical scientist - this will be a medical scientist who has had additional training to review cytology slides. 
  • All negative and inadequate samples are rescreened by a second scientist so every slide is looked at twice to reduce the risk of missing an abnormality
  • If either screener sees an abnormality, this is then passed to a pathologist (A medically trained doctor) to review further.

Changes in cells are not always clear cut. It is straightforward to see the difference between normal healthy calls and abnormal cells, however there is a whole spectrum of changes in between. The changes which the medical scientists and doctors are looking for may be very subtle, and may only be present in a small number of cells on the slide. Sometimes abnormal cells are simply not present on the slide, or so subtle that mild changes are not classed as abnormal. Occasionally, changes may also be missed. 

I understand that this is both inevitable and normal across the world. When the decision to start a screening programme was first made, this was clear in the evidence review – it would never be 100% accurate. But laboratories try to attain the highest accuracy possible.

Laboratories monitor detections of abnormalities by scientists/screeners, and by pathologists. The statistics for individuals are then compared to the lab as a whole and to expected national rates. If anyone falls outside the expected rates, they are supported with additional training. 

Quality assurance in the laboratory is a combination of internal quality control (IQC) and external quality assessment (EQA) e.g. through accreditation or peer review and applied to the entire sample pathway.

Quality control measures apply to each analytical test in the laboratory, and encompass the entire process beginning with sample collection up to final reporting. Examples of IQC measures include:

  • Addition of verified standard manufacturer control samples e.g. HPV positive and negative samples in each run
  • Repeating analyses for consistency 
  • Statistical control charts to check for trends in test results
  • QC screen of cytology samples by a second screener, often referred to as QC review

Performance

The laboratories review each individual scientist regularly and their laboratory as a whole. On top of that, the labs report these figures to the CervicalCheck QA team who also monitor them monthly.  

The published detection rates of low- and high-grade abnormalities in CervicalCheck are in line with international norms. In a cervical screening programme, the expected proportion of low-grade and high-grade abnormalities in the populations is 3-8% and 0.7-1.3% respectively and CervicalCheck has consistently met these standards for many years.

There are other important measures, such as the positive predictive value. This is the percentage of people with an abnormal smear, who have cancer (that is, the percentage of abnormal results which are true positives). The programme also checks that positive screen tests are checked against subsequent histology test to see how accurate the screen test was.

We measure this to ensure the programme is picking up the right level of cancer in the population. This gives reassurance that the labs are finding as many cancers as you would expect.

We also measure a range of other aspects e.g.

  • Are the actual number of tests being taken in Ireland equal to the numbers predicted?
  • How quickly will women get their results?
  • Are samples getting to the lab on time, how quickly are the samples being processed in the lab?
  • Are the expected number of women being referred to Colposcopy and how quickly are they getting there if they need it?

Every year CervicalCheck publishes the programme statistics and checks to see how they compare with the evidence from research and from practice in other countries.

It is my view that the more information we share with people about how we work and how we perform, the better. Over the last 2 years we have committed to being open and transparent in all aspects of our work – we regularly tell people how we are doing, we report consistently to the HSE, the Department of Health, and to the public on our website; we tell people when we get things wrong and we work hard to fix these for the future.

People

There are 2 aspects to this – do we have well qualified people working in the laboratories and do we have the right level of expertise overseeing this and giving me (and the public) reassurance?

Both the medical scientists and doctors who work in the laboratories are highly trained people, regulated by CORU and the Medical Council (or equivalent professional regulators in other countries), bound by their own professional code of practice but also by the quality assurance standards set by CervicalCheck. This ensures that only qualified and suitable professionals report on our tests.

An experienced medical scientists/cytoscreener/cytotechnologist will undertake a minimum of 2 years in cytology (involving the supervised screening of training slides), followed by success at the appropriate examination relevant to the laboratory concerned e.g. the NHS CSP Certificate of Competence in Cervical Cytology for the UK and Ireland, or graduation from a nationally approved School of Cytotechnology and possess certification by the American Society of Clinical Pathology (ASCP). 

Consultant pathologists in Ireland and the UK will have taken the FRCPath examination and usually sit the Certificate of Higher Cervical Cytopathology Training (CHCCT) Examination. In the US, consultant pathologists will be anatomic pathology (AP) board-certified. All staff will undergo an induction programme and be subject to training and assessment prior to sign-off of competency by departmental training officers. All staff competencies and workload volumes are reviewed on a regular basis and updated to ensure they remain highly competent.

In terms of oversight, a Clinical Advisory Group (CAG) comprising national and international experts advises the CervicalCheck senior management team on clinical pathways and protocols. The CervicalCheck team works closely with service providers (Primary care, cytology and histology laboratories and colposcopy units) through their relevant advisory leads and CervicalCheck staff.

The Cervical Screening Quality Assurance Committee monitor standards for each part of the cervical screening programme as are set out in Standards for Quality Assurance in Cervical Screening for: 

  • Programme operations
  • Primary care and other settings
  • Laboratories providing HPV testing, cytology, and histopathology services
  • Colposcopy

In addition, CervicalCheck now has a Laboratory Advisory Group (LAG) with members drawn from the Laboratory Clinical Advisor, Laboratory Quality Coordinators, internal and external clinical specialists including representatives of the RCPI Faculty of Pathology, ACSLM, scientific and technical expert advisors and a representative from the NSS Quality, Safety and Risk Management team. They work to monitor, maintain and improve upon minimum standards of service, performance and quality across the laboratory elements of the CervicalCheck screening programme.

A QA team from the cervical screening programme also visits laboratories directly to make sure that they are adhering to these standards. The QA laboratory team has been significantly enhanced with additional expertise. The team has undertaken visits to both laboratories used by CervicalCheck in 2021 and approved them both to continue providing a service. The team report back to the LAG above to make sure that all are satisfied with the findings. In addition, the QA visit reports are reviewed by the externally chaired CervicalCheck Quality assurance committee. This is chaired by an international public health screening expert and also has international and national expert members.

What about errors?

Cancer screening will not find all cancers. Cancers may not be present or detectable when the screening test is performed. It is really important for all screening participants to be aware that they should see their GP if they develop symptoms, and should not wait until their next screen. Screening is a process to reduce cancer risk in people with no symptoms – people with symptoms need to enter a different, diagnostic pathway. The occurrence of an interval cancer in a previously screened individual is anticipated in all screening programmes worldwide and is both a statistical certainty and a personal disaster for the women affected.

Most interval cancers will arise with nothing on previous screens or because of the inherent limitations of the tests used to detect them e.g. that cytology can only find 15 in 20 abnormalities. False reassurance is an acknowledged harm of screening. In a very small number of cases, false negatives will occur due to human error, which can be minimised but never eliminated from a subjective test. This is one of the reasons women are encouraged to go for screening regularly so that there are multiple chances to pick up any abnormalities over the years when she is most at risk. However the importance of seeing your GP if symptoms arise, regardless of screening results, cannot be overstated.

It is inevitable that errors will occur but what is important it how we deal with them. The processes described above are all used to reduce the chance of errors e.g. double screening, regular checking of competence, accreditation and quality assurance etc. When error does happen, it is important that women can get answers to any questions they might have. 

The Interval Cancer Reports, issued in October 2020 by the Expert Reference Groups, outline a new and comprehensive approach to interval cancer evaluation in people who have been screened by Ireland’s cancer screening programmes. The NSS Interval Cancer project groups brought together experts from screening services, symptomatic services, healthcare policy, ethics, communications, the legal profession, and patient/public advocates to begin planning, design and implementation. Work continues to develop the best approach to the management of cytology reviews and categorization of review findings. Planning, development and evaluation of a patient requested review process involving an initial cohort of requests is currently in progress for CervicalCheck.

So am I reassured and can you be?

Yes, I believe that the processes in place in laboratories is good and has limited the number of false positive and false negative results to the lowest it can be. The processes in CervicalCheck QA are now much improved so that we can provide documented reassurance of the labs and the right experts are in place to review findings and advise on the safety and quality of our laboratories. Ireland has a fantastic cervical screening service and we should all be proud of the impact it has had to save many women’s lives.

Fiona Murphy
Chief Executive

National Screening Service
Nov 2022


 

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