Introduction of HPV testing in England
The NHS Cervical Screening Programme for England announced that from April 2011 HPV testing would be incorporated into the programme. This followed the publication of the NHS Operating Framework 2011/2012 Document from the Department of Health. Roll out of HPV testing as HPV testing to triage women who have their first cytology sample showing borderline nuclear changes or low grade dyskaryosis and HPV test of cure at six months for newly treated women with negative, borderline or low grade dyskaryosis has been completed with test of cure extended to all women treated for CIN with negative, borderline or low grade in 2013. Those women who are positive for high risk HPV DNA in either the triage group or test of cure, including women with negative cytology in the test of cure group, are referred for further colposcopy. All women who are negative for high risk HPV DNA, including women with borderline changes or low grade, are discharged back to routine screening. Selection of the HPV testing platform has been a local decision and varies across England.
Northern Ireland, Scotland and Wales
Plans for introduction of HPV testing have been reviewed in Northern Ireland, Scotland and Wales. Northern Ireland have adopted the same roles of HPV testing in triage and test of cure as England. Cervical Screening Wales has introduced HPV testing after treatment as Test of Cure and will make a recommendation to the Welsh assembly government on any potential plans to adopt HPV triage as a policy. The Cervical Screening Programme in Scotland started HPV testing as a test of cure in 2012. Women treated for CIN 1/2/3 are followed up in primary care and have co-testing by cytology and high risk HPV at 6 months. Women with dyskaryosis and/or positive high risk HPV are referred back to colposcopy. An HPV reference group reviewed the potential implementation of further HPV testing within the Scottish Cervical Screening Programme and a business case is now being developed for primary HPV screening in preference to triage.
Rationale for HPV testing
The aetiological relationship between the high risk oncotypes of the human papillomavirus (HPV) and cervical cancer means that the presence of high risk HPV in the cervix increases risk of CIN and its absence implies virtually no risk at that time. HPV testing can be clinically useful for risk assessment either in managing borderline cytology results or in predicting risk of treatment failure, and even as a primary cervical screening test in place of cytology.
HPV testing is made far more feasible by liquid based cytology and testing for HPV has become possible on a mass scale with the advent of quality assured kit tests, such as Digene Hybrid Capture 2 , Roche Cobas 4800, Abbot rtHPV, Genprobe HPV Aptima and Hologic Cervista HPV. All of these tests can provide a generic positive or negative result based on a 'cocktail' of probes against the relevant high risk types detected in cervical cancer.
These tests are very sensitive, which of course reduces their specificity and particularly in young women limits their usefulness in screening. Due to the particular importance of type 16 as well as type 18, 31, 45 and 52 for example, there is considerable interest in HPV genotyping which will add specificity to the result. An HPV-16 positive result has a higher likelihood of being associated with a high risk lesion than type 51 for example. A number of newer tests have been developed and results from clinical practice are being evaluated.
Impact of HPV testing on colposcopy
The introduction of HPV triage did not impact on referral rates to colposcopy depending on local practice for the management of women with borderline nuclear changes or mild dyskaryosis. Those colposcopy services which saw women with borderline changes only after the third abnormal smear or who only saw women after two mildly dyskaryotic smears had the largest increase in referrals. Clinics who saw patients after one mildly dyskaryotic smear had a less significant increase. This increase was temporary and clinics now see less new referrals than previously.
Both the pilot and sentinel site studies demonstrated there are significant variations between cytology laboratories. To maximise the advantage of HPV triage it will be important to practice a more conservative approach to the management of women referred with these abnormalities. Women who are referred and found to have CIN I on punch biopsy would probably benefit from annual follow up rather than a more frequent clinic attendance. Women with normal colposcopy can be discharged back to routine cervical screening, therefore avoiding any unnecessary follow up. There have been 2 UK publications confirming the low risk of CIN3+ in women with normal colposcopy returned to routine recall.
HPV Primary Screening
As far as HPV testing in primary screening is concerned, the results of a number of European and Finnish trials will be helpful in determining exactly how best to design a HPV based programme, and whether it could replace cytology as the primary test. The emerging results of clinical trials indicate that HPV testing is more sensitive than cytology and it could be used effectively in primary screening in women aged over 30 years. There are very high positive rates for HPV testing in younger women with a low positive predictive value which limits the clinical effectiveness of primary HPV screening under the age of 30. This may be more useful in the HPV immunised women as we should no longer see high rates of positive rates with the marked reduction of HPV16/18.
Data from the UK primary HPV screening trial, ARTISTIC, indicates that a negative HPV test provides the same degree of ‘protection’ over 2 screening rounds as negative cytology for one screening round. This suggests that with primary HPV screening, screening rounds may be extended.
The NHSCSP has established a Primary HPV study group with a remit to investigate the role of primary HPV screening with reflex cytology. New clinical algorithm’s pertaining to screening and referral to colposcopy has been developed and evaluated at selected laboratories and associated colposcopy clinics. This primary HPV study started in April 2013 with first invitations. Women with abnormal cytology will be referred for colposcopy and those with normal cytology will be rescreened after 12 months. At colposcopy, women with biopsy confirmed CIN1 will be discharged back to the community and re-tested at 12 months by HPV. A recent update on the NHS CSP has the most recent update on primary screening in England.