NHS Digital Data Release Register - reformatted

London School of Hygiene and Tropical Medicine

Opt outs honoured: Y

Basis: Section 251 approval is in place for the flow of identifiable data

Format: Anonymised - ICO code compliant Non Sensitive

How often: One-Off

When: unknown — 11/2016

HSCIC Id: DARS-NIC-382718-N1T4C-v0.1

Data: Hospital Episode Statistics Admitted Patient Care

Data: Office for National Statistics Mortality Data

Data: MRIS - Cause of Death Report

Data: MRIS - Cohort Event Notification Report

Data: MRIS - Bespoke

Data: MRIS - Cause of Death Report

Data: MRIS - Cohort Event Notification Report

Data: MRIS - Scottish NHS / Registration

Data: MRIS - List Cleaning Report

Data: Office for National Statistics Mortality Data (linkable to HES)

Data: MRIS - Flagging Current Status Report

Output: Human papillomavirus (HPV) infection is known to cause cervical cancer, but it is a relatively common infection, especially in young women, which usually clears without any symptoms or long-lasting effects. There are different strains (known as genotypes) of HPV, and some are more likely to cause pre-cancer or cancer than others. Until recently, cervical cancer screening has been done using a smear test (known as cytology), but the latest scientific evidence points towards screening first for HPV infection (known as “HPV primary screening”). This method is currently being tested in six areas in England, and in January 2016, the UK National Screening Committee announced that primary HPV testing should be introduced countrywide. It is not sensible or cost-effective to refer a large number of women for treatment when their infection is likely to clear on its own, so women who are positive for HPV will be only referred if they also have some abnormal cells (from their cytology test). Cytology is not always the most efficient second test and screening studies such as the Manchester Cohort study can help policy makers decide what the best options are to save women being referred unnecessarily and to save money.

The long-term cervical cancer risk following HPV infection will be estimated from the following:

1. Long-term follow-up of women in The Manchester Study for whom HPV status was known at baseline,

2. a case-control analysis comparing baseline HPV status in those developing cervical cancer during follow-up in The Manchester Study.

The results (target 2017) will be presented at international HPV conferences including the International Papillomavirus Conference and the Eurogin conference on HPV held every 18 months respectively. The results will also be published in peer-reviewed journals such as the European Journal of Cancer and the British Journal of Cancer.

All outputs will be aggregate with small numbers supressed in line with HES analysis Guidance.

Activities: The request is for notification of and date of cancer incidence, mortality and current status (i.e. NHS, cancelled, emigration, armed forces etc.). In order to conduct a valid statistical analysis, it is essential to know the number of individuals at risk from developing the disease of interest at any point in time. This includes being aware of which members of the cohort are being actively followed at any point in time. Once an individual leaves the notification system, due to being cancelled or emigration for example, they must be excluded from the analysis. For example, any woman who emigrated would leave the study at this point and would not be able to re-enter the study because cervical cancer may occur while a women is living abroad.

LSHTM will send NHS Digital the following identifiers - NHS Number where known, Names (including former), DOB, Address, Postcode. This data will be from when the cohort was recruited.

NHS Digital will provide latest demographic data (NHS number and DOB only) , cancer, NHS exits/status and cause of death data. LSHTM will quality check and merged it with the current data held on the cohort. Before merging, fields containing names and addresses will be removed.

LSHTM data files being returned will not contain names or addresses, but will contain dates of birth and NHS numbers for linkage purposes to onward screening. LSHTM also hold cervical screening histories which include dates and results of cervical smears and associated histology results, and HPV results. LSHTM then analyse the data in terms of estimating risks of cervical cancer and CIN3 (cervical cancer-in-situ) associated with previous HPV results.

In addition to these “cohort analyses”, the team would like to retrieve stored, yet untested, samples from the Manchester Study from women who have subsequently developed cervical cancer or CIN3. A set of controls will be analysed as a nested case-control study within the cohort. The team can directly compare the screening histories and HPV results among those women who do and do not develop cervical cancer or CIN3.

Processing will include the following steps:
1. The Manchester cohort will be matched PDS (MIDAS)
2. NHS Digital will provide LSHTM with Cause of death and cancer registration data, NHS Number,DOB and NHS Exits.

The data will be processed at the LSHTM and will not be shared with any third parties. All outputs will be aggregate with small numbers supressed in line with HES analysis Guidance.

Objective: The objective for the Manchester Cohort is to study the long term risk of cervical cancer and cervical pre-cancer following Human papilloma virus (HPV) infection.

The aims are to obtain the data required to evaluate the long-term benefits and costs of alternative screening strategies using primary HPV testing and to investigate;

1. The long-term protection of a negative HPV test and hence the safe screening interval at different ages

2. Optimal ages at start and stopping screening

3. The role of HPV typing and test sensitivity

4. Triage of HPV positive women, particularly the interval to retesting for HPV positive women

The team will follow-up this unique cohort in order to determine long-term risks associated with HPV infection. HPV is the most common sexually transmitted disease but unfortunately most people do not know they are infected with the virus since the initial symptoms can be minor.

The cohort was recruited between 1987-1993 in collaboration with over 100 general practitioners and screening clinics in the Greater Manchester area who used the Christie Hospital cytology laboratory (now the Manchester Cytology Centre sited at Manchester Royal Infirmary). 78,062 cervical cell samples were collected from 61,564 women attending for routine screening. There was no age restriction. Participating practices and clinics covered a wide area in and around the city of Manchester, and offered screening either in the context of well-woman clinics or in association with family planning services.

The study was approved by the local ethics committee. Verbal informed consent obtained when the smear was taken was deemed appropriate at the time, as the clinical significance of HPV infection was not then known. However, verbal consent is not being presented as the legal basis for this application and is merely for background information. HPV assays were performed after recruitment had ended, and no HPV results were reported either to the cytology laboratory or to the women.

Samples taken before Jan 1989 were centrifuged and only the pellet was stored. This procedure (in the pre-PCR era) entailed some loss of DNA and the possibility of contamination. The proposed study will therefore be restricted to the 49,549 women recruited 1989-93.

The Manchester Study was an observational study and now LSHTM wish to 'flag' the cohort for cancer incidence and mortality and relate these outcomes back to their previous HPV results.

At the time the Manchester Cohort was set up, HPV testing was not routine or cheap and so the study team tested only a minority of samples. The untested samples were stored until such a time as funding could cover the testing costs. Once the Manchester cohort is flagged the study team will be able to see who has developed cervical cancer or cervical pre-cancer from the cancer registration data. LSTHM will then test the stored samples from these women and also a randomly selected control group to compare them.

In summary, the routine screening records collected on these women and the additional linked data will help inform policy makers about how best HPV testing should be done. Questions this research aims to influence are:

(1) Is it safe to leave a longer interval between screening tests when a woman has a negative HPV test?

(2) What follow-up tests should be done in women who test positive for HPV? We can evaluate cytology, genotyping (identifying the strain of HPV) or new testing methods.

(3) What age is it safe to stop screening? Can a woman stop screening if she has tested negative for HPV when aged 50 years?

Benefits: The demonstration that a high proportion of women who subsequently developed cervical cancer had detectable HPV by age 40, and often earlier, would be of major importance and may show for example, that a single HPV test in middle age may be the most effective practicable form of screening.

The London School of Hygiene and Tropical Medicine and the lead researcher in this area have been proactive in ensuring the health system and patients benefit from the results of this research. Indeed they have already influenced policy changes in this area, with the results from a similar study (ARTISTIC TRIAL). The results have influence the piloting of primary HPV screening. The LSHTM expect evidence from this cohort to influence further screening policy changes regarding screening interval and triage strategies.

This research will be disseminated officially in peer-reviewed papers. These will be used by the National Screening Committee to decide whether changes should be made to the screening programme. The lead in this research is also the chair of an advisory group specifically put together to advise the National Screening Committee on the scientific evidence that exists regarding cervical cancer and HPV screening and therefore this research could directly influence screening policy.

The London School of Hygiene and Tropical Medicine findings will add to the body of evidence to allow policy-makers to improve the cervical screening programme in the UK (and around the world)

Source: NHS Digital.