The Role of Early Detection and Treatment of Anal Intraepithelial Neoplasia in the Prevention of Anal Squamous Cell Carcinoma in Women: Establishing the Disease Burden in Women with Genital Cancer

Imperial College London (ICL) requires access to NHS England National Disease Registration Service (NDRS) Cancer Registration data for the following research project:

The Role of Early Detection and Treatment of Anal Intraepithelial Neoplasia in the Prevention of Anal Squamous Cell Carcinoma in Women: Establishing the Disease Burden in Women with Genital Cancer

The following is a summary of the aims of the research project:

Women are the population most affected by anal cancer, but also the population most neglected with respect to anal cancer prevention strategies. As a result, women often miss their window for early diagnosis and intervention, instead, they often present later and with advanced disease. Given its rarity, screening the entire female population for anal cancer would be impractical. With that said, targeting high-risk sub-groups, such as women with genital cancers is likely desirable.

Current evidence has identified a clear relationship between genital High-Grade Squamous Intraepithelial Lesions (HSIL) and/or Squamous Cell Carcinoma (SCC) and anal HSIL and/or SCC, with these genital pathologies representing a significant risk factor for anal cancer in women. However, research in this area is still lacking; with significant variation between studies in respect to the prevalence of anal HSIL and/or SCC in those that have previously been diagnosed with genital HSIL and/or SCC.

This study aims to clarify how many women in England with anal cancer or HSIL have also been diagnosed with genital HSIL and/or cancer and will explore the effects of specific sociodemographic risk factors on the incidence of synchronous anal and genital pathology and forms part of a PhD thesis; this will help determine which patients are likely to benefit from closer anogenital surveillance. Furthermore, this study aims to add to a body of research that can be used to develop guidelines and services that are targeted at the early detection and treatment of anal cancer in women.

In support of this purpose ICL request access to the following NDRS Datasets:

- NDRS Cancer Registry Data: The receipt of this data is necessary for understanding how individuals with a diagnosis of anal HSIL and/or SCC, who have also had a previous diagnosis of genital HSIL and/or SCC, present, the stage of their disease at presentation, the recurrence of their disease, treatments received, their ethnicity and sociodemographic status.

This information will allow the study team to 1. Determine the number of women with anal HSIL and/or SCC who have also been previously diagnosed with genital HSIL and/or SCC; and 2. Understand which patient populations may be at the highest risk.

The level of data will be pseudonymised.

The data will be minimised as follows:

Data will be limited to a study cohort identified by the NDRS as meeting the following criteria:

- Women in England aged over 25 years diagnosed with anal cancer and/or HSIL between 2001 and 2020 who also have a vulval and/or vaginal and/or cervical cancer and/or HSIL diagnosis within the 20-year period before or 1-year period after their anal cancer/HSIL diagnosis, respectively.

- This means the earliest vulval and/or vaginal and/or cervical cancer and/or HSIL diagnosis will be in 1981 and the latest in 2020.

Imperial College London is the research sponsor and the data controller and is responsible for ensuring that the data will only be processed for the purposes described above. The term of the 3 year agreement is required because this data request forms part a PhD thesis. ICL require access to the dataset until the end of Feb 2026 to allow for any corrections or amendments to be made.

The lawful basis for processing personal data under the UK General Data Protection Regulation (GDPR) is:

Article 6(1)(e)- processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the data controller.

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j)- processing is necessary for archiving research purposes in the public interest in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and interests of the data subjects.

This research is deemed in the public interest as it has not yet been established how many women with anal precancer/cancer have also been affected by genital precancer/cancer and this project aims to finally answer this question. By establishing the size of this high-risk population in England this has the potential to influence genital cancer guidelines to include anal cancer awareness and target high risk groups for closer anogenital surveillance, potentially resulting in earlier diagnosis and more favourable outcomes.

The funding is provided by Red Trouser Day (https://redtrouserday.com/), a charity that raises money to support colorectal cancer research. Red Trouser Day has not helped influence the scope of the study nor will they have the ability to influence the outcomes or suppress any of the findings of the research.

In line with the National data opt-out policy, opt-outs are not applied because the data bring disseminated under this agreement is not Confidential Patient Information as defined in section 251(10) and (11) of the National Health Service Act 2006

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

No data will flow into NHS England for the purposes of this Agreement.

The NHS England NDRS will provide the relevant records from the NDRS Cancer Registry to Imperial College London. The data will contain no direct identifying items. The data will be pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

Once the data has been securely uploaded to the ICL Big Data Analytics Unit (BDAU) Secure Data Environment (SDE) at ICL there will be no transfer of data to any other location, with the exception of data that is aggregated with small numbers suppressed that may need to be extracted for inclusion in reports and outputs.

Data will be stored on servers at the ICL Data Centre (located in buildings owned and managed by ICL). The data held on the BDAU SDE can be accessed remotely (via a screen view) over a Virtual Private Network (VPN) that uses Multi-Factor Authentication (MFA). Personal data, as defined by the GDPR, will always remain on the servers at ICL. Personnel are prohibited from downloading or copying personal data to local devices.

The data will not leave England at any time.

Access is restricted to employees or agents of ICL who have authorisation from the Chief Investigator. All such individuals are substantive employees of ICL.

All personnel accessing the data have received appropriate training in data protection and confidentiality, this is reviewed once a year.

The data will not be linked with any other data.

There will be no requirement and no attempt to reidentify individuals when using the data. Given the rarity of Genital HSIL and/or SCC and Anal HSIL and/or SCC, ICL has requested the data items at the least granularity possible to limit any possibility of identification (i.e requesting a five-year age band instead of age).

Researchers from ICL will process the data for the purposes described above.

The expected outputs of the processing will be:

• Submission to peer-reviewed journals. The study team are aiming for publication in 2023 and plans to submit to Cancers, an MDPI open-access journal.

• Presentations at the following conferences: the Association of Coloproctology of Great Britain and Ireland (ACPCBI) 2023 Annual Meeting, the European Society of Coloproctology (ESCP) 2023 Conference and the International Anal Neoplasia Society (IANS) Scientific Meeting 2023.

The outputs will not contain raw NHS England NDRS data, and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social Media

• Public Reports

Target dates for the production of outputs are scheduled for 6-12 months after receipt of the data.

The findings of this research study are hoped to contribute to evidence-based decision-making for policymakers, local decision-makers (i.e., doctors) and patients to inform best practices and improve patient care.

In England, it has not yet been established how many women with anal precancer/cancer have also been affected by genital precancer/cancer and this project aims to finally answer this question. This study aims to establish the size of this high-risk population in England. Doing so is important when considering the implementation of early cancer detection and prevention services on a national level. This has the potential to influence genital cancer guidelines to include anal cancer awareness as part of the overall patient management pathway.

Once established, the incidence of anal cancer in this patient population in England can be included as additional evidence demonstrating the relationship between anogenital pathologies; most systematic reviews are currently lacking data from England. This will in turn be helpful to better understand the proportion of women with anal cancer in this high-risk category and indirectly highlight the remaining proportion of high-risk women on which risk factors are still uncertain and research needs to focus on. Individuals who fall within high-risk groups can then be targeted for closer anogenital surveillance, potentially resulting in earlier diagnosis and more favourable outcomes.

This data request is hoped will also allow the study team to establish the average time gaps between the development of a genital and anal lesion, this will be important when devising screening programs and establishing the ideal time point for initiating screening for these high-risk women.

Investigation into the role of personal and sociodemographic risk factors on the stage at diagnosis and eventual patient outcomes has the potential to identify specific groups that receive a later diagnosis and/or worse outcomes. This could allow for strategies to educate these specific populations to seek medical attention when required and attend a screening for anogenital cancers, potentially leading to earlier diagnosis and improved outcomes for these specific groups.

Overall, it is hoped that through the publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

There is no yielded benefits as data has not yet been released in support of this study.