Pilot study of Anal Neoplasia Treatment in people with HIV Evaluation and monitoring (short title: PANTHER)

Anal high grade squamous intraepithelial lesions (HSIL) are caused by high-risk human papillomavirus (HRHPV) and may develop into anal cancer. Anal cancer is rare in the general community, however people who live with HIV (PLHIV) are at higher risk. Anal HSIL is detected by high resolution anoscopy (HRA). Electrocautery, also known as thermal cautery, refers to a process in which a current is passed through a metal tip/electrode. The heated tip is then applied to the anal HSIL to ablate the tissue and has the advantage of not impacting surrounding normal tissues. During electrocautery, the current only flows through the tip, which burns the tissue by direct transfer of heat. With adequate anaesthesia, the discomfort caused by the treatment will be minimised. The electrocautery procedure takes around 10-20 minutes to perform. Electrocautery is commonly used in treating skin, eye conditions and other minor surgery. It is currently used in other countries to treat anal HSIL. Until 2023, there was a lack of evidence that treating anal HSIL reduces the risk of anal cancer and most anal HSIL in Australia is closely monitored and not treated. In this study, study participants will receive up to five electrocautery treatments during a six-month treatment period. There will be one follow-up visit with HRA and biopsy twelve months after the last treatment visit/the last clearance. Electrocautery treatment will be conducted by sexual health physicians and colorectal surgeons who are trained High Resolution Anoscopists at St Vincent's Hospital Sydney. Up to five electrocautery treatments will be conducted. There will be a gap of four to six weeks between treatments. Treatment assessments and electrocautery treatments will be repeated four to six weekly until HSILs have completely cleared at two consecutive assessment visits or participants have received a maximum of five treatments but HSILs have not completely cleared or have not cleared at all. For example, if a participant has received electrocautery treatment at the Baseline visit (first treatment visit) and their HSILs have completed cleared in two consecutive assessment visits (4–6 weeks apart), they will not require to receive any more treatment. Their next visit will be the follow-up visit. If their HSILs have partially cleared or not cleared at all after five treatments, they will not receive any more treatments and their next visit will be the follow-up visit. Adherence to the intervention and post-treatment care is important to the safety and comfort of the participants, and the outcome of the intervention. Study clinicians will ensure participants understand the research nature of the study, the risks and potential benefits, the implications of their participation, and the importance of adhering to the intervention during the informed consent process. Participants will be provided with written and verbal information of how to prepare for the electrocautery treatment and the after care to reduce discomfort or the likelihood of adverse events. Discomfort during treatment will be minimised by numbing agents in the form of cream and injections and study clinicians will ensure the participants have adequate pain cover. Participants will be completing a symptom diary after each treatment and their symptoms/adverse events will be closely monitored and addressed by their study clinicians to help adherence. The study research assistant at St Vincent’s Hospital will follow-up with participants if they miss any scheduled appointments and refer them to the study clinicians if participants have any concern of returning to the clinic for subsequent visits. However, study clinicians will make it very clear to the participants that they can withdraw at any time during the study if they changed their mind or if their situation changed and they no longer wanted to receive the study treatment or attend any study visits. They will be assured that withdrawal from participation will not affect their ongoing care at the clinic.