Core Outcome Measures in Squamous Intra-epithelial Precursor Lesions of the Anus (COrSIcA): Disease Measurement

Anal cancer is a Human Papilloma Virus (HPV) related cancer with approximately 1500 new cases in the UK per year (2016-2018). Although considered an uncommon cancer, incidence rates have increased threefold in the last 30 years. Initial treatment is chemoradiotherapy, with surgical options reserved for early-stage disease, incomplete response to chemoradiotherapy or disease recurrence. Both treatment modalities are associated with substantial short and long-term side effects. It is estimated that over 90 percent of anal cancer cases in the UK are preventable thus avoiding the associated morbidity and mortality.

A number of sub-populations are at increased risk of developing anal cancer and therefore represent potential targets for cancer prevention and early detection strategies. In addition, a recognised precursor lesion, known as anal intra-epithelial neoplasia (AIN) presents further opportunity for early detection and prevention. AIN can be further stratified into benign low-grade (aLSIL) and potentially cancerous high-grade squamous intra-epithelial lesion (aHSIL). AIN has some similarities to the precursor lesion of cervical cancer, known as CIN. While the natural history of CIN is well-quantified, and there is an evidence-based management strategy of screening and treatment of CIN, with reduction in incidence of cervical cancer, this is so far not the case in AIN.

The recently published 'Treatment in Preventing Anal Cancer in Patients with HIV and Anal High-Grade Lesions' trial (ANCHOR), a large, multi-centre, phase III randomised-controlled trial (RCT) of anal HSIL (aHSIL) treatment versus active monitoring without treatment in people living with HIV (PLWH) showed significantly lower risk of squamous cell carcinoma of the anus (SCCA) with aHSIL treatment than with active monitoring. The magnitude of the benefit observed in the treatment arm led to early closure of the trial (on ethical grounds) and allowed treatment to be offered to those in the active monitoring arm. The likely consequence of such significant findings will be a shift towards screening and treatment of aHSIL and an era of AIN treatment trials to determine the optimal approach.

There are multiple treatments for aHSIL broadly categorised as medical (for example, topical imiquimod, 5-FU, and anti-viral agents such as cidofovir) and surgical (laser, infra-red coagulation, electrocautery, and local excision) therapies. Vaccination is a possible third management strategy. The evidence base underpinning such treatments is of poor quality and the optimal approach cannot be defined.

Assessment of changes in disease burden is an important feature in the clinical evaluation of a treatment. In the context of anal intra-epithelial lesions, clinical assessment involves digital anorectal examination combined with either direct ('naked eye') visual inspection of the anal canal and peri-anus (non HRA), and or visualisation under magnification using a technique known as high resolution anoscopy (HRA). A diagnosis of aHSIL is confirmed histologically following biopsy of suspicious lesions.