An overview of clinical trials in anal cancer 1999-2024

Anal cancer (AC) is an uncommon malignancy. Clinical trials are crucial for improving prevention and treatment, but conducting research is challenging in this condition. This paper provides an overview of registered clinical trials in the prevention and treatment of AC between 1999 and 2024. AC trials were identified from the two main global trial databases: the International Clinical Trials Registry Platform and clinicaltrials.gov . Trials were categorized based on context and disease extent: pre-AC (pre-cancerous states), early AC (localized, curable disease), and advanced AC (metastatic and/or incurable disease). There were 251 trials identified: 55 pre-AC, 100 early AC, and 96 advanced AC. Only 10% were phase III studies. The number of trials increased over the 25-year period, particularly advanced AC trials since 2015. Trials listed as active totaled 109, of which 54% were actively recruiting. Most trials were conducted in high-income countries and only 38 were multinational. Underrepresented groups were immunosuppressed patients. Only one-third of trials were industry-sponsored, lower than most other cancer types. Although there has been a steady increase in AC trials, many research questions remain. Disparities are clear, with few trials in low-income countries, where the burden of disease is likely to grow as a consequence of less access to human papillomavirus (HPV) vaccination, which is likely to prevent disease. Clinical trials in AC rely mainly on academic consortia. • AC is an uncommon form of HPV-related cancer, but the incidence is increasing. • The clinical trial landscape of AC is informative for future studies. • Future studies need to include low- and middle-income countries and disparities. • Most trials are academic, with less industry sponsorship than for other cancers.