Present and Future Research on Anal Squamous Cell Carcinoma

SIMPLE SUMMARY: This is an exciting moment in clinical research in the squamous cell carcinoma of the anus (SCCA). Historical barriers regarding this disease are vanishing thanks to the creation of research networks in this rare pathology, gained knowledge in tumor biology and its environment in this human papillomavirus (HPV)-induced disease in more than 90% of patients, and the arrival of taxane-based chemotherapy regimens as well as immunotherapies and its novel combinations. This review sheds light on the present and the future of research on SCCA, new understanding of its rational for ongoing clinical trials, with special focus in locally advanced and metastatic diseases. ABSTRACT: Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination clinical trials with an anti-PD1/L1 are ongoing in localized and advanced stages, in association with radiotherapy, chemotherapy, tumor vaccines, anti-CTLA4, anti-EGFR, or antiangiogenic molecules. Moreover, a new biomarker with high sensitivity and specificity such as HPV circulating tumor DNA (HPV ctDNA) by liquid biopsy, is improving not only the prognostic measurement but also the treatment strategy guidance for this disease. Finally, better understanding of potential targets is reshaping the present and future clinical research in this unique, HPV genotype-16-related disease in the great majority of patients.