Clarifying the demographics and risk factors of patients with anal intraepithelial neoplasia and anal squamous cell carcinoma

Abstract

Anal Squamous Cell Carcinoma (ASCC) is an uncommon Human Papillomavirus (HPV) related malignancy that has been rapidly increasing in incidence. Its known risk factors include HIV, immunosuppression and previous HPV-related malignancies. ASCC has a precursor; Anal Intraepithelial Neoplasia (AIN), and although there are comprehensive guidelines on the management of ASCC, the evidence for the screening for and treatment of AIN as well as the prevention of ASCC is very poor. There is also little understanding into the genetic natural history of ASCC and the reasons why some patients with AIN progress to ASCC and whereas others regress spontaneously. It has been suggested that the increasing risk of ASCC is related to people living with HIV (PLWH) living longer on advanced antiretrovirals; however, most patients with ASCC are women diagnosed later in life who are not known to have HIV. It is therefore likely that there are hidden risk factors contributing to the rise in incidence. By exploring the demographics of patients with ASCC in England as well as examining the differences in presentation patterns in patients with ASCC in a high HIV prevalence cohort it is hoped that the risk profiles of the patients with increasing incidence can be clarified. A pilot study was also completed investigating whether the genetic predeterminants that drive the progression of AIN to ASCC can be identified. This thesis demonstrates that although a PLWH subgroup with increasing incidence has been identified, their outcomes are excellent when compared to the “lost tribe” of women who are being diagnosed with late-stage and metastatic disease at an alarming incidence in England. It is possible that this subgroup are women, who have been successfully treated for cervical dysplasia, but then have persisting HPV infections that progress to ASCC later in life. Further study into improving this subgroup’s outcomes is urgently required.