S1980 Resolution of High-Grade Anal Squamous Intraepithelial Lesion With Antibiotics Proposes a New Role for Syphilitic Infection in Potentiation of HPV-Associated ASCC

Abstract

Introduction: Human Papilloma Virus (HPV) is the primary risk factor for the development of Anal Intraepithelial Neoplasia (AIN) and is a leading risk factor for anogenital squamous cell carcinoma (ASCC). Despite common shared risk factors for both HPV and syphilis, co-infection is not well documented, and the role of syphilitic infection in HPV-associated AIN and ASCC potentiation is not defined. Case Description/Methods: A 72-year-old male presented with complaints of mild rectal pain and intermittent rectal bleeding. A flexible sigmoidoscopy was performed, and an anal mass was detected and biopsied. Pathology findings included evidence of a high grade squamous intraepithelial lesion (HGSIL, AIN II/II/AIS) with viral cytopathic effect, consistent with HPV infection. Much of the biopsied lesion demonstrated acanthotic squamous mucosa with intraepithelial neutrophils and abundant submucosal plasma cells, suggesting possible syphilitic involvement. Subsequent immunohistochemical staining for P16 as a surrogate marker for HPV was positive, as was an immunohistochemical stain for spirochetes, supportive of co-infection with Treponema pallidum, the causative agent in syphilis. The patient was referred to an infectious disease specialist and his syphilis was treated with penicillin. Upon follow up with gastroenterology, remarkable near-complete resolution of the suspected HPV actuated dysplastic lesion was observed. Discussion: Resolution of the lesion by antibiotic treatment for syphilitic infection suggested that co-infection by Treponema pallidum may potentiate HPV-associated squamous cell carcinoma based on histological findings. Findings from this case, as well as a review of bacterial involvement and potentiation in various cancers, are reviewed here. Such findings offer new insight regarding the role of STD-associated bacteria and HPV co-infection in the establishment of AIN and may additionally propose new treatment modalities for ASCC.Figure 1.: Co-infection by HPV and syphilis in high grade squamous anal intraepithelial lesion. A. P16 staining demonstrates HPV positivity. B. Hematoxylin and eosin staining of tissue fragment that demonstrated positivity for P16 confirms HPV infection. C. Spirochete stain confirms the presence of Treponema pallidum and syphilitic infection with HPV.