Abstract 4898: The contribution of human papilloma virus infection to cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia
Authors: Bhavsar Preeya , Hamza Mugahed , Mehravaran Sepideh , He Qin , Tyring Steven , Rady Peter , Krishnan Bhuvaneswari , Rivero Gustavo , Cohen Daniel N. , Sosa Iberia Romina 
Published: September 2020

Abstract
Background:
Human papilloma virus (HPV) is the most common sexually transmitted disease worldwide. α-genus HPV have oncogenic potential in anogenital skin and mucosa. Transplant patients have an increased incidence of β-genus HPV-associated cutaneous squamous cell carcinoma (cSCC). The host immune system is particularly important in the pathogenicity of HPV infection. The antibody-mediated, humoral immune response clears virus particles from body fluids and prevents re-infection. Cell-mediated immunity clears the virus from infected cells, generating immune memory. Impaired cell-mediated immunity is considered a primary risk factor in HPV-induced cSCC in the immunosuppressed population.
Patients with chronic lymphocytic leukemia (CLL), a B-cell malignancy characterized by impaired humoral immunity, are at increased risk of developing cSCC. The purpose of this study is to explore the potential role of HPV in malignancies with impaired humoral response.
Methods
Primary cSCC tissue DNA was isolated from patients diagnosed with CLL. The tissue was analyzed for the presence of HPV. Diagnostic specimens underwent consensus dermatopathology review. Peripheral blood analytes and clinical parameters for disease course were statistically analyzed in conjunction with histopathology.
Results
Eleven patients with CLL contributed 37 cSCCs. In 49% of the lesions, HPV was detected. Among the cSCC lesions, 27% of the lesions contained β-genus HPV and 30% contained α-genus HPV. The most frequently reported virus was HPV-27 (α-genus), with 16% of lesions containing this variant which is frequently associated with cutaneous warts rather than cSCC. A majority of the HPV-containing lesions displayed moderate dermal lymphocytic inflammation. The lesions were often documented in sun exposed areas such as the scalp and face. Interestingly, HPV-16 and HPV-18, often found in anogenital epithelia, were detected in sun exposed skin in 14% of the lesions examined. In those patients who had documented immunoglobulins, all had hypogammaglobulinemia.
Conclusions
We examined clinical, histopathologic, and viral genotypes of the cSCCs in patients with CLL. It is widely accepted that CLL patients have a higher incidence and recurrence of cSCC; however, the characteristics of the lesions and the potential association to HPV has not been reported. In our cohort, the lesions were as likely to contain HPV from the α- or β- genus. HPV-27, normally associated with warts, displayed an atypical pathology. The presence of HPV-16 and -18 in sun exposed areas, suggests a novel pathology in compromised humoral immunity. Although our analysis derived some interesting associations, the role for HPV in cSCC in patients with impaired humoral immunity requires further characterization. This is particularly important as we explore the role of vaccinations in reducing HPV-associated malignancies.
Citation Format: Preeya Bhavsar, Mugahed Hamza, Sepideh Mehravaran, Qin He, Steven Tyring, Peter Rady, Bhuvaneswari Krishnan, Gustavo Rivero, Daniel N. Cohen, Iberia Romina Sosa. The contribution of human papilloma virus infection to cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4898.