Non-melanoma skin cancer in HIV infection: the role of human papillomavirus (HPV), individual immunogenotype (HLA ‘tissue type’) and Merkel cell polyomavirus (MCV)

Abstract

Non-melanoma skin cancer (NMSC) in HIV presents increasing problems e.g. incidence and morbidity. Ultraviolet light and human papillomavirus (HPV) are implicated in NMSC pathogenesis. In HIV, HPV is unequivocally involved in oral, anogenital and cervical squamous cell cancer (SCC) but its role in cutaneous SCC is unclear. Merkel cell polyomavirus (MCV), the cause of Merkel cell carcinoma, has not been investigated in NMSC in HIV. HLA immunogenotype characterises some dermatoses in HIV and associations with NMSC have been reported in organ transplant recipients, but its role in HIV NMSC is unknown.

HIV+ve cases and HIV–ve controls (each n=58) with NMSC and NM pre-cancer were identified. DNA was extracted from tissue (n=113, n=123 samples respectively) for broad-spectrum HPV/MCV typing and blood (n=107) for HLA typing by specific and sensitive PCR-based methodologies.

HIV samples showed higher overall HPV prevalence (51%/41% HIV-ve). Genital types were more prevalent (47%/44%) than beta (36%/36%) or wart types (17%/20%). High risk (HR) types (69%/60%; 74%/77% from non-genital skin) and multiple types were more prevalent (19%/14%), but only the differences between genital and wart types were statistically significant (Yates: p<0.05). Of all NMSC/pre-cancer samples, 23% were MCV+ve; 39% HIV+ve; 36% MCV+ve were HPV co-infected (no difference between groups). Several HLA associations were found; one, HLA-DQA1*01 (controls) was significant (Bonferroni: p<0.05). HPV is prevalent in HIV+ve/HIV-ve NMSC/pre-cancer supporting a carcinogenic role. Although isolated mainly from extragenital skin, genital types were the most common in both groups; beta types previously reported as commonest in NMSC. HR types seemed more prevalent in HIV. Overall HPV prevalence and HR and multiple types seem more prevalent in HIV NMSC/precancer (although not statistically significant), possibly reflecting immune status differences. MCV, is prevalent in NMSC/pre-cancer, regardless of HIV or HPV; its part in carcinogenesis remains unclear. HLA immunogenotype may play a role in NMSC pathogenesis.