HLA-C -35kb Expression SNP Is Associated with Differential Control of β-HPV Infection in Squamous Cell Carcinoma Cases and Controls

Abstract

A single nucleotide polymorphism (SNP) 35 kb upstream of the HLA-C gene is associated with HLA-C expression, and the high expressing genotype (CC) has been associated with HIV-I control. HLA-C is unique among the classical MHC class I molecules for its role in the control of viral infections and recognition of abnormal or missing self. This immunosurveillance is central to the pathogenesis of non-melanoma skin cancer (NMSC), and of squamous cell carcinoma (SCC) in particular. While sun exposure is a major risk factor for these cancers, cutaneous infections with genus β-HPV have been implicated in the development of SCC. We hypothesized that the high expression HLA-C genotype is associated with β-HPV infections. Therefore, we investigated the association between β-HPV serology and the −35 kb SNP (rs9264942) in a population-based case-control study of 510 SCC cases and 608 controls. Among controls, the high expression −35 kb SNP genotype (CC) reduced the likelihood of positive serology for multiple (≥2) β-HPV infections (OR = 0.49, 95% CI: 0.25–0.97), and β-HPV species 2 infection (OR = 0.43, 95% CI: 0.23–0.79). However, no association with β-HPV status was observed among SCC cases. Our findings suggest that underlying immunogenotype plays an important role in differential control of β-HPV in SCC cases and controls.

A genome‐wide association study in Caucasian women suggests the involvement of HLA genes in the severity of facial solar lentigines

“…The set of SNPs in the 6p21 region in high LD with the allele HLA‐C*0701 allele ( r 2 = 0.95) has also been associated with decreased expression of the HLA‐C genes by several independent eQTL databases, although this must be interpreted with caution because of the high degree of genetic variability and LD across the HLA region (Cookson et al., ). On the contrary, high expression of HLA‐C has been associated with the control of β ‐HPV induced squamous cell carcinoma (Vineretsky et al., ). This observation could suggest a control mechanism in abnormal skin cells through HLA‐C recognition, with aberrant melanocytes not being eliminated by the surveying immune cells.…”

Immunogenetics and human papillomavirus (HPV) in male genital lichen sclerosus (MGLSc)

“…Also, HLA (especially HLA-C) may be a proxy for modulation of viral infections such as HPV. 10 Viral infections such as HPV have been certainly associated with penile SCC. This work was undertaken to explore further the roles and relationships of HLA and HPV in MGLSc.…”

Expression of classical HLA class I molecules: regulation and clinical impacts

“…In squamous cell carcinoma, −35 kb CC variant is associated with a differential control of the β‐HPV infection: less multiple infections by various β‐HPV and less infections by HPV type 2 .…”