HLA-DP is the cervical cancer susceptibility loci among women infected by high-risk human papillomavirus: potential implication for triage of human papillomavirus-positive women

Abstract

Given that only a small proportion of women infected by high-risk human papillomavirus (hrHPV) develop cervical cancer, it's important to identify biomarkers for distinguishing women with hrHPV positivity who might develop cervical cancer from the transient infections. In this study, we hypothesized that human leukocyte antigens (HLA) susceptibility alleles might contribute to cervical cancer risk among females infected by hrHPV, and interact with hrHPV types. A case-control study with 593 cervical cancer cases and 407 controls (all hrHPV positive) was conducted to evaluate the effect of eight HLA-related single-nucleotide polymorphisms (SNPs) and their interactions with hrHPV types on the risk of cervical cancer. Three HLA-DP SNPs (rs4282438, rs3117027, and rs3077) were found to be significantly associated with risk of cervical cancer (rs4282438: odds ratio (OR) = 0.72, 95 % confidence interval (CI) = 0.56-0.93; rs3117027: OR = 1.41, 95 % CI = 1.10-1.83; and rs3077: OR = 1.37, 95 % CI = 1.04-1.80) among women infected with hrHPV. An additive interaction between HPV16 and rs4282438 for cervical cancer risk was also found (P for interaction = 0.002). Compared with subjects carrying variant genotypes (GG/TG) and non-HPV16 infections, those carrying wild-type genotype (TT) of rs4282438 and HPV16 positive had a 5.22-fold increased risk of cervical cancer (95 % CI = 3.39-8.04). Our study supported that certain HLA-DP alleles in concert with HPV16 could have a predisposition for cervical cancer development, which may be translated for triage of hrHPV-positive women.

Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

“…For those participants with normal cytology, a colposcopy was not routinely used unless they were HPV16 or 18-DNA positive. High-risk HPV prevalence was 97.7% (593/607) in cervical cancer patients and 8.0% (407/5066) in cancer-free individuals [25]. In the current study, all HPV16/18positive controls accepted colposcopy and showed negative results.…”

The precision prevention and therapy of HPV‐related cervical cancer: new concepts and clinical implications

“…Interestingly, only a few months later, another study conducted with Norwegian patients also report similar susceptible loci DQA1 and DQB1 in the MHC region, with partial but not complete overlap . From then on, many more variants of MHC genes were discovered and confirmed to be correlated with cervical cancer in various populations . Wu et al.…”

“…Jia et al. . found three HLA‐DP SNPs (rs4282438, rs3117027, and rs3077) to be significantly associated with the risk of cervical cancer.…”

“…Wu et al [37].confirmed that the HLA-II DQB1*0602 allele was significantly increased in HPV16-infected patients with cervical cancer. Jia et al [36]. found three HLA-DP SNPs (rs4282438, rs3117027, and rs3077) to be significantly associated with the risk of cervical cancer.…”

Association of human leukocyte antigens‐DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population

“…The HLA-DP genetic variants have been recognized to correlate with occult hepatitis B infection (Mardian et al, 2017), and it has been shown that HLA-DQ polymorphisms as protective factors are connected to HBV-related hepatocellular carcinoma (Gao et al, 2016). Additionally, HLA-DP and HLA-DQ variants are involved in the progression of other diseases, such as graft-versus-host disease and cervical cancer (Jia et al, 2016;Morishima et al, 2018). HLA genes encode molecules that are central to the host immune response, and variation in these genes likely predicts the outcome of infectious diseases (Crux & Elahi, 2017).…”