Dataset Information

Analysis of human leukocyte antigen associations in human papillomavirus-positive and -negative head and neck cancer: Comparison with cervical cancer.

ABSTRACT:

Background

Although the majority of human papillomavirus (HPV) infections are cleared by the immune system, a small percentage of them progress to develop HPV-driven cancers. Cervical cancer studies highlight that HPV persistence and cancer risk are associated with genetic factors, especially at the human leukocyte antigen (HLA) genes. This study was conducted to investigate such associations in head and neck cancer (HNC).

Methods

In all, 192 patients with HNC and 384 controls were genotyped with the Infinium Global Screening Array (Illumina, Inc). HLA variants were imputed with SNP2HLA, and an association analysis was performed by logistic regression.

Results

HPV-positive HNCs were significantly associated with single-nucleotide polymorphisms (SNPs) at DRB1_32660090 (P = 1.728 × 10^-6 ) and DRB1_32660116 (P = 1.728 × 10^-6 ) and with the amino acid variant DRB1_11_32660115 (P = 1.728 × 10^-6 ). None of these associations were observed in the HPV-negative cohort, and this suggested their specificity to convey risk for HPV-associated HNCs. In general, associations observed for HPV-negative HNC were relatively weak, and variants in the HLA-DPA1 region were the strongest among them (P = 4.531 × 10^-4 ). Several lead signals reported by previous HNC genome-wide association studies, including SNPs rs3135001 (P = .012), rs1049055 (P = .012), and rs34518860 (P = .029) and allele HLA-DQB1*06 (P = .009), were replicated in the current study. However, these associations were limited to the HPV-positive HNC group. Several cervical cancer-associated HLA variants, including SNPs rs9272143 (P = .002) and rs9271858 (P = .002) and alleles HLA-B-1501 (P = .009) and HLA-B-15 (P = .015), were also exclusively associated with HPV-positive HNC.

Conclusions

HPV-positive HNC risk is associated with distinct HLA variants, and some of them are shared by both cervical cancer and HPV-positive HNC. Human papillomavirus (HPV)-positive head and neck cancer (HNC) risk is associated with distinct human leukocyte antigen variants, and some of them are shared by both cervical cancer and HPV-positive HNC.

Lay summary

Cervical cancer studies highlight that human papillomavirus (HPV)-driven cancer risk is linked with human leukocyte antigen (HLA) polymorphism. Hence, the current study was designed to investigate the HLA associations in HPV-positive and HPV-negative head and neck cancer (HNC) and compare these associations with cervical cancer. Several lead signals reported by previous HNC and cervical genome-wide association studies were replicated in the current study. However, these associations were limited to the HPV-positive HNC group, and this suggests that HPV-positive HNC risk is associated with distinct HLA variants, and some of them are shared by both cervical cancer and HPV-positive HNC.

SUBMITTER: Ekanayake Weeramange C

PROVIDER: S-EPMC9306518 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Importance:Prospective studies are needed to examine the temporal relationship between oral human papillomavirus (HPV) detection and risk of head and neck squamous cell carcinoma (HNSCC). Moreover, the oral cavity contains a wide spectrum of ?-, ?-, and ?-HPV types, but their association with risk of HNSCC is unknown. Objective:To prospectively examine associations between ?-, ?-, and ?-HPV detection in the oral cavity and incident HNSCC. Design:A nested case-control study was carried out among 96?650 participants, cancer free at baseline, with available mouthwash samples in 2 prospective cohort studies: (1) the American Cancer Society Cancer Prevention Study II Nutrition Cohort and (2) the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident cases of HNSCC (n?=?132) were identified during an average 3.9 years of follow-up in both cohorts. Three controls per case (n?=?396) were selected through incidence density sampling and matched on age, sex, race/ethnicity, and time since mouthwash collection. Methods:Through a next-generation sequencing assay, DNA from ?-, ?-, and ?-HPV types were detected. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs, adjusting for smoking history, alcohol consumption, and detection of HPV-16 for ?- and ?-HPVs. Main Outcomes and Measures:Incident HNSCC, which includes cancers of the oropharynx, oral cavity, and larynx. Results:A total of 132 participants developed HNSCC during the follow-up period (103 men and 29 women; average age at baseline, 66.5 years). Oral HPV-16 detection was associated with incident HNSCC (OR, 7.1; 95% CI, 2.2-22.6), with positive association for oropharyngeal SCC (OR, 22.4; 95% CI, 1.8-276.7), but not for oral cavity (OR, 4.5; 95% CI, 0.6-34.7) or laryngeal SCCs (OR, 0.11; 95% CI, 0.01-834.80). Detection of ?1-HPV-5 and ?2-HPV-38 types, as well as ?-11 and ?-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P?<?.01 for all comparisons). Detection of ?1-HPV-5 type was associated with oropharyngeal (OR, 7.42; 95% CI, 0.98-56.82; P?=?.054), oral cavity (OR, 5.34; 95% CI, 1.51-18.80; P?=?.01), and laryngeal SCCs (OR, 2.71; 95% CI, 1.00-7.43; P?=?.05), whereas ?11- and ?12-HPV species were associated with both oral cavity (OR, 7.47; 95% CI, 1.21-46.17; P?=?.03; and OR, 6.71; 95% CI, 1.47-30.75; P?=?.01, respectively) and laryngeal SCCs (OR, 7.49; 95% CI, 1.10-51.04; P?=?.04 and OR, 5.31; 95% CI, 1.13-24.95; P?=?.03, respectively). Conclusions and Relevance:This study demonstrates that HPV-16 detection precedes the incidence of oropharyngeal SCC. Associations of other HPVs, including ?11- and ?12-HPV species and ?1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.