人乳头瘤病毒、烟草和口腔卫生不良可能协同作用，调节核因子 kappa B 信号通路的表达，从而促进巴基斯坦人群头颈部癌症的发生和发展。

Human papillomavirus, tobacco, and poor oral hygiene can act synergetically, modulate the expression of the nuclear factor kappa B signaling pathway for the development and progression of head and neck cancer in the Pakistani population.

机构信息

Department of Biochemistry, Qauid-i-Azam University, Islamabad 45320, Pakistan.

Department of Oral and Dental health, College of Applied Health Sciences in Arrass, Qassim University, Buraidah, Al Qasim 51921, Saudi Arabia.

出版信息

Chin Med J (Engl). 2022 Aug 5;135(15):1829-1836. doi: 10.1097/CM9.0000000000001970.

DOI:10.1097/CM9.0000000000001970

PMID:35838554

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9521783/

Abstract

BACKGROUND

Head and neck cancers (HNCs) are a heterogeneous group of tumors that progress owing to varied enviromental and genetic risk factors. Viral infections are threatening and adept at altering the expression of cellular transcription factors such as nuclear factor kappa B (NF-κB) and deregulation of other cellular proteins like NF kappa B inhibitor alpha (IκBα). The present study was conducted to detect high-risk genotypes of human papillomavirus (HPV) and protein expression of NF-κB signaling pathway in HNC patients with HPV infection.

METHODS

For HPV detection, genomic DNA from 152 HNC tumors was extracted formalin-fixed paraffin-embedded tissue DNA kit. For genotyping, polymerase chain reaction (PCR) using a general primer, HPV type-specific primers and agarose gel electrophoresis were performed. Immunohistochemistry (IHC) was also performed on 4-μm thick tissue sections using HPV E6 monoclonal antibody. Protein expression analysis of NF-κB signaling pathway including p50, p65, and IκBα was performed using IHC.

RESULTS

PCR analysis showed that 24.3% (37/152) of HNC cases were HPV positive. Among HPV positive, 86.5% (32/37) were tobacco users, while among HPV negative, 66.9% (77/115) were tobacco users. A significant association of HPV positivity and tobacco user was observed by univariate analysis [ P < 0.01; odds ratio (OR): 0.310, 95% confidence interval (CI): 0.110 to 0.870]. More HPV positive patients were with poor oral hygiene (78.3%) when compared with patients with good oral hygiene (21.6%) [ P < 0.03, OR: 2.440, 95% CI: 1.650 to 3.600]. The results of the logistic regression analysis showed that age, tobacco use and oral hygiene are significant predictors ( P < 0.02). PCR and IHC staining results confirmed that HPV16 was predominant among HNC cases (64.8%) when compared with HPV18 (35.2%). Expression of NF-κB proteins (p50, p65, and IκBα inhibitor) were also observed in HPV and non-HPV infected HNC tissues. IHC expression of p50, and p65 showed nuclear staining, while IκBα inhibitor showed cytoplasmic staining. Protein expression in HPV cases was higher as compared to HPV naive cases ( P < 0.05).

CONCLUSIONS

From the study, it can be established that the use of tobacco, oral hygiene, and HPV infection may be synergistically involved in modulating the expression of NF-κB signaling pathway for the development and progression of HNC in the Pakistani population.

摘要

背景

头颈部癌症（HNCs）是一组异质性肿瘤，由于不同的环境和遗传风险因素而进展。病毒感染具有威胁性，并且能够巧妙地改变核因子 kappa B（NF-κB）等细胞转录因子的表达，并使其他细胞蛋白如 NF kappa B 抑制剂 alpha（IκBα）失活。本研究旨在检测 HPV 感染的 HNC 患者中高危型 HPV 基因型和 NF-κB 信号通路的蛋白表达。

方法

从 152 例 HNC 肿瘤的福尔马林固定石蜡包埋组织中提取基因组 DNA。使用通用引物、HPV 型特异性引物和琼脂糖凝胶电泳进行聚合酶链反应（PCR）进行 HPV 检测。还使用 HPV E6 单克隆抗体对 4μm 厚的组织切片进行免疫组织化学（IHC）。使用 IHC 分析 NF-κB 信号通路的蛋白表达，包括 p50、p65 和 IκBα。

结果

PCR 分析显示，24.3%（37/152）的 HNC 病例 HPV 阳性。在 HPV 阳性病例中，86.5%（32/37）为吸烟者，而在 HPV 阴性病例中，66.9%（77/115）为吸烟者。单因素分析显示 HPV 阳性与吸烟者之间存在显著相关性[P < 0.01；优势比（OR）：0.310，95%置信区间（CI）：0.110 至 0.870]。与口腔卫生良好的患者（21.6%）相比，HPV 阳性患者的口腔卫生状况较差（78.3%）[P < 0.03，OR：2.440，95%CI：1.650 至 3.600]。逻辑回归分析的结果表明，年龄、吸烟和口腔卫生是显著的预测因素（P < 0.02）。PCR 和 IHC 染色结果证实 HPV16 在 HNC 病例中占主导地位（64.8%），而 HPV18 占 35.2%。在 HPV 和非 HPV 感染的 HNC 组织中也观察到 NF-κB 蛋白（p50、p65 和 IκBα 抑制剂）的表达。HPV 和非 HPV 感染的 HNC 组织中也观察到 NF-κB 蛋白（p50、p65 和 IκBα 抑制剂）的表达。HPV 病例中的 NF-κB 蛋白表达高于 HPV 阴性病例（P < 0.05）。