HPV-driven breast carcinogenesis: associations with tumor severity, Ki67 expression and metastasis.

IF 2.8 2区医学 Q3 IMMUNOLOGY

Infectious Agents and Cancer Pub Date : 2025-08-13 DOI:10.1186/s13027-025-00668-w

Usman Ayub Awan, Shaarif Bashir, Usman Hassan, Sadiq Noor Khan, Faryal Mehwish Awan, Abdul Jabbar, Suliman Khan, Xingyi Guo

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引用次数: 0

Abstract

Objective: Breast cancer (BC) poses a significant global health challenge, and its potential link to HPV warrants investigation. This study investigates the prevalence, genotype distribution, and clinicopathological associations of human papillomavirus (HPV) in breast cancer patients from Pakistan.

Methods: This single-institutional cross-sectional study included 501 FFPE BC specimens from female patients and 110 benign controls, collected between January 2019 and December 2023. High-risk (HR) HPV DNA was detected via highly sensitive real-time PCR, with genotyping conducted using the INNO-LiPA Genotyping Extra II assay. Clinicopathological data, including tumor grade, size, lymph node metastasis, and receptor status, were analyzed for associations with HPV infection. Statistical analyses employed the Kruskal-Wallis test for continuous variables and Fisher's exact or chi-square tests for categorical variables, as appropriate (p < 0.05).

Results: HPV DNA was detected in 10.5% of BC cases (n = 53/501) compared to other statuses, with HR genotypes predominating (91%). HPV-16 (26%) and HPV-18 (15%) were the most frequent genotypes. HPV-positive cases exhibited aggressive tumor characteristics, including 58.5% grade III tumors, a mean tumor size of 65.6 ± 46.4 mm, and 32.1% N3 disease, with an increasing prevalence of HR-HPV associated with tumor stage and significance (p < 0.05). Invasive ductal carcinoma (34%) and invasive lobular carcinoma (28.3%) were the most common histological subtypes. Metaplastic carcinomas, with the largest mean tumor size (86.4 ± 74.6 mm), showed the highest HPV-16 prevalence (28.6%) and were linked to HR-HPV infection. Peak HPV incidence occurred in patients aged 51-60 years (37.7%). Geographically, HPV-16 predominated in Lahore (50%) and Peshawar (60%).

Conclusion: This study links HR-HPV to aggressive BC, with HPV-16 and -18 predominating in urban areas. Additionally, it highlights the importance of targeted vaccination and research into subtype-specific oncogenesis.

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hpv驱动的乳腺癌发生：与肿瘤严重程度、Ki67表达和转移的关系。

目的：乳腺癌（BC）构成了重大的全球健康挑战，其与HPV的潜在联系值得调查。本研究调查了巴基斯坦乳腺癌患者中人乳头瘤病毒（HPV）的患病率、基因型分布和临床病理相关性。方法：这项单机构横断面研究包括2019年1月至2023年12月期间收集的女性患者的501例FFPE BC标本和110例良性对照。高风险（HR） HPV DNA通过高灵敏度实时PCR检测，并使用INNO-LiPA基因分型Extra II试验进行基因分型。临床病理数据，包括肿瘤分级、大小、淋巴结转移和受体状态，分析与HPV感染的关系。统计分析对连续变量采用Kruskal-Wallis检验，对分类变量采用Fisher精确检验或卡方检验(p)。结果：与其他状态相比，10.5%的BC病例（n = 53/501）检测到HPV DNA， HR基因型占主导地位（91%）。HPV-16（26%）和HPV-18（15%）是最常见的基因型。hpv阳性病例表现出侵袭性肿瘤特征，包括58.5%的III级肿瘤，平均肿瘤大小为65.6±46.4 mm， 32.1%的N3疾病，并且随着肿瘤分期和意义的增加，HR-HPV患病率增加(p结论：本研究将HR-HPV与侵袭性BC联系起来，HPV-16和-18在城市地区占主导地位。此外，它强调了靶向疫苗接种和研究亚型特异性肿瘤发生的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY

CiteScore

5.80

自引率

2.70%

发文量

期刊介绍： Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.