Awan Usman Ayub, Bashir Shaarif, Hassan Usman, Khan Sadiq Noor, Awan Faryal Mehwish, Jabbar Abdul, Khan Suliman, Guo Xingyi
Department of Medical Laboratory Technology, The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan.
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Infect Agent Cancer. 2025 Aug 13;20(1):55. doi: 10.1186/s13027-025-00668-w.
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.
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).
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%).
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.
乳腺癌是一项重大的全球健康挑战，其与人类乳头瘤病毒（HPV）的潜在联系值得研究。本研究调查了巴基斯坦乳腺癌患者中人类乳头瘤病毒（HPV）的患病率、基因型分布及其与临床病理的相关性。
这项单机构横断面研究纳入了2019年1月至2023年12月期间收集的501例女性患者的福尔马林固定石蜡包埋（FFPE）乳腺癌标本和110例良性对照。通过高灵敏度实时聚合酶链反应（PCR）检测高危（HR）HPV DNA，并使用INNO-LiPA基因分型Extra II检测法进行基因分型。分析临床病理数据，包括肿瘤分级、大小、淋巴结转移和受体状态，以确定其与HPV感染的相关性。统计分析采用Kruskal-Wallis检验分析连续变量，采用Fisher精确检验或卡方检验分析分类变量（p < 0.05）。
与其他状态相比，10.5%的乳腺癌病例（n = 53/501）检测到HPV DNA，其中HR基因型占主导（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毫米以及32.1%的N3期疾病，HR-HPV的患病率随着肿瘤分期增加且具有统计学意义（p < 0.05）。浸润性导管癌（34%）和浸润性小叶癌（28.3%）是最常见的组织学亚型。化生性癌的平均肿瘤大小最大（86.4±74.6毫米），HPV-16患病率最高（28.6%），且与HR-HPV感染有关。HPV发病高峰出现在51至60岁的患者中（37.7%）。在地理分布上，HPV-16在拉合尔（50%）和白沙瓦（60%）占主导。
本研究将HR-HPV与侵袭性乳腺癌联系起来，HPV-16和-18在城市地区占主导。此外，研究强调了靶向疫苗接种以及针对亚型特异性肿瘤发生机制研究的重要性。
