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

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.