HPV DNA Detection and Genotyping in Basal-Like Breast Carcinoma: Insights into a Possible Viral Association

Objectives: High-risk human papillomavirus (HPV) has been implicated in breast carcinogenesis, but its role remains controversial. Basal-like breast carcinomas (BLCs) share morphological and immunophenotypic features with HPV-related squamous cell cancers. This study aimed to detect HPV DNA in BLCs, perform genotyping, and evaluate p16 expression as a surrogate marker of HPV infection. Methods: A total of 36 formalin-fixed, paraffin-embedded basal-like breast carcinomas were studied. Additionally, 10 patients with high-grade (G3) invasive ductal carcinoma of no special type (NOS), of a different molecular subtype, were included as a control group. Immunohistochemistry for p16 was performed, followed by DNA PCR using L1-type specific primers for HPV genotyping in all cases, irrespective of p16 status. Ten high-grade invasive ductal carcinomas served as controls. Results: p16 overexpression was observed in 28/36 BLCs (77.8%). Overall, HPV DNA was detected in 11/36 BLCs (30.6%). Among p16-positive BLCs, HPV DNA was detected in 10 cases (35.7%): HPV45 in 4 cases, HPV16 in 4 cases, and HPV18 in 2 cases. One additional BLC that was p16-negative tested positive for HPV16. In the control group, HPV16 DNA was found in 4/5 p16-positive cases. No double infections were identified in the BLC cohort. Conclusions: High-risk HPV DNA (types 16, 18, and 45) is present in a substantial subset of p16-positive basal-like breast carcinomas, suggesting a possible pathogenetic role for the virus in these aggressive tumors, although causality remains to be established. However, p16 is not an absolute surrogate for HPV in breast tissue, and molecular confirmation is required. Further studies with E6/E7 mRNA assays are needed to confirm viral transcriptional activity.