Purpose <p>Breast cancer (BC) persists as a substantial public health concern, with viral infections such as <i>Human Papillomavirus</i> (HPV) increasingly identified as a contributing factor in its development and progression. This study aimed to examine the prevalence and genotypic distribution of HPV in breast cancer cases among Moroccan women and to explore its potential association with clinicopathological factors.</p> Methods <p>HPV DNA was analyzed in invasive breast cancer biopsies and control samples using nested polymerase chain reaction (PCR) and Sanger sequencing. Clinicopathological data, including histoprognostic grade, tumor stage, and hormone receptor status, were evaluated to identify potential correlations with HPV infection.</p> Results <p>The analysis revealed that HPV DNA was detected in 52% of breast cancer cases<b>,</b> indicating a significant association with breast cancer development. The most prevalent high-risk genotypes were HPV 16 (65.4%) and HPV 45 (23.1%). Significant correlations were observed between HPV infection and several parameters, including histoprognostic grade (<i>p</i> &lt; 0.001), tumor stage (<i>p</i> = 0.045), progesterone receptor (<i>p</i> &lt; 0.001), and estrogen receptor (<i>p</i> = 0.039). Sequence analysis revealed a high degree of genetic similarity with HPV strains from Iran and France.</p> Conclusion <p>These findings suggest a significant link between HPV infection and breast cancer, with HPV 16 as the dominant genotype. These findings suggest that HPV-DNA could be a valuable biomarker for assessing breast cancer risk, supporting the need for enhanced screening and vaccine development. Further research in diverse populations is essential to confirm these results.</p>