An entropy-based framework for genomic variability analysis: A South American case study of human papillomavirus

The genetic diversity of Human Papillomavirus (HPV) poses challenges for molecular detection and genotyping, particularly in regions with distinctive circulating variants such as South America. This study aimed to quantitatively characterize HPV genomic variability using Shannon entropy (H) and to establish a reproducible framework for systematic variability assessment. Positional entropy was calculated across complete and partial HPV genomic sequences and aggregated by gene to compare intra- and intergenotypic conservation patterns using publicly available South American sequences. Intragenotypic analyses showed that most genomic positions were highly conserved (H ≈ 0), consistent with functional constraints. In contrast, intergenotypic comparisons revealed a dual pattern of variability: early genes E5, E6, and E7 displayed higher divergence, whereas capsid genes L1 and L2 were comparatively conserved. These patterns align with known functional and evolutionary constraints across HPV genes. Rather than proposing diagnostic implementations, these results provide a quantitative basis for the preliminary prioritization of conserved and variable genomic regions. Entropy profiling provides a quantitative framework for characterizing genomic variability and may support the identification of conserved and variable regions for future investigation and genomic surveillance efforts, although experimental validation is required to determine diagnostic performance. Overall, this work presents a reproducible and data-driven approach for assessing HPV genomic variability and contributes to the understanding of regional viral diversity in South America.