Investigation of Human papillomavirus Type 16’s genetic polymorphism, pathogenicity, and persistent infection capacity

Limited research has explored the relationships among genetic polymorphisms, viral load, adaptability, persistence, and pathogenicity of human papillomavirus (HPV) type 16. Understanding these associations is essential for clarifying HPV16 pathogenic mechanisms and improving prevention, screening, and control strategies. Methods: Female subjects attending three hospitals in Baghdad, Iraq—Al-Alawiyah Hospital, Al-Habibyah Hospital, and Baghdad Teaching Hospital—were enrolled. Exfoliated cervical cell samples were collected. HPV genotyping and viral load quantification were performed using real-time fluorescence polymerase chain reaction (PCR), and the E6 and E7 oncogenes were sequenced using Sanger sequencing. Analyses focused on temporal trends in HPV16 detection, distribution of HPV16 lineages and sublineages (A–D), and E6/E7 sequence variants. Associations between viral lineage, viral load, pathogenicity, and persistence were also evaluated. Results: Of 3,453 samples analyzed, HPV infection was detected in 974 individuals. HPV16 was identified in 162 HPV-positive cases, yielding an overall prevalence of 6.16%. Significant differences in HPV16 detection rates were observed between 2022 and 2025. The HPV16 lineage A prototype, with E6 and E7 sequences identical to the reference genome, was the most prevalent lineage. This dominant lineage was associated with an increased risk of persistent infection and cervical disease, including cervical intraepithelial neoplasia and cervical cancer. Viral load differed significantly between disease and lesion-free groups, as well as between persistent infection and viral clearance groups. No significant association was observed between viral load and E6/E7 mutations (E6 L83V or E7 N29S). Conclusions: The HPV16 lineage A prototype plays a key role in viral pathogenicity and persistence. Viral load correlates positively with disease severity and persistence, suggesting its potential utility as a clinical biomarker. Further studies are needed to clarify additional molecular mechanisms underlying HPV16 evolution and adaptation.