Genetic variability of human papillomavirus type 66 L1 gene among women presenting for cervical cancer screening in Chile

• Published in: Medical microbiology and immunology 2019-12, Vol.208 (6), p.757-771
• Main Authors: Balanda, Monserrat, Fernández, Jorge, Vergara, Nicolás, Campano, Constanza, Arata, Loredana, Martín, Héctor San, Ramírez, Eugenio
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amino acids; Antigens, Viral - genetics; Biomedical and Life Sciences; Biomedicine; Cancer screening; Capsid Proteins - genetics; Cervical cancer; Cervix; Chile - epidemiology; Cross-protection; Early Detection of Cancer; Epidemiology; Epitopes; Epitopes, B-Lymphocyte - genetics; Female; Genetic variability; Genetic Variation; Genotype; Health risks; Homology; Human papillomavirus; Humans; Immunodominance; Immunology; L1 gene; L1 protein; Lesions; Lymphocytes B; Medical Microbiology; Medical screening; Middle Aged; Mutation; Oncogene Proteins, Viral - genetics; Original Investigation; Papillomaviridae; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Phylogeny; Prevalence; Risk groups; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - epidemiology; Uterine Cervical Neoplasms - virology; Vaccines; Variability; Virology; Young Adult
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-019-00621-w

The high-risk human papillomaviruses (HR-HPVs) are involved in the development of cervical cancer. Nevertheless, there are differences in the oncogenic potential among them. HPV-16 and HPV-18 are associated with approximately 70% of cancer worldwide, and both types are the most extensively studied HR-HPV. Great variations in the prevalence of HR-HPV have been described in different countries. The impact of these variations on the epidemiology of lesions and cervical cancer is currently unknown. A high prevalence of HPV-66 has been detected in Chile. Here, we have analyzed the genetic variability of the L1 gene from HPV-66-infected Chilean women. Higher order interactions between identified mutations were analyzed by co-variation and cluster analyses. Antigenic-index alterations following L1 mutations and B-cell epitopes were predicted by BcePred algorithm. HPV-66 L1 sequences clustered phylogenetically into two main clades. The genetic variability in the HPV-66 L1 gene involved thirty nucleotide changes. Four of these were for the first time identified in this study. Some of these variants are embedded in the B-cell epitope regions. Amino acid homology in the immunodominant epitopes of HPV-66 L1 protein (DE, FG and H1 loops) was 42.9–59.1% and 28.6–68.9% compared with HPV-16 and HPV-18, respectively. The results of this research suggest that the neutralizing epitopes of HPV-66 are antigenically different compared to HPV-16 and HPV-18. Our findings show the need to perform new structural and immunological studies on HPV-66 L1 protein to evaluate the cross-protection conferred by current HPV vaccines.