Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective

Area of Science:

• Virology
• Oncology
• Genetics

Background:

• Human papillomavirus type 16 (HPV-16) is a major cause of invasive cervical cancer worldwide.
• Intratype variation within HPV-16 can influence viral oncogenesis and vaccine efficacy.
• Previous studies have identified several HPV-16 lineages, but comprehensive global characterization is ongoing.

Purpose of the Study:

• To investigate the global distribution and genetic diversity of HPV-16 variants in invasive cervical cancer tumors.
• To identify novel HPV-16 variants and characterize their genetic alterations.
• To explore the phylogenetic relationships of HPV-16 variants across different geographic regions.

Main Methods:

• Analysis of HPV-16 DNA from 408 cervical tumor samples collected internationally.
• Utilized E6 and L1 PCR-based hybridization systems to identify HPV-16 variant lineages.
• Sequencing of E6, L1 (MY09/11 region), and long control region for novel variants.

Main Results:

• Identified 32 (7.8%) novel HPV-16 variants with unique hybridization patterns or nucleotide changes.
• Phylogenetic analysis revealed distinct geographic clustering: European (E) variants in Europe/North America, African (Af1, Af2) in Africa, Asian (As) in Southeast Asia, and Asian American (AA) in the Americas/Spain.
• Observed 11 novel combined E6-L1 hybridization patterns in 21 samples, with no evidence of significant genomic recombination between major HPV-16 lineages.

Conclusions:

• This study provides an extensive description of global HPV-16 intratype variation.
• The identified HPV-16 variants offer a basis for understanding functional differences and their impact on biological activities.
• Characterization of HPV-16 variants is important for refining cervical neoplasia risk assessment and guiding HPV-16 vaccine development strategies.