Description
ObjectivesCervical squamous cell carcinoma, which is predominantly caused by high-risk human papillomaviruses (hrHPV), is the fourth most prevalent cancer among women. This study aimed to investigate the genomic variability of HPV16 (the most oncogenic hrHPV type) isolates from Latvia and compare their genetic makeup with isolates originating elsewhere.
Materials and Methods
Local women (n=84), aged 42.2±10.1 years, participated in a prospective study (Ethical approval: RSU N2-PĒK-4/415/2022) and regularly visited a gynecologist. Cervical biopsies were collected, formalin-fixed, and paraffin-embedded in case of the observed pathologies. DNA was extracted and analyzed for 14 hrHPV genotype presence using PCR (AllplexHPV14, Seegene). Samples with high HPV16 load (n=24) underwent whole genome sequencing using the Illumina platform. Demultiplexed reads were mapped onto the human genome reference extended by an HPV16 reference genome. Variant analysis and isolate consensus sequence generation were done using iVar. Evolutionary analyses within a global context were performed using the custom-tuned Nexststrain framework.
Results
Sixteen complete local HPV16 isolate genomes were reconstructed from WGS data of samples collected in Latvia during 2012-2023. Isolate sequences show high conservation with ≤0.36% genome divergence from the reference genome. A total of 93 non-redundant variants were identified, with previously undocumented mutations localized primarily in non-coding genomic regions. E7 protein sequences were fully conserved. Capsid proteins L1 and L2 showed the highest variability, demonstrating a cluster of characteristic amino acid (aa) substitutions. Certain substitutions observed, including S220T (E1), P219S, T310K (E2), and L90V (E6), were earlier associated to increased pathogenicity and/or cancer risk.
Conclusions
HPV16 genomes circulating in Latvia exhibit low variability. Single nucleotide polymorphisms (SNPs) observed were earlier identified in geographic regions distant from Latvia. SNPs yield aa substitutions shaping viral pathogenicity and/or antiviral immune response. These findings indicate uniform direction of HPV16 evolution, with implications for epidemiology, vaccine design, and personalized management of HPV-associated pathologies. Supported by FLPP project lzp-2021/1-0484.
| Period | 26 Mar 2025 |
|---|---|
| Event title | RSU Research week 2025: Research week 2025 |
| Event type | Conference |
| Organiser | Rīga Stradiņš University |
| Location | Rīga, LatviaShow on map |
| Degree of Recognition | International |