Prevalence, lineages and sublineages of human papillomavirus type 16 in background, precancerous diseases and cervical cancer in the North West of Russia

Among the highly oncogenic human papillomavirus (HPV) types, HPV 16 is of paramount importance in the pathogenesis of cervical cancer. Viral oncogenes E6 and E7, expressed by the HPV genome, play a key role in developing neoplasia. The aim was to study the prevalence, mutations in the E6–E7 genes, HPV 16 lineages and sublineages in underlying, precancerous lesions, and cervical cancer. Materials and methods. Cervical samples from 223 patients with morphologically confirmed background, precancerous diseases and cervical cancer in St. Petersburg were examined. HPV detection and genotyping were performed using real-time PCR. Sequencing of the E6–E7 genes of HPV 16 was performed using the Sanger method. Single-nucleotide polymorphisms were identified against the European lineage HPV 16 K02718 reference sequence. Results. In patients with underlying conditions, the proportion of HPV-positive samples was 55.0%. As the severity of tumor lesions progressed, the frequency of viral detection increased: from 65.0% in low-grade dysplasia to 95.1% in squamous cell carcinoma (p = 0.002). Monoinfection with HPV 16 was identified in 68.3% of patients with precancerous and malignant cervical lesions. The proportion of HPV 16 increased with the progression of neoplasia: from 38.4% in low-grade dysplasia to 77.6% in cervical cancer (p = 0.008). Sequencing of HPV 16 E6–E7 genes revealed nucleotide variations characteristic of phylogenetic lineage A. The most prevalent variant was 350G (56.3%), whose detection rate in cervical cancer exceeded that in the group without pathology — 69.8% vs 44.2% (p = 0.019). The frequency of the European variant 350T ranged from 9.7% to 35.5% depending on the degree of cervical lesion. Phylogenetic analysis revealed that 98.6% of clinical isolates belonged to lineage A, of which 74.8% were assigned to sublineage A2 of HPV 16. Sublineages A1, A2, A3, and D1 were detected in background cervical diseases, with a predominance of sublineage A2 (p = 0.001). Multiple mutations in the E6–E7 genes were detected in two isolates from imported cases, and they were assigned to sublineage D1. Only sublineages A1 and A2 of HPV 16 were detected in cervical intraepithelial neoplasia and cervical cancer. Conclusion. The study results showed that in a megacity in northwestern Russia, HPV 16 sublineage A2 plays a leading role in the etiopathogenesis of precancerous lesions and cervical cancer, with sublineage A1 also making a substantial contribution.