Human Papillomavirus Type 16 L2 Gene Sequence Variation Analysis in Indonesian Cervical Cancer Specimens

Abstract

Background: Human papillomavirus type 16 (HPV16) is the most common etiological cause of cervical cancer in Indonesian women. HPV16 L2 genetic variation analysis is important for vaccine strategies of cervical cancer, yet the data in Indonesia is still limited. In this research, we determined the variation of the HPV16 L2 gene sequences in Indonesian cervical cancer specimens. Method: We cross-sectionally observed a total of 23 DNA isolates of HPV16 positive specimens stored in the laboratory of the Center for Diagnostic and Research on Infectious Diseases (PDRPI Lab) Faculty of Medicine, Universitas Andalas, Padang, Indonesia. The HPV16 L2 genes were amplified, sequenced, and followed by DNA alignment, single nucleotide polymorphisms (SNPs) analysis, and phylogenetic tree reconstruction. Results: As many as 35 SNPs were found, consist of 18 synonymous SNPs (sSNPs) and 17 non-synonymous SNPs (nsSNPs). Amino acid variations were mostly detected at S269P (100%) and L330F (43.48%) with no variation in the immuno-protective region near L2 N-terminus. A total of 5 HPV16 phylogenetic sub-lineages were found closely related to A1 (n=5), A2 (n=12), A3 (n=2), A4 (n=3), and C (n=1). Conclusion: The variation of HPV16 L2 gene sequences was mostly located on the central region of the L2 sequences and the cross-protective region near the L2 N-terminus was particularly conserved. This study should enhance the information about HPV16 L2 gene variation in Indonesia.

Longitudinal follow‐up of HPV16 sequence after cervical infection: Low intrahost variation and no correlation with clinical evolution

“…Since this mutation is located in the central region of the sequence, far from the important DNA binding domains, the furin cleavage site, and the identified neutralizing epitope regions (all located at the N‐terminal part of the protein), its biological relevance is unclear. The prevalence of this mutation among HPV16 sequences from different lineages is unknown but its presence has been recently observed in 43.5% of HPV16‐positive specimens, mainly classified in lineage A, for which the L2 sequence variations were investigated 21 . While the clinical impact of this mutation was not explored in this latter study, a previous case report had identified this mutation in all HPV16 sequences obtained after the microdissection of a cervical invasive squamous cell carcinoma coexisting with multiple CIN2 and CIN3 lesions in a unique patient 22 .…”