Exploring Human Papillomavirus 16 Long Control Region Variants in Paraguayan Women: Comparing Variant Diversity to...

Human papillomavirus Type 16 (HPV16) variants are classified into four lineages (A-D) and 16 sublineages: A1-3 (European), A4 (Asian), B1-4 and C1-4 (African), and D1-4 (Asian-American). This study investigated the genetic HPV16 variability through sequencing of the complete long control region (LCR), in 44 cervical samples from Paraguayan women, including 19 without cervical intraepithelial neoplasia grade 2 (p < 0.05), although none remained statistically significant after correction for multiple comparisons. Notably, most of these mutations were predominantly observed in non-A1-A3 variants. An exploratory association was observed between non-A1-A3 variants and the presence of CIN2+ ( p = 0.0065). Functional analysis revealed that the A4 variant, detected in a woman with cancer, exhibited the highest transcriptional activity (2.34 ± 0.78), followed by D3 (0.72 ± 0.21) and A1 (0.03 ± 0.02), corresponding to samples from women with CIN3 and without lesions, respectively. In conclusion, we report for the first time the detection of an A4 HPV16 variant in Paraguay, which exhibited the highest transcriptional activity among the variants analyzed. These findings suggest potential functional differences among HPV16 variants and are consistent with a possible relevance of non-A1-A3 variants in cervical lesion severity. However, these results should be interpreted with caution as exploratory and hypothesis-generating.