Genetic variation in the E6 and E7 genes of human papillomavirus type 16 in northeastern Argentina

Abstract

The province of Misiones is considered a region with a high mortality rate due to cervical cancer (CC). To gain insight into this problem, we explored the association between genetic variation in the E6 and E7 oncogenes of HPV16 and the risk of CC.We studied 160 women with cytological diagnoses of negative for intraepithelial lesion or malignity, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion/CC and a positive test for HPV16 infection. The genetic characterization of E6 and E7 genes was undertaken through PCR amplification and direct Sanger sequencing. Phylogenetic classification was conducted using Bayesian methods. To estimate the odds ratio (OR) for an association between genetic variants in the E6 and E7 genes and the risk of CC, we used ordinal logistic regression adjusted by age. The final data set comprised 112 samples. Diagnostic single-nucleotide polymorphisms (SNPs) and phylogenetic trees confirmed the presence of Lineage A (95.5%) and D (4.5%) in the samples. For the E6 gene, we identified eleven different sequences, with the most common ones being Lineage A E6 350G (58.9%) and E6 350T (37.5%). The E6 350G was associated with progression to HSIL/CC, with an OR of 19.41 (4.95-76.10). The E7 gene was more conserved than E6, probably due to the functional constraints of this small protein.Our results confirmed the association of the E6 350G SNP with a higher risk of developing CC. These data will contribute to understanding the biological bases of CC incidence in this region.

Epidemiology and Molecular Biology of HPV Variants in Cervical Cancer: The State of the Art in Mexico

“…The distribution of HPV intratype variants varies significantly in different geographical areas [ 23 , 77 , 78 , 79 ]. Nevertheless, there is accumulating evidence showing that non-European HPV-16 variants, have a higher oncogenicity due to their association with high-grade lesions of the cervix and invasive tumors [ 22 , 23 , 24 , 27 , 80 , 81 , 82 , 83 ].…”

Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer

“…Lagstrom et al found an average of 48.3 variants (range 15–82) per whole HPV16 genome in 15 Dutch women aged 16–29 years; however, the population were women from the community invited for screening [ 30 ]. A population study of 160 Argentinian women suggested that the E6 350G SNP was associated with high rates of progression to high-grade cervical disease or CC (OR 19.41 [4.95–76.10]); however, it did not include any women aged ≤25 years with CC [ 31 ]. This variant was not more common in our case population (33%) compared with controls (50%), suggesting that it did not play a significant role in causing earlier compared to later onset disease.…”

Genetic Variability in the E6/E7 Region of Human Papillomavirus 16 in Women from Ecuador

“…A study from Brazil involving 20 cases of cervical lesions (LSIL and HSIL) in HIV-negative women found a prevalence of lineage D of 15% [ 37 ]. Finally, a larger case-control study from Argentina by Totaro et al (2021) identified a frequency of lineage D of 6% among 83 samples of L-SIL/HSIL/cancer lesions [ 38 ]. Nevertheless, future studies with large sample sizes will help elucidate the epidemiology of HPV16 lineages in this population.…”