Variantes e mutações do HPV 16 e o perfil clínico e histopatológico de mulheres amazônidas com câncer de colo do útero

Abstract

HPV 16, considered one of the most important human carcinogens, is the prevalent genotype in the world, with an occurrence rate of 15.3%. It can be divided into four lineages (A, B, C, D) and at least sixteen sublineages; these confer different risks for the development of pre-cancer and cancer. In this context, studies on variants circulating in the Amazon region are still scarce. Therefore, this study sought to describe the circulating variants and mutations of HPV16 in Amazonian women with cervical cancer and relate them to the clinical and pathological characteristics of the patients. The study included women diagnosed with cervical cancer who arrived for treatment at FCECON. HPV16 59 samples positive were sequenced through next generation sequencing using a protocol modified. FASTQ readings were analyzed using the Genious Prime program; and sequence quality parameters were analyzed. 33 samples were included following the quality criteria proposed in the study. Were included 33 samples following the quality criteria proposed in the study. According to the clinical characteristics of the patients, the majority – 27.2% – were between 46 and 55 years old; around 6.0% were under 25 years of age; These two patients were 20 years old at the time of sample collection. Regarding race, 90.9% declared themselves white; and 84.8% were from the interior of the State of Amazonas. The most common histological type was squamous cell carcinoma, with 72.5%, followed by 27.5% of adenocarcinoma. The FIGO staging, which ranged from IB to IVB, was heterogeneous, and the most common was IB1 (18.1%). Of the 33 patients in the study, five (15.2%) died due to the disease (CID539). Regarding the prognosis, 60.6% were considered to have advanced disease. Lineage A was found most frequently (51.6%), followed by lineage D (41.9%), C and B (3.2% for each of them). Only sublineages A1, B1, C1 and D3 were found. The A1 sublineage was found in 16 samples, with 51.6%; the D3 sublineage was the second most common, with 41.9%; sublineages B1 and C1 were found – each in a different sample. The mutations were classified as being 55.4% synonymous/silent; and 44.6% missense/non-silent mutations. Among the most frequent missense mutations, the following stand out: A3115C (I44L) isoleucine>leucine; A5570G (T266A) threonine>alanine; and A3178G (I65V) isoleucine>valine – found in 60.6% of the samples analyzed –, in addition to the A4362C (L330F) leucine>phenylalanine mutation (57.6%). In conclusion, the data presents information on the diversity of variants, as well as the SNPs and missense mutations found in the HPV 16 genome and the use of the complete sequencing methodology of the HPV 16 genome by next generation sequencing (NGS) allowed, on a large scale, identify characteristics in the intratypic variability of HPV 16, which perhaps, using other methodologies, could go unnoticed, which in the future can be used in future studies related to the pathogenesis of the disease and HPV16 in this region.