RESUMEN
Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non-Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are nephrotoxicity, mucositis, and myelosuppression, especially when used in high doses. The potential adverse reactions and toxicities associated with MTX are a cause for concern and may lead to dose reduction or treatment interruption. Genetic variants in MTX transport genes have been linked to toxicity. Pharmacogenetic studies conducted in the past focused on single nucleotide polymorphisms (SNPs) in the coding and 5'-regulatory regions of genes. Recent studies have demonstrated a significant role of microRNAs (miRNAs) in the transport and metabolism of drugs and in the regulation of target genes. In the last few years, the number of annotated miRNAs has continually risen, in addition to the studies of miRNA polymorphisms and MTX toxicity. Therefore, the objective of the present study is to investigate the role of miRNA variants related to MTX adverse effects.
RESUMEN
BACKGROUND: Infection with human papillomaviruses (HPVs) can cause benign and malignant tumours in the anogenital tract and the oropharynx both in men and women. The aim of the presented study was to investigate cervical, anal, and oral HPV-detection rates among women referred to colposcopy for abnormal Cervical Cancer (CaCx) screening results and assess the concordance of HPV-types among these anatomical sites. METHODS: Women referred to colposcopy at a single centre due to abnormal cytology, conducted for CaCx screening, were subjected to cervical Liquid-based Cytology (LBC) smear testing, anal and oral sampling. Routine colposcopy consisted in multiple biopsies and/or Endocervical Curettage (ECC). HPV-detection was performed by PCR genotyping in all three anatomical sites. In high-risk (hr) HPV-DNA positive samples either from anal canal or oral cavity, anal LBC cytology and anoscopy were performed, or oral cavity examination respectively. Descriptive statistics was used for the analysis of HPV-detection rates and phi-coefficient for the determination of HPV-positivity concordance between the anatomical sites. RESULTS: Out of 118 referred women, hr. HPV-DNA was detected in 65 (55.1%), 64 (54.2%) and 3 (2.5%) at cervix, anal canal and oral cavity respectively while low-risk HPV-DNA was detected in 14 (11.9%) and 11 (9.3%) at cervix and anal canal respectively. The phi-coefficient for cervix/anal canal was 0.392 for HPV16, 0.658 for HPV31, 0.758 for HPV33, - 0.12 for HPV45, 0.415 for HPV52 and 0.473 for HPV58. All values were statistically significant (p < 0.001). CONCLUSIONS: The results suggest that most HPV-types, high-risk and low-risk, detected in the cervix of women with prevalent cervical dysplasia, correlate with the ones detected in their anal canal. This particularly applies for the HPV-types included in the nonavalent HPV-vaccine (HPVs 6/11/16/18/31/33/45/52/58).