RESUMO
Cervical carcinoma is the second most common malignancy among women in both incidence and mortality. Although much is known about the etiology and treatment of cervical cancer, the role of genetic alterations in the multistep pathway of cervical tumorigenesis is largely unknown. The aim of this study was to characterize the genomic changes in the cervical pre-cancerous lesions and tumors, induced by different types of human papillomaviruses. In this research was used the BlueGnome CytoChip oligo 2 × 105 K microarray for whole-genome oligo-array CGH. Microarray CGH analysis of 40 specimens was carried out-12 specimens from patients with early-stage squamous cell carcinomas; 19 specimens from patients with mild to moderate dysplasia and 9 with severe dysplasia. First we performed microarray CGH analysis of five DNA pools which contained the DNA from homogeneous groups of patients. The results revealed presence of micro chromosomal aberrations in chromosome region 14q11.2. According to the genome database these aberrations represent polymorphisms. Microarray analysis of DNA from 9 separate carcinoma lesions revealed a total of 26 aberrations in 14 chromosomes of nine patients. Our results showed the advantages of high-resolution chips in the clinical diagnosis of patients with cancerous and precancerous lesions caused by viral infection with HPV, but also highlight the need for extensive population studies revealing the molecular nature and clinical significance of different CNVs and the creation of detailed maps of variations in the Bulgarian population. This would facilitate extremely precise interpretation of specific genomic imbalances in the clinical aspect.
RESUMO
Human papillomavirus (HPV) is a well-known pathogen for lower genital tract neoplasias, yet little is known regarding HPV prevalence in Bulgaria. The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among women with normal and abnormal cytology. Cervical smears with different cytological diagnoses were collected from 355 Bulgarian patients. The cohort of patients selected is the biggest ever studied in this country. Using the Roche Linear Array HPV Genotyping Test, papillomavirus DNA was found in 217 out of the 355 samples, 164 of which had only one and 53 had more than one HPV type. The distribution of the viruses tested in 355 samples was as follows: (i) the most common type was HPV 16, which was found in 61 samples; (ii) the next most frequent HPV type was HPV 33, found in 14 of the samples. A high prevalence of HPV infection was observed in this study. As HPV infection has a high correlation with cervical cancer, this study emphasizes the need for both primary prevention of cervical cancer with HPV vaccines as well as secondary prevention with screening. Currently, two HPV vaccines are included in the National immunization schedule in Bulgaria. Thus, new clinical studies will benefit from patient stratification by the presence or absence of HPV, and by designing separate clinical trials specifically for HPV associated cancers.
