The human papillomavirus (HPV)-related cancer biology: An overview.

Despite the novel diagnostic methods and therapies implemented in oncology, the number of patients that succumb by the cancer remains high globally. Currently studies point out that 20-25% of all human malignancies are related to micro-organism infections. Among these cancer-related pathogens, the human papillomavirus (HPV) has a prominent position, since the virus is responsible for about 30% of all infectious agent-related cancers. Thus, an amount of cancers could be avoided by means prophylactic and/or therapeutic measures. However, these measures required a holistic comprehension about HPV-related cancer biology. Based on this, this review aims to summarize the last evidences of HPV on cancer biology (from initiation to metastasis), focus on molecular and biochemical deregulations associated with viral infection, and discuss the viral etiology in different malignancies.

The human papillomavirus (HPV)-related cancer biology: an overview

Despite the novel diagnostic methods and therapies implemented in oncology, the number of patients that succumb by the cancer remains high globally. Currently studies point out that 20–25% of all human malignancies are related to micro-organism infections. Among these cancer-related pathogens, the human papillomavirus (HPV) has a prominent position, since the virus is responsible for about 30% of all infectious agent-related cancers. Thus, an amount of cancers could be avoided by means prophylactic and/or therapeutic measures. However, these measures required a holistic comprehension about HPV-related cancer biology. Based on this, this review aims to summarize the last evidences of HPV on cancer biology (from initiation to metastasis), focus on molecular and biochemical deregulations associated with viral infection, and discuss the viral etiology in different malignancies.

The human papillomavirus (HPV)-related cancer biology: an overview

Despite the novel diagnostic methods and therapies implemented in oncology, the number of patients that succumb by the cancer remains high globally. Currently studies point out that 20–25% of all human malignancies are related to micro-organism infections. Among these cancer-related pathogens, the human papillomavirus (HPV) has a prominent position, since the virus is responsible for about 30% of all infectious agent-related cancers. Thus, an amount of cancers could be avoided by means prophylactic and/or therapeutic measures. However, these measures required a holistic comprehension about HPV-related cancer biology. Based on this, this review aims to summarize the last evidences of HPV on cancer biology (from initiation to metastasis), focus on molecular and biochemical deregulations associated with viral infection, and discuss the viral etiology in different malignancies.

Tyms double (2R) and triple repeat (3R) confers risk for human oral squamous cell carcinoma.

The oral cancer is responsible for approximately 3 % of cases of cancer in Brazil. Epidemiological studies have associated low folate intake with an increased risk of epithelial cancers, including oral cancer. Folic acid has a key role in DNA synthesis, repair, methylation and this is the basis of explanations for a putative role for folic acid in cancer prevention. The role of folic acid in carcinogenesis may be modulated by polymorphism C677T in MTHFR and tandem repeats 2R/3R in the promoter site of TYMS gene that are related to decreased enzymatic activity and quantity and availability of the enzyme, respectively. These events cause a decrease in the synthesis, repair and DNA methylation, which can lead to a disruption in the expression of tumor suppressor genes as TP53. The objective of this study was investigate the distribution of polymorphisms C677T and tandem repeats 2R/3R associated with the development of oral squamous cell carcinoma (OSCC). 53 paraffin-embedded samples from patients who underwent surgery but are no longer at the institution and 43 samples collected by method of oral exfoliation by cytobrush were selected. 132 healthy subjects were selected by specialists at the dental clinics of the Faculdade de Odontologia de Pernambuco-FOP. The MTHFR genotyping was performed by PCR-RFLP, and the TYMS genotyping was performed by conventional PCR. Fisher's Exact test at significant level of 5 %. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to measure the strength of association between genotype frequency and OSCC development. The results were statistically significant for the tandem repeats of the TYMS gene (p = 0.015). The TYMS 2R3R genotype was significantly associated with the development of OSCC (OR = 3.582; 95 % CI 1.240-10.348; p = 0.0262) and also the genotype 3R3R (OR = 3.553; 95 % CI 1.293-9.760; p = 0.0345). When analyzed together, the TYMS 2R3R + 3R3R genotypes also showed association (OR = 3.518; 95 % CI 11.188-10.348; p = 0.0177). No differences for the MTHFR C677T polymorphisms distribution were found between the oral cancer patients and controls subjects in our study (p = 0.499). Therefore, these data suggest that determination of TYMS tandem repeats could provide information on the comprehension of the risk factors and prevention of the OSCC.

Polymorphisms involved in folate metabolism pathways and the risk of the development of childhood acute leukemia.

OBJECTIVE: Polymorphisms that reduce the activity of reduced folate carrier (RFC) and methylenetetrahydrofolate reductase (MTHFR) and double (2R2R) or triple (3R3R) 28-bp tandem repeats in the promoter region of thymidylate synthase (TS) have been associated with the risk of childhood acute leukemia (AL). A case-control genotyping study was conducted in Brazilian children with the aim of investigating RFC, MTHFR, and TS polymorphisms as risk factors. METHODS: The polymerase chain reaction-restriction fragment length polymorphism method was employed in 177 AL cases and 390 controls. RESULTS: The presence of the mutant 1298C, also RFC 80A, was linked to a decreased risk of developing acute lymphoid leukemia (ALL) (odds ratio (OR)=0.46, 95% confidence interval (CI)=0.30-071 and OR=0.51, 95% CI=0.28-0.0.93, respectively). CONCLUSIONS: The genotype 677 CT was associated with increased risk of developing ALL (OR=1.6, 95% CI=1.1-2.7). Further epidemiological study is needed to unravel the role of complex multiple gene-environment interactions in leukemogenesis.

Identificação do Papilomavirus Humano em mucosa oral de mulheres portadoras do vírus em cérvice uterina atendidas em hospital de referência em oncologia / Identification of Human Papillomavirus in oral mucosa of women which has the viral infection in uterine cervix attended at a referral hospital in oncology

Introduction: Oral cancer is one of the most common types of cancer worldwide, makingit necessary to know the risk factors related to this disease. Although there is a wellestablished association with other risk factors, studies developed so far do not allow todefine precisely the role of Human Papillomavirus in oral carcinogenesis. Objective -Investigate the presence of Human Papillomavirus in oral mucosa of women with HumanPapillomavirus in the uterine cervix. Material and Methods - The analysis includedsamples of 47 women aged 21 to 62 years old. The biological material was obtained byexfoliative cytology (cytobrush) of oral mucosa, and tested by Polymerase Chain Reactionfor identification of HPV. Results - The results showed cytopathological interpretation,light microscopy, 5/47 (10.63%) with changes indicative of Human Papillomavirus. Inlaboratory tests 8/47 (17, 02%) of the collections of buccal swabs were positive for HumanPapillomavirus-DNA. Conclusion - The Human Papillomavirus detection by PCRtechnique was more sensitive in identifying the Human Papillomavirus in oral mucosa.This study does not allow a definitive conclusion about the relationship of HPV in thecervix and oral mucosa.

Introdução: O câncer de boca é um dos tipos mais comuns de câncer no mundo, tornando-se necessário o conhecimento dos fatores de risco relacionados a essa doença. Apesar deexistir uma associação bem estabelecida com outros fatores de risco, os estudos desenvolvidosaté hoje não permitem definir com precisão qual o papel do HPV na carcinogêneseoral. Objetivo: Investigar a presença do HPV na mucosa oral de mulheres portadoras deHPV na cérvice uterina. Material e Método - Foram analisadas amostras de 47 mulheresna faixa etária de 21 até 62 anos de idade. O material biológico foi obtido por citologiaesfoliativa (cytobrush) da mucosa oral, e testado para identificação do HPV através datécnica de PCR. Resultados - Os resultados apontaram na interpretação citopatológica,à microscopia óptica, 5/47 (10.63%) com alterações indicativas de HPV. Nos testeslaboratoriais (PCR) 8/47 (17,02%) das coletas dos esfregaços bucais apresentaram-sepositivas para o HPV-DNA. Conclusões - A detecção do HPV pela técnica de PCR mostrouser mais sensível na identificação do HPV na mucosa oral. Esse estudo não permite umaconclusão definitiva sobre a relação entre o HPV na cérvice uterina e na mucosa oral.