vitamin-b-12 and Papillomavirus-Infections

In the process of progression to cancer from atypical squamous cells of undetermined significance (ASCUS), mostly Human Papilloma Virus (HPV) is responsible. Additionally, patients with cell cycle disorders are thought to be at risk. The aim of this prospective cohort trial was to analyze the association between presence of ASCUS and HPV persistence with folate and vitamin B12 levels. 200 patients who had Papanicolaou (PAP) smear test were divided into a ASCUS group (n:100) and control group (n:100). Control group consisted of women who did not have intraepithelial neoplasia, based on PAP smear results. HPV testing was also done in study group. Serum vitamin B12 and folate levels in ASCUS (+) HPV (+) patients were significantly lower than that of ASCUS (-) or ASCUS (+) HPV (-) patients (

Topics: Alphapapillomavirus; Atypical Squamous Cells of the Cervix; DNA, Viral; Female; Folic Acid; Humans; Papillomaviridae; Papillomavirus Infections; Prospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin B 12

The human papilloma virus (HPV) is the etiological agent of cervical cancer in more than 95% of cases worldwide. Although most HPV infections clear up on their own and most pre-cancerous lesions spontaneously resolve, in some cases, they can persist, leading to lesions which may progress towards invasive cervical cancer.. We evaluated the effects of the association of epigallocatechin gallate (EGCG) + folic acid (FA) + vitamin B12 (B12) + hyaluronic acid (HA) on HPV-positive cervical cancer cells (HeLa).. The association of EGCG + FA + B12 + HA induced a significant increase of apoptosis and p53 gene expression with a concomitant decrease of E6/E7 gene expression, a marker of HPV infection.. This study provides for the first-time evidence on the potential additive activity of EGCG + FA + B12 + HA in counteracting HPV infection, by increasing apoptosis and p53 expression in HPV-infected cervical HeLa cells.

Topics: Apoptosis; Female; Folic Acid; HeLa Cells; Humans; Hyaluronic Acid; Papillomavirus Infections; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms; Vitamin B 12

Elevated succinyl-CoA and cobalamin levels were associated with high-grade squamous intraepithelial lesions.

Topics: Anus Neoplasms; Biomarkers; Carcinoma, Squamous Cell; Early Detection of Cancer; Humans; Papillomavirus Infections; Vitamin B 12

To analyze the association of cervical cytological abnormalities with genetic polymorphisms of enzymes involved in folate metabolism, and the effect of micronutrients on association of polymorphisms with cervical carcinogenesis. Our samples were divided in Control (120 women with normal cytology), and Cases: 37 women with Atypical Squamous Cells of Undetermined Significance(ASC-US), 33 participants presenting Low-Grade Squamous Intraepithelial Lesion(LSIL), and 24 women presenting High-Grade cervical lesions(HSIL/ASC-H). We obtained cervical samples for cytological analysis, HPV detection, and analysis of polymorphisms and cervical cell folate. Blood samples were obtained for serum folate and vitamin B12 evaluation. To analyze all polymorphisms simultaneously, we calculated Genetic Risk Score(GRS). Median concentrations were used as cutoff for determination of micronutrient levels. We observed no differences of genotype or allelic frequencies of polymorphisms according to cervical lesions. However, high levels of cervical cell folate and high number of genetic alterations increased risk of High-Grade lesions [OR(IC95%):1.85(0.42-8.11)]. Instead, women with vitamin B12 ≤ 274 pg/ml and GRS ≥ 3 presented even greater risk of HSIL/ASC-H [OR(IC95%):2.91(0.46-18.62)]. High frequency of genetic polymorphisms involved in one-carbon metabolism associated with high levels of cell folate or low levels of serum vitamin B12, increased the risk of High-Grade lesion in uterine cervix.

Topics: Carbon; Female; Folic Acid; Humans; Papillomaviridae; Papillomavirus Infections; Polymorphism, Genetic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin B 12

Human papillomavirus (HPV) infection is a common sexually transmitted disease. Although often transitory, persistent oncogenic HPV infection may progress to a precursor lesion and, if not treated, can further increase the risk of cancer. The purpose of this study was to investigate the relation between dietary intake and HPV persistent infection in men of a Brazilian cohort. The study population consisted of 1,248 men from the Brazilian cohort of the HIM (HPV in Men) Study, ages 18 to 70 years, who completed a quantitative food frequency questionnaire. U Mann-Whitney test was used to assess differences in median nutrient intake of selected nutrients. The association of dietary intake and persistent HPV infection was assessed in multivariate logistic models. The prevalence of any HPV infection at baseline was 66.6%. Of 1,248 participants analyzed, 1,211 (97.0%) were HPV positive at one or more times during the 4 years of follow-up and 781 (62.6%) were persistently HPV positive. Men with nonpersistent oncogenic HPV infections had higher median intake of retinol (p = 0.008), vitamin A (p < 0.001) and folate (DFE; p = 0.003) and lower median intake of energy (p = 0.005) and lycopene (p = 0.008) in comparison to men with persistent oncogenic infections. No significant association was found between selected nutrients and persistent oncogenic HPV infection. For nononcogenic persistent infections, only vitamin B12 intake was significantly associated (p = 0.003, test for trend). No association was observed between dietary intake and persistent oncogenic-type HPV infection; however, vitamin B12 intake was inversely associated with nononcogenic HPV persistence.

Topics: Adult; Aged; Alphapapillomavirus; Brazil; Carotenoids; Diet; Feeding Behavior; Folic Acid; Humans; Logistic Models; Lycopene; Male; Middle Aged; Nutrition Surveys; Papillomavirus Infections; Prospective Studies; Vitamin A; Vitamin B 12; Young Adult

Most cases of cervical cancer are associated with human papilloma virus (HPV) infection of high risk types. In folate deficiency, heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) interferes with HPV16 viral capsid protein synthesis. We aimed to study the importance of 1-carbon metabolism in cervical carcinogenesis by examining serum vitamin B12 (cobalamin), homocysteine, folate levels, and the RNA and protein expression of HPV16 L1, L2, E6, E7, and to correlate them with hnRNP-E1 expression and HPV infection in normals, squamous intraepithelial lesions (SILs), and cervical cancer subjects. Serum cobalamin, folate, and homocysteine were estimated using kits, RNA by real time PCR and proteins by Western blotting. We observed that lower folate and vitamin B12 levels were associated with HPV infection. hnRNP-E1 progressively decreased from normals (100%) to SILs (75%) to cervical cancer (52.6%). The findings show that HPV16 E6 and E7 are overexpresed whereas HPV16 L1 and L2 are downregulated at mRNA and protein levels in cervical cancer as compared to normals and SILs. The results indicate that perhaps the reduced expression of hnRNP-E1 might be involved with the cervical cancer pathogenesis, with folate playing a role in the natural history of HPV infection.

Topics: Adult; Aged; DNA-Binding Proteins; Down-Regulation; Female; Folic Acid; Heterogeneous-Nuclear Ribonucleoproteins; Homocysteine; Humans; Middle Aged; Oncogene Proteins, Viral; Papillomavirus Infections; Repressor Proteins; Risk Factors; RNA-Binding Proteins; RNA, Messenger; Squamous Intraepithelial Lesions of the Cervix; Uterine Cervical Neoplasms; Viral Proteins; Vitamin B 12

We previously reported that a higher degree of methylation of CpG sites in the promoter (positions 31, 37, 43, 52, and 58) and enhancer site 7862 of human papillomavirus (HPV) 16 was associated with a lower likelihood of being diagnosed with HPV 16-associated CIN 2+. The purpose of this study was to replicate our previous findings and, in addition, to evaluate the influence of plasma concentrations of folate and vitamin B12 on the degree of HPV 16 methylation (HPV 16m). The study included 315 HPV 16-positive women diagnosed with either CIN 2+ or ≤CIN 1. Pyrosequencing technology was used to quantify the degree of HPV 16m. We reproduced the previously reported inverse association between HPV 16m and risk of being diagnosed with CIN 2+. In addition, we observed that women with higher plasma folate and HPV 16m or those with higher plasma vitamin B12 and HPV 16m were 75% (P < 0.01) and 60% (P = 0.02) less likely to be diagnosed with CIN 2+, respectively. With a tertile increase in the plasma folate or vitamin B12, there was a 50% (P = 0.03) and 40% (P = 0.07) increase in the odds of having a higher degree of HPV 16m, respectively. This study provides initial evidence that methyl donor micronutrients, folate and vitamin B12, may play an important role in maintaining a desirably high degree of methylation at specific CpG sites in the HPV E6 promoter and enhancer that are associated with the likelihood of being diagnosed with CIN 2+.

Topics: Adult; Biopsy; CpG Islands; DNA Methylation; DNA, Viral; Enhancer Elements, Genetic; Female; Folic Acid; Genotype; Human papillomavirus 16; Humans; Male; Micronutrients; Middle Aged; Oncogene Proteins, Viral; Papillomavirus Infections; Promoter Regions, Genetic; Repressor Proteins; Risk Factors; Sequence Analysis, DNA; Uterine Cervical Dysplasia; Vitamin B 12; Young Adult

Cervical cancer is the most common cancer among women in India and a leading cause of death in these women. Most cases of cervical cancer are associated with human papillomavirus (HPV) infection of the high-risk type. It has been reported that aberrant DNA methylation can be associated with HPV infection and cervical cancer, and folate is directly involved in DNA methylation via one-carbon metabolism. We aimed to study the importance of one-carbon metabolism in the progression of cervical carcinogenesis by examining serum levels of vitamin B(12) (cobalamin), homocysteine, and folate and DNA methylation of tumor suppressor genes CDH1, HIC1, and Retinoic acid receptor beta (RARβ) amid these women ranging from normal to squamous intraepithelial neoplastic lesions (SIL) to cervical cancer. Blood and tissue samples were collected from normal (n = 35), SILs (n = 27), and cervical cancer patients (n = 38) in the age group of 26-70 years. Measurement of serum vitamin B(12), folate, and homocysteine were done using kits (Immulite). Promoter methylation was examined using methylation-specific PCR. The frequency of promoter hypermethylation for all the three tumor suppressor genes CDH1, HIC1, and RARβ showed an increasing trend from normal to dysplastic to invasive cervical cancer (p < 0.05). We observed that lower folate and vitamin B(12) status were associated with HPV infection. Taken together, our findings suggest a role of folate and vitamin B(12) in modulating the risk of cervical cancer and HPV infection. CDH1, HIC1, and RARβ genes can be used as potential biomarkers of cervical cancer risk assessment.

Topics: Adult; Aged; Antigens, CD; Cadherins; Carbon; DNA Methylation; Female; Folic Acid; Genotype; Homocysteine; Humans; Kruppel-Like Transcription Factors; Middle Aged; Papillomaviridae; Papillomavirus Infections; Receptors, Retinoic Acid; Uterine Cervical Neoplasms; Vitamin B 12

The objective of the study was to evaluate LINE-1 methylation as an intermediate biomarker for the effect of folate and vitamin B12 on the occurrence of higher grades of cervical intraepithelial neoplasia (CIN ≥ 2).. This study included 376 women who tested positive for high-risk human papillomaviruses and were diagnosed with CIN ≥ 2 (cases) or CIN ≤ 1 (non-cases). CIN ≥ 2 (yes/no) was the dependent variable in logistic regression models that specified the degree of LINE-1 methylation of peripheral blood mononuclear cells (PBMCs) and of exfoliated cervical cells (CCs) as the independent predictors of primary interest. In analyses restricted to non-cases, PBMC LINE-1 methylation (≥ 70% versus <70%) and CC LINE-1 methylation (≥ 54% versus <54%) were the dependent variables in logistic regression models that specified the circulating concentrations of folate and vitamin B12 as the primary independent predictors.. Women in the highest tertile of PBMC LINE-1 methylation had 56% lower odds of being diagnosed with CIN ≥ 2 (odds ratio 0.44, 95% confidence interval 0.24-0.83, P = 0.011), whereas there was no significant association between degree of CC LINE-1 methylation and CIN ≥ 2 (odds ratio 0.86, 95% confidence interval 0.51-1.46, P = 0.578). Among non-cases, women with supraphysiologic concentrations of folate (>19.8 ng/mL) and sufficient concentrations of plasma vitamin B12 (≥ 200.6 ng/mL) were significantly more likely to have highly methylated PBMCs compared with women with lower folate and lower vitamin B12 (odds ratio 3.92, 95% confidence interval 1.06-14.52, P = 0.041). None of the variables including folate and vitamin B12 were significantly associated with CC LINE-1 methylation.. These results suggest that a higher degree of LINE-1 methylation in PBMCs, a one-carbon nutrient-related epigenetic alteration, is associated with a lower risk of developing CIN.

Topics: Adult; Biomarkers; Carbon; Case-Control Studies; Cervix Uteri; Confidence Intervals; Deoxyribonuclease I; DNA Methylation; Epigenomics; Female; Folic Acid; Follow-Up Studies; Humans; Leukocytes, Mononuclear; Logistic Models; Methylation; Middle Aged; Odds Ratio; Papillomavirus Infections; Premenopause; Promoter Regions, Genetic; Prospective Studies; Risk Factors; Surveys and Questionnaires; Uterine Cervical Dysplasia; Vitamin B 12; Vitamin B Complex; Young Adult

Human papillomavirus (HPV) infections are the cause of most, if not all, cervical cancers. Women consistently positive for oncogenic type HPV infections have a greater risk of developing cervical dysplasia compared with women transiently infected. HPV infection alone appears to be insufficient to produce disease, suggesting that other cofactors may be needed. Folate, vitamin B12, and homocysteine, through their role in DNA methylation, may be involved in cervical neoplasia.. This study examined the associations between HPV persistence and circulating folate, vitamin B12, and homocysteine levels among 91 low-income Hispanic women. Further, the relation of these nutrients to cervical pathology was evaluated. HPV status was determined at two visits approximately 3 mo apart.. Adjusted mean circulating concentrations of folate, vitamin B12, and homocysteine were not statistically different between women with two positive HPV tests, one positive test, or two negative HPV tests. No association was observed between tertiles of folate, vitamin B12, or homocysteine and HPV persistence risk. Further, adjusted mean levels of these nutrients were not statistically different between cytologic grades.. Results from this small study did not support a role for folate, vitamin B12, or homocysteine in HPV persistence or cervical dysplasia.

Topics: Adolescent; Adult; Cervix Uteri; DNA, Viral; Female; Folic Acid; Homocysteine; Humans; Nutritional Status; Papillomaviridae; Papillomavirus Infections; Tumor Virus Infections; Uterine Cervical Dysplasia; Vitamin B 12

Data have suggested that higher levels of nutrients are protective against HPV persistence and cervical neoplasia. This study assessed the role of circulating nutrients on clearance of oncogenic HPV infections.. Women were followed prospectively with visits at baseline and approximately 4- and 10-months post-baseline. At each visit, 15 oncogenic HPV types were determined. Plasma levels were assessed at the 4-month visit for retinol, carotenoids (i.e., alpha-, trans-beta-, cis-beta-carotene, alpha-, beta-cryptoxanthin, lutein, zeaxanthin, trans- and cis-lycopene), tocopherols (i.e., alpha-, delta-, and gamma-tocopherol), folate and vitamin B12. Using multivariate Cox proportional hazards models, time to clearance analyses of oncogenic HPV infections were conducted for 84 women with at least one oncogenic infection at baseline. Hazard ratios (HR) were estimated for the association of HPV clearance to each nutrient tertile and to determine linear trends.. The likelihood of clearing an oncogenic HPV infection was significantly higher with increasing levels of trans-lycopene (p for trend, 0.025) and cis-lycopene (p for trend, 0.010). The adjusted hazard ratios of the highest tertiles of trans- and cis-lycopene were 2.79 (95% CI = 1.17-6.66) and 2.92 (95% CI = 1.28-6.63) compared with the lowest tertiles.. Higher concentrations of trans- and cis-lycopene may reduce the time to clearance of an oncogenic HPV infection.

Topics: Adolescent; Adult; Carotenoids; Female; Humans; Micronutrients; Nutrition Assessment; Odds Ratio; Papillomaviridae; Papillomavirus Infections; Proportional Hazards Models; Prospective Studies; Tocopherols; Tumor Virus Infections; Viral Load; Vitamin A; Vitamin B 12

Topics: Condylomata Acuminata; Contraceptives, Oral; Female; Folic Acid; Humans; Papillomavirus Infections; Risk Factors; Smoking; Students; Vitamin B 12

Persistent oncogenic human papillomavirus (HPV) infection is associated with cervical dysplasia. Cofactors, such as nutrient status, may be required for the progression of HPV infection to neoplasia. HPV DNA methylation patterns in vitro have been shown to be associated with viral transcriptional activity. Folate, vitamin B12, vitamin B6, and methionine may function to prevent cervical cancer through their role in DNA methylation. This study was conducted to examine the relationship of dietary intake of folate, vitamin B12, vitamin B6, and methionine, as well as circulating levels of folate and vitamin B12 to HPV persistence. Oncogenic HPV status was determined at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the adjusted odds ratios for persistent HPV infection associated with each tertile of individual nutrient among 201 women with a persistent or intermittent HPV infection. Circulating vitamin B12 levels were inversely associated with HPV persistence (P for trend, 0.037) after adjusting for age, age at first intercourse, marital status, cigarette smoking status, race, and body mass index. In addition, women with circulating levels in the highest tertile (>493.2 pg/ml) of vitamin B12 were less likely to have a persistent infection (adjusted odds ratio = 0.4; 95% confidence interval = 0.17-0.96). No significant associations were observed between HPV persistence and dietary intake of folate, vitamin B12, vitamin B6, or methionine from food alone or from food and supplements combined or from circulating folate. These data suggest a role for circulating vitamin B12 in early cervical carcinogenesis.

Topics: Adolescent; Adult; Cell Transformation, Neoplastic; Cohort Studies; DNA Methylation; DNA, Viral; Female; Humans; Nutritional Status; Odds Ratio; Papillomaviridae; Papillomavirus Infections; Regression Analysis; Tumor Virus Infections; Uterine Cervical Neoplasms; Vitamin B 12

To explore the relationship between serum homocysteine, a sensitive biomarker for folate inadequacy and problems in one-carbon metabolism, and invasive cervical cancer.. A large case-control study was conducted in five US areas with up to two community controls, obtained by random-digit dialing, individually matched to each case. Cervical cancer risk factors were assessed through at-home interview. Blood was drawn at least 6 months after completion of cancer treatment from 51% and 68% of interviewed cases and controls. Serum homocysteine was measured by high-performance liquid chromatography, and exposure to human papillomavirus (HPV) type 16, the most prevalent oncogenic type, was assessed using an enzyme-linked immunosorbent assay. Cases with advanced cancer and/or receiving chemotherapy were excluded, leaving 183 cases and 540 controls.. Invasive cervical cancer risk was substantially elevated for women in the upper three homocysteine quartiles (> 6.31 micromol/L); multivariate-adjusted odds ratios ranged from 2.4 to 3.2 (all 95% CIs excluded 1.0). A trend was apparent and significant (p = 0.01). When cases were compared with HPV-16 seropositive controls only, odds ratios were comparable.. Serum homocysteine was strongly and significantly predictive of invasive cervical cancer risk. This association could reflect folate, B12 and/or B6 inadequacy, or genetic polymorphisms affecting one-carbon metabolism.

Topics: Adult; Alabama; Case-Control Studies; Chromatography, High Pressure Liquid; Colorado; Enzyme-Linked Immunosorbent Assay; Female; Florida; Homocysteine; Humans; Illinois; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Odds Ratio; Papillomaviridae; Papillomavirus Infections; Pennsylvania; Predictive Value of Tests; Regression Analysis; Risk Assessment; Risk Factors; Tumor Virus Infections; Uterine Cervical Neoplasms; Vitamin B 12; Vitamin B 6

An association between B-complex vitamins and related compounds with the development of cervical neoplasia is biologically plausible, yet to the authors' knowledge epidemiologic investigations of these potential biomarkers are limited.. A case-control study was designed to examine the relation between plasma folate, homocysteine, vitamin B(12), and cysteine and early, premalignant changes in cervical epithelial cells among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. Fasting blood samples for plasma nutrient analysis, cervical smears for cytologic diagnosis, exfoliated cervical cells for human papillomavirus DNA testing by polymerase chain reaction, and a personal interview were obtained from 185 women with atypical squamous cells of undetermined significance (ASCUS) of the cervix, 147 women with squamous intraepithelial lesions (SIL), and 191 women with cytologically normal (Papanicolaou) smears.. Age-adjusted and ethnicity-adjusted mean plasma concentrations of cysteine, but not other nutrients, were significantly lower among ASCUS cases (P = 0.006) and SIL cases (P = 0.01) than controls. A positive trend in the odds ratio for SIL but not ASCUS was found for increased plasma homocysteine concentrations, but this finding was not statistically significant. High plasma levels of cysteine were associated with a reduced risk of ASCUS (P value for trend = 0.006), with an odds ratio of 0.3 (95% confidence interval, 0.2-0.7) for the highest compared with the lowest quartile of cysteine concentration. A weak, negative relation between cysteine and the development of low grade SIL (LSIL) but not high grade SIL (HSIL) also was found.. The results of the current study do not support the hypothesis that folate, homocysteine, or B(12) are markers of cervical dysplasia risk. A possible inverse association between plasma cysteine concentrations and the risk of cervical dysplasia needs further study.

Topics: Adult; Alcohol Drinking; Case-Control Studies; Contraceptives, Oral; Cysteine; DNA, Viral; Female; Folic Acid; Gravidity; Homocysteine; Humans; Middle Aged; Papillomaviridae; Papillomavirus Infections; Regression Analysis; Risk Factors; Tumor Virus Infections; Uterine Cervical Dysplasia; Vitamin B 12