PubMed Health⌕ Search

Biomedical subjects

N Muñoz

Publications and source records attributed to N Muñoz.

At least 109 records · Page 6Linked to original sources

The role of HPV in the etiology of cervical cancer.

To assess the association between human papillomavirus (HPV) and cervical cancer we have carried out two case-control studies of cervical intraepithelial neoplasia grade III (CIN III) (525 cases and 512 matched controls) and two case-control studies of invasive squamous cell carcinoma (436 cases and 387 population controls) in Cali, Colombia and nine provinces of Spain. HPV DNA detected by polymerase chain reaction, a PCR-based hybridization assay in the exfoliated cells of the uterine cervix, was the strongest risk factor in both countries. For invasive cancer the adjusted odds ratios and 95% confidence intervals were: 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Columbia and for CIN III they were: 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Columbia. This strong association was specific for types 16, 18, 31, 33 and 35 and also for HPV types not yet characterized. Hormonal factors such as oral contraceptives and high parity appear to confer an additional risk increasing the progression from chronic HPV infection to cancer. Our overall results indicate that HPV is the main cause of cervical cancer in two countries with contrasting rates of cervical cancer, Columbia having an incidence rate about 8 times higher than Spain.

Adolescent↗

Sexually transmitted agents and cervical neoplasia in Colombia and Spain.

Case-control studies of cervical intra-epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN-III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive-cancer studies included 373 histologically confirmed cases of squamous-cell carcinoma and 387 age-stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex virus type II (HSV-2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase-chain-reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV-2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sero-prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV-2 and those with antibodies to C. trachomatis. These associations were present only in HPV-DNA-negative women. Among HPV-DNA-positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV-2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiological significance.

Case-Control Studies↗

Difficulty in eradicating Helicobacter pylori in a population at high risk for stomach cancer in Venezuela.

The bacterium Helicobacter pylori (HP) has been implicated in the etiology of precancerous lesions of the stomach and there is evidence suggesting that it may influence the efficacy of chemoprevention of gastric cancer with vitamin C. Eradication seldom has been attempted in populations from developing countries, with a high prevalence of HP frequently resistant to metronidazole. A randomized, double-blind, controlled trial to evaluate the efficacy of colloidal bismuth subcitrate (120 mg q.i.d.) and amoxycillin (500 mg q.i.d.) in eradicating HP was conducted in 220 subjects drawn from a population with a high prevalence of metronidazole-resistant HP in Tachira state, Venezuela. One month after completion of two weeks' treatment, eradication rates of 6.5 percent in the treatment group and two percent in the placebo group were estimated on the basis of HP diagnosis in biopsies, and of 13.9 percent compared with 3.9 percent on the basis of a 14C-urea breath test, although the negative predictive value of the breath test was very low compared with HP diagnosis in biopsies. In the treatment group, particularly among males, a significant decrease in bacterial load was detected. Reasons for failure of treatment in high HP-prevalence areas are discussed, and it is suggested that primary prevention of HP infection may be the optimal approach to reducing levels of stomach cancer in these high-risk groups.

Adult↗

Human papillomavirus and invasive cervical cancer in Brazil.

A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer.

Adult↗

Comparison of peptide enzyme-linked immunosorbent assay and radioimmunoprecipitation assay with in vitro-translated proteins for detection of serum antibodies to human papillomavirus type 16 E6 and E7 proteins.

Antibodies to human papilloma virus (HPV) type 16 (HPV-16) E6 and E7 proteins in serum are markers for HPV-associated invasive cervical carcinoma. We compared two assays, a radioimmunoprecipitation assay with in vitro-translated HPV-16 E6 and E7 proteins and an enzyme-linked immunosorbent assay (ELISA) with E6 and E7 synthetic peptides, for their abilities to discriminate serologically between patients with invasive cervical cancer and controls. Among the patients, antibody prevalences were higher by the E6 radioimmunoprecipitation assay (55.7%) than by the E6 peptide ELISA (15.5%), but among the controls, they were lower by the radioimmunoprecipitation assay (1.7%) than by the E6 peptide ELISA (5%). For E7, antibody prevalences among the patients were comparable by the radioimmunoprecipitation assay (43%) and the peptide ELISA (41%), but among the controls they were higher by the E7 peptide ELISA (17.4%) than by the radioimmunoprecipitation assay (4.1%). There was good agreement between the E7 radioimmunoprecipitation assay and the E7 peptide ELISA among patients but not among controls. In tests with representative sera, heat denaturation of the translated proteins resulted in a complete loss of reactivity to the E6 protein and a marked decrease in reactivity to the E7 protein. Our study showed that the radioimmunoprecipitation assay discriminates better than the peptide ELISA between patients with invasive cervical cancer and controls and that this is related to the ability of the radioimmunoprecipitation assay to detect conformational epitopes.

Antibodies, Viral↗

Cervical cancer.

The overall incidence of and mortality from cervical cancer has declined in western countries and in most developing countries. In women under 40 years of age, however, mortality rates are levelling off or increasing in most countries. The earliest and most marked increases in young women occurred in England and Wales, Scotland, Ireland, New Zealand and Australia. Mortality rates in young women from eastern European countries began to increase later than in the UK, but the increases are of concern because baseline mortality rates are high in these countries. The reasons for the overall decline in cervical cancer are largely unknown but appear to be linked to improvements in the general standard of living. The increases in young women may well be due to the increasing prevalence of HPV infection. Screening for cervical cancer has undoubtedly led to a decline in cervical cancer incidence and mortality in many countries, but its contribution to the trends is difficult to assess without further information.

Adult↗

Human papillomavirus-related serological markers of invasive cervical carcinoma in Brazil.

Masked sera from 194 cases and 217 controls participating in a case-control study of cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 E6 and E7 by radioimmunoprecipitation assay. Radiolabeled full-length E6 and E7 proteins expressed by in vitro transcription and translation in rabbit reticulocyte lysate were used as antigens. The antibody prevalences in cases and controls were: 54.1% versus 6% for E6; 30.4% versus 4.6% for E7; 63.4% versus 10.1% for either E6 or E7; and 21.1% versus 0.5% for both E6 and E7. The corresponding odds ratios were 35 ([95% confidence interval (CI)], 15-83), 10 (95% CI, 4-25), 28 (95% CI, 13-61) and 87 (95% CI, 10-736). The most marked contrast between cases and controls was observed for sera with high antibody titers (cpm > 6000) with an odds ratio of 239 (95% CI, 29-1946) for E6 or E7. Seroreactivity in cases was partially type specific; women who had HPV-16 DNA in the genital tract had higher antibody prevalence rates than those who were negative for HPV DNA. Reactivity to the E6 protein was associated with the stage of disease; the antibody prevalence was 62.7% in cases with stages II-IV and 31.0% in cases with stage I (P < 0.005). HPV-16 serology and HPV polymerase chain reaction were compared as markers for invasive cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serologic response in human papillomavirus-associated invasive cervical cancer.

Human papillomavirus (HPV) transforming proteins E6 and E7 are uniformly expressed in HPV-associated cervical cancer. Our objective was to measure antibodies to HPV-16 E6 and E7 proteins in cervical cancer patients using an assay which would detect antibodies to conformational epitopes. Serum specimens obtained from two case-control studies of HPVs and cervical cancer were tested. The studies were performed in Cali, Colombia, South America and in 9 provinces of Spain. Cases consisted of women with invasive cervical cancer associated with HPV-16 or other HPV types and women with HPV-16-associated high-grade cervical intra-epithelial neoplasia (CIN-3). Controls for invasive cases and CIN-3 cases were women who had no cytologic abnormalities and who were matched for age and country of residence. Serum antibodies to HPV-16 E6 and E7 proteins were detected by radio-immunoprecipitation of in vitro translated proteins. Antibodies to the E6 and E7 protein were observed among 56% and 43%, respectively, of invasive cases and 1.7% and 4.1%, respectively, of controls. Antibodies to either protein were detected in 72% of sera from invasive cases and 5.8% of sera from controls. High antibody reactivity and antibodies to both proteins were found almost exclusively in invasive cases. The frequency of antibodies to the E6 protein and the E7 protein among CIN-3 cases did not differ significantly from the CIN-3 controls. Five women with HPV-18-associated invasive cervical cancer were negative for serum antibody to HPV-16 E6 and E7 proteins. Antibodies to HPV-16 E6 and E7 proteins appear to be partially virus-specific and disease state-specific markers of HPV-associated cervical cancer.

Antibodies, Viral↗

Mutagens, N-nitroso compounds and their precursors in gastric juice from patients with and without precancerous lesions of the stomach.

This study examined whether elevated risk of gastric cancer is associated with high levels of total N-nitroso compounds (NOC), their precursors and nitrosation-dependent genotoxins in gastric juice (GJ). An improved method for quantifying total NOC was used and genotoxicity was assayed in E. coli. Results from patients (n = 210) with or without precancerous lesions of the stomach and living in three areas with up to 8-fold variations in gastric cancer risk (U.K., France, Colombia) were compared. The level of nitrite (range < 1-472 mumol/l) was found to increase with the pH of GJ from the three countries and was dependent on country of collection. The levels of NOC (range: < or = 0.01-8.0 mumol/l) in GJ were not affected by stomach histology and country of collection. NOC levels increased linearly with nitrite concentrations, but the slope of the regression line was greater for acidic GJ (pH < or = 4). These data together suggest that chemical nitrosation contributes at least as much as other nitrosation pathways to the intragastric formation of NOC. Acid-catalysed nitrosation of GJ in vitro increased the NOC concentration (range: 7-1332 mumol/l) up to several 1000-fold but this increase was not predictive of gastric cancer risk either by country or by stomach histology. After acid-catalysed nitrosation, direct genotoxicity (SOS-inducing potency) was significantly higher in GJ with original pH > 4 and highest in samples from Colombia. The results (a) provide no support that intragastric total NOC levels are elevated in subjects with precancerous stomach lesions or living in a high risk area for stomach cancer; (b) confirm that a high nitrite level and elevated pH in GJ are strongly associated, the level of nitrite being associated with precancerous stomach conditions only in Colombia; (c) reveal the presence of precursor compounds in GJ, that after nitrosation yield direct mutagens that probably contain NOC and other substances. As their concentrations were significantly higher in achlorhydric subjects and highest in Colombian patients, these data together provide support for a role of intragastrically formed nitrite-derived direct mutagens in gastric cancer aetiology.

Adult↗

Prevalence survey of precancerous lesions of the oesophagus in a high-risk population for oesophageal cancer in France.

The prevalence of precancerous lesions of the oesophagus and their association with alcohol drinking, tobacco smoking and some dietary factors were examined in an endoscopic survey carried out in Lower Normandy, France, a high-risk area for oesophageal cancer. The study included 134 male volunteers of 35-64 years of age. In 124 of the volunteers oesophageal biopsies were evaluable. At histology, the prevalence of chronic oesophagitis, epithelial atrophy and dysplasia was 63%, 1.6% and 4.8%, respectively. The prevalence of these precancerous lesions was significantly associated with cigarette smoking and frequent consumption of butter.

Adult↗

p53 gene mutations and MDM2 amplification are uncommon in primary carcinomas of the uterine cervix.

The p53 gene is the most frequently altered gene known thus far in a wide variety of human cancers. Inactivation of p53, either through mutation or through interaction with the human papillomavirus (HPV) E6 oncoprotein, is a characteristic feature of all cervical carcinoma cell lines that have been studied. These findings suggest that p53 inactivation is required for cervical carcinoma development and that HPV infection and p53 mutation may be mutually exclusive. We have studied the p53 gene in 35 primary cervical carcinomas. DNA sequence and single strand conformational polymorphism analyses were used to evaluate p53 in 27 squamous carcinomas (25 HPV-positive) and eight adenocarcinomas (four HPV-positive). A missense mutation of p53 was observed in one HPV 16-positive squamous carcinoma, demonstrating that p53 mutations can occur in combination with HPV infection. The HPV-negative tumors all lacked p53 gene mutations. The absence of p53 mutations in HPV-negative cases prompted an assessment of tumors for MDM2 gene amplification. The MDM2 gene encodes a p53 binding protein and has been found to be amplified in some human tumors lacking p53 mutations. MDM2 amplification was not identified in any of the tumors we examined, including four HPV-negative cases. Our findings show that HPV infection and p53 gene mutation are not mutually exclusive and suggest that many HPV-negative carcinomas may arise via a pathway independent of p53 inactivation.

Adenocarcinoma↗

[Human papilloma virus in the etiology of cervicouterine cancer].

The objectives of this study were to confirm the hypothesis that invasive carcinoma of the uterine cervix and the precursors of that condition are most often caused by human papilloma virus (HPV) infections, and to determine whether or not other risk factors are involved in the neoplastic process. For this purpose, four concurrent case-control studies were carried out. Two included cases of invasive cervical cancer and population-based controls. The other two included cases of in situ carcinoma and controls. Research was carried out in nine provinces of Spain and in Cali, Colombia. The identification of cases took place between June 1985 and June 1988. The studies included 436 incident cases of invasive carcinoma and 387 controls, selected at random from the corresponding populations, and 525 cases of in situ carcinoma and 512 controls paired by age, place of recruitment, and date that cytological specimens were taken from the women participating in cytological screening programs. Exposure to HPV was detected through hybridization tests after amplification by polymerase chain reaction (PCR) in exfoliated cervical cells from cases and controls. Exposure to HPV was the principal risk factor in the four studies. For invasive carcinoma, the relative risk and 95% confidence interval were 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Colombia. For in situ carcinoma, the figures were 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Colombia. This strong association was specific for types 16, 18, 31, 33, and 35 as well as still-unclassified HPV types.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma in Situ↗

[Attitude and behavior regarding breast self examination among health professionals in Chile].

This study was carried out from April to December 1990 in the commune of Valdivia, Chile and involved 207 physicians, nurses, midwives, and nurse-midwives. The objective was to determine the relationship between subjective attitude and personal behavior on the part of these health professionals with regard to the practice of monthly breast self-examination (BSE). The data were collected by means of an instrument designed to measure attitudes, which was prepared by Victoria Lee Champion (1984) on the basis of the health beliefs model of Becker, et al. (1974). Also included were questions aimed at ascertaining the personal and sociodemographic background of the professionals surveyed and their knowledge of several aspects of breast cancer and BSE. The information collected was subjected to the following tests of validity and reliability: Person product-moment correlation coefficient r, split half method, Spearman-Brown R coefficient, Cronbach alpha coefficient, and the Chi-square test to determine the degree of association between the variables. The results showed that although 79% of the women studied had ample knowledge of many aspects of breast cancer and 82% were aware of the benefits of BSE, only 28% practiced it on a monthly basis. It is alarming that health professionals, who are responsible for teaching prevention measures to other people, have yet to assume responsibility for protecting their own health insofar as early detection of breast cancer is concerned.

Adult↗

The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain.

To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Columbia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0-66.7); SH OR = 6.8 (3.4-13.4); and PCR OR = 28.8 (15.7-52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal.

Carcinoma, Squamous Cell↗