N Muñoz

Johns Hopkins Hospital

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F. Xavier Bosch

Vall d'Hebron Hospital Universitari

K. V. Shah

University of Lincoln

Xavier Castellsagué

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública

Sílvia de Sanjosé

Hospital Universitari Germans Trias i Pujol

M Gili

Hospital Universitario Virgen Macarena

Nieves Ascunce

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública

E Guerrero

University of the Andes

Vanda Hofmannová

Institute of Haematology and Blood Transfusion

Julian Peto

London School of Hygiene & Tropical Medicine

L Tafur

National University of Cajamarca

Cooperative Institutions

Centre International de Recherche sur le Cancer

Institut Català d'Oncologia

Johns Hopkins University

National Institutes of Health

National Cancer Institute

London School of Hygiene & Tropical Medicine

University of Oxford

Division of Cancer Epidemiology and Genetics

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública

Institut d'Investigació Biomédica de Bellvitge

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[Esophageal cancer: its epidemiology, risk factors and prevention].

PubMed (1997)

Xavier Castellsagué N Muñoz

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Citations (1)

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

PubMed (1993)

N Muñoz F. Xavier Bosch Sílvia de Sanjosé P Viladiu José R. Tormo

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

Etiology

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Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

Journal of Clinical Oncology (1997)

P. Viladiu F. Xavier Bosch Xavier Castellsagué N Muñoz Josep M. Escribà

PURPOSE To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

10.1200/jco.1997.15.2.610

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Citations (44)

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

Journal of Clinical Microbiology (1994)

Yeping Sun K. V. Shah Martin Müller N Muñoz Xavier Bosch

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.

10.1128/jcm.32.9.2216-2220.1994

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Social differences in sexual behaviour and cervical cancer.

PubMed (1997)

Sílvia de Sanjosé F. Xavier Bosch N Muñoz K. V. Shah

In this chapter we first describe the variation of cervical cancer in relation to social class. Thereafter we examine the causes for the occurrence of socioeconomic differences in invasive cervical cancer, using data from two case-control studies carried out in Colombia and Spain. Cervical cancer is the most common cancer in developing countries and the sixth most common in developed countries. In all areas, it is more frequent among women of low socioeconomic status, it is associated with multiple sexual partners and early age at first sexual intercourse, and both incidence and mortality are reduced by screening. According to population-based surveys in industrialized countries, men of low socioeconomic status report fewer sexual partners than men of high socioeconomic status but there is no clear indication that the same is true of women of low socioeconomic status. In the case-control studies in Spain and Colombia, the human papillomavirus and all other sexually transmitted diseases were more prevalent among women in low socioeconomic strata. Number of sexual partners and particularly contacts with prostitutes were higher among husbands of women of low socioeconomic status. Other potential risk factors for the disease, such as smoking and oral contraceptive use, and also cervical cancer screening (Pap smears), were more common in women of high social strata. Women with no schooling had a threefold higher risk in Spain and a fivefold higher risk in Colombia of having cervical cancer compared with women who had achieved a higher educational level. After adjustment for sexual behaviour, HPV DNA status, history of Pap smears and husband's contact with prostitutes, this association was considerably reduced. These results are indicative that socioeconomic differences in the incidence of cervical cancer can be partly explained by differences in the prevalence of HPV DNA. Men's sexual behaviour and particularly contacts with prostitutes might be a major contributor to the higher prevalence of HPV DNA among the poor.

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Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective

Journal of Virology (1997)

Takashi Yamada M. Michele Manos Julian Peto Catherine E. Greer N Muñoz

We examined intratype human papillomavirus type 16 (HPV-16) sequence variation in tumor samples that were collected and analyzed in an international study of invasive cervical cancer. The collection included tumors from 22 countries in five continents. Using our recently developed E6 and L1 PCR-based hybridization systems to distinguish HPV-16 variant lineages, we analyzed material from tumors previously found to contain HPV-16 DNA. Of 408 specimens analyzed in the E6 hybridization assay, 376 (92.2%) belonged to previously reported HPV-16 variant lineages. The remaining 32 specimens (7.8%) harbored HPV-16 variants with novel hybridization patterns, novel nucleotide changes, or both. Nucleotide sequences (1,203 bp) were determined for the E6, the MY09/11 region of L1, and the long control region of each novel variant and representative specimens from each hybridization pattern observed. Based on E6 hybridization patterns, most of the variants from European and North American samples were phylogenetically classified as European prototype (E) while samples from Africa contained primarily African 1 (Af1) or African 2 (Af2) variants. The majority of Asian (As) variants were observed in Southeast Asia, and almost all Asian American (AA) variants were from Central and South America or Spain. A single North American 1 (NA1) variant was detected in a tumor from Argentina. Nucleotide changes previously shown to covary between the MY09/11 region of L1 and the E6 coding region were examined in a subset of 249 specimens. We observed 22 combined E6-L1 hybridization patterns, of which 11 (in 21 samples) were novel. No unanticipated nucleotide covariation was observed between the E class and the AA-Af1-Af2-NA1 classes, suggesting the absence or rarity of genomic recombination between HPV-16 lineages. This extensive description of HPV-16 variants forms a basis for further examining the relationship between intratype variation and basic functional differences in biological activities. HPV-16 variants may prove important for the determination of the risk of cervical neoplasia and for the design of HPV-16 vaccine strategies.

Coding region

10.1128/jvi.71.3.2463-2472.1997

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Citations (428)

The epidemiology of human papillomavirus and cervical cancer.

N Muñoz F. Xavier Bosch K. V. Shah A. Meheus

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Citations (161)

Cervical Carcinoma and Sexual Behavior: Collaborative Reanalysis of Individual Data on 15,461 Women with Cervical Carcinoma and 29,164 Women without Cervical Carcinoma from 21 Epidemiological Studies

Cancer Epidemiology Biomarkers & Prevention (2009)

T Tajkumar Jack Cuzick Rowan Appleby Beral Amy Berrington de González

Abstract High-risk human papillomavirus (HPV) types cause most cervical carcinomas and are sexually transmitted. Sexual behavior therefore affects HPV exposure and its cancer sequelae. The International Collaboration of Epidemiological Studies of Cervical Cancer has combined data on lifetime number of sexual partners and age at first sexual intercourse from 21 studies, or groups of studies, including 10,773 women with invasive cervical carcinoma, 4,688 women with cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, and 29,164 women without cervical carcinoma. Relative risks for invasive cancer and CIN3 were estimated by conditional logistic regression. Risk of invasive cervical carcinoma increased with lifetime number of sexual partners (P for linear trend <0.001). The relative risk for ≥6 versus 1 partner, conditioned on age, study, and age at first intercourse, was 2.27 [95% confidence interval (95% CI), 1.98-2.61] and increased to 2.78 (95% CI, 2.22-3.47) after additional conditioning on reproductive factors. The risk of invasive cervical carcinoma increased with earlier age at first intercourse (P for linear trend <0.001). The relative risk for age at first intercourse ≤14 versus ≥25 years, conditioned on age, study, and lifetime number of sexual partners was 3.52 (95% CI, 3.04-4.08), which decreased to 2.05 (95% CI, 1.54-2.73) after additional conditioning on reproductive factors. CIN3/carcinoma in situ showed a similar association with lifetime number of sexual partners; however, the association with age at first intercourse was weaker than for invasive carcinoma. Results should be interpreted with caution given the strong correlation between sexual and reproductive factors and the limited information on HPV status. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1060–9)

Sexual intercourse

Carcinoma in situ

10.1158/1055-9965.epi-08-1186

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In vivo nitrosoproline formation and other risk factors in Costa Rican children from high- and low-risk areas for gastric cancer.

PubMed (1993)

Rosa A. Sierra Anne Chinnock Hiroshi Ohshima Brigitte Pignatelli C. Malaveille

The hypothesis that intragastric synthesis of N-nitroso compounds (NOC) in early life could play a role in gastric carcinogenesis was tested by applying the N-nitrosoproline (NPRO) test to about 50 children living in high- and low-risk areas for stomach cancer in Costa Rica. The median values of excretion of NPRO and the sum of three nitrosamino acids (micrograms/12 h urine) were 10-20% of those in adults from other geographical high-risk areas for stomach cancer. The urinary NPRO level after proline intake was higher in children from the high-risk area (P < 0.04) and markedly reduced after ingestion of ascorbic acid together with proline (P < 0.05). NPRO levels on the day of proline intake were highly correlated with levels of nitrate excretion (P < 0.001). Mean levels of total NOC in an aqueous (pH 2) extract of cooked beans from the high- and low-risk areas were similar. Acid-catalyzed nitrosation of the extract increased the total NOC concentration up to 1000-fold, but there was no difference between samples from the two areas. About 10% of bean extracts from both areas showed weak direct-acting genotoxicity in Escherichia coli; after acid-catalyzed nitrosation, all samples were genotoxic at similar levels. The diet of children in the low-risk area satisfied recommended levels of intake of energy and most nutrients except riboflavin and retinol equivalents. Diets from the high-risk area were deficient in energy intake and all nutrients except protein and vitamin C.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrosation

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The epidemiology of cervical cancer and humen papillomavirus

International Agency for Research on Cancer eBooks (1992)

N Muñoz

Use of sensitive molecular biological methods for detecting human papillomavirus (HPV) in epidemiological studies has produced convincing evidence that this virus plays a causal role in cervical cancer. This volume reviews the traditional and molecular epidemiological evidence, and the natural history of HPV infection. The various methods for type-specific detection of HPV are examined, as well as methods for identifying the presence of other sexually transmitted agents that have been postulated at various times as having a role. Applications of knowledge of the importance of HPV in cervical cancer aetiology discussed include use of detection of the virus in screening for women at risk of the cancer and also in determining suitable clinical treatment of women with suspected precancerous lesions.

Etiology

Molecular Epidemiology

Papillomaviridae

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