[Atypical regenerative changes, dysplasia, and carcinoma in situ in chronic gastritis associated with Helicobacter pylori]. / Cambios regenerativos atípicos, displasia y carcinoma in situ en gastritis crónica asociada con Helicobacter pylori.

In the present work we study the association between chronic active gastritis (CAG), atypical regeneration and dysplasia and gastric Helicobacter pylori (HP) infection. We study two groups of endoscopic biopsies. Regenerative changes and dysplasia were evaluated according to Gandur-Maymneh et al. classification which was simplified in typical and atypical regeneration, and mild and severe dysplasia. The group I included 94 patients with CAG, 9 with chronic non active gastritis (CNAG) and 2 with normal gastric mucosa. CAG was graded according to activity in; severe 28 patients; moderate 54 patients and; mild 12 patients. HP association in these cases was 100%, 77% and 25%. In cases of CNAG HP was present in 22%, there were not HP in normal gastric mucosa. There were atypical regeneration in 25% of moderate CAG and in 42% of severe CAG. Mild dysplasia was present in 7.5 and 25% in cases of moderate and severe CAG. Two biopsies showed severe dysplasia. In addition, intestinal metaplasia was found in 15% of CAG, the metaplasia was present in 25% of cases with CAG and atypical regeneration; in 54% of cases with mild dysplasia and; in 100% on cases with severe dysplasia. The group II included 9 cases of gastric cancer of intestinal type, 7 cases of diffuse type, and 4 cases of mixed type. In all these cases there was viewed CAG associated to HP infection in non-neoplastic mucosa. In 75% of cases there were showed atypical regeneration and 60% presented some type of dysplasia. There was transition between atypical regeneration and dysplasia in 6 cases of intestinal gastric cancer and in 3 cases of mixed type. We found relationship between the intensity of CAG and HP colonization, and the association with atypical regeneration and dysplasia.

Serological response to HPV16 in CIN-III and cervical cancer patients. Case-control studies in Spain and Colombia.

This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/ 1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a L1-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%,7.2%,11.7%,12.6% respectively) than in Spain (17.1 %, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR = 2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden.

Correlación entre variables ginecoobstétricas con lesiones morfológicas por virus del papiloma humano, premalignas y malignas del cérvix uterino / Gyneco-obstetric variables and their correlation with morphological lesions on human papilloma virus, premalignant and malignant lesions of the uterine cervix

Las infecciones en el cérvix uterino y neoplasias intraepiteliales son frecuentes en nuestra población femenina. El objtivo del presente trabajo fue identificar la asociación de neoplasias intraepiteliales del cérvix con alteraciones morfológicas ocasionadas por virus del papiloma humano y definir su correlación con algunas variables ginecoobstétricas. Se seleccionaron 147 casos de 215 con diagnóstico de neoplasias intraepiteliales cerviales efectuando mediante citología cervicovaginal durante el año de 1991. También se revisaron las laminillas de las biopsias correspondientes de cada caso. De los 147 casos, 138 presentaron alteraciones citológicas e histopatológicas de infección por el virus del papiloma humano. El 63 por ciento correspondió a condiloma, el 21 por ciento a displasia más condiloma y el 16 por ciento a carcinoma in situ más condiloma. El tipo de condiloma fue: plano en el 98 por ciento, acuminado en el 1 por ciento y atípico en el 1 por ciento. El promedio de edad de las pacientes fue 36 años y más del 70 por ciento fueron menores de 40 años. El inicio de vida sexual activa antes de los 19 años se asoció con un alto índice de displasia (50 por ciento). En las mujeres que tuvieron el primer parto antes de los 19 años se identificó: condiloma (52 por ciento), displasia (66 por ciento) y carcinoma in situ (50 por ciento); mientras que, en las enfermas con dispositivo intrauterino los porcentajes respectivos para estas lesiones fueron 38, 41 y 35. Se concluye que el mejor control del cáncer cervicouterino en nuestro medio es la prevención a través de examen cervicovaginal, prueba sencilla, útil y de bajo costo. Las campañas de detección oportuna de cáncer cervicouterino deben ocupar un lugar prioritario en las instituciones de salud

[Human papilloma virus in the etiology of cervicouterine cancer]. / El virus del papiloma humano en la etiología del cáncer cervicouterino.

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)

Risk factors for cervical intraepithelial neoplasia grade III/carcinoma in situ in Spain and Colombia.

A case-control study of 525 histologically confirmed cases of cervical intraepithelial neoplasia grade III and 512 controls was done in Spain and Colombia to assess the role of various risk factors taking into account the effect of human papillomavirus (HPV). The presence of HPV DNA, assessed by a polymerase chain reaction-based method, was the strongest risk factor identified. In Spain the adjusted odds ratio (OR) and 95% confidence interval (CI) (numbers in parentheses) were 56.9 (24.8-130.6) and, in Colombia, were 15.5 (8.2-29.4). In addition to HPV, the multivariate analysis revealed independent effects of early age at first intercourse (in Spain ORa, 4.3; 95% CI, 2.0-9.3 for ages < 17 versus 20+ years and in Colombia ORa, 9.0; 95% CI, 2.6-30.9 for ages < 14 versus 20+ years), and antibodies to Chlamydia trachomatis (in Spain ORa, 2.3; 95% CI, 1.1-4.5; and in Colombia ORa, 1.7; 95% CI, 1.1-2.7). High parity showed a significant effect only in Colombia (ORa, 2.0; 95% CI, 1.0-5.0 for > or = 6 versus 1) while number of partners of the woman and specially of her husband showed a strong effect in Spain only (ORa, 6.9; 95% CI, 3.1-15.3 for partners of the husband > or = 21 versus 1-5). Smoking and use of oral contraceptives did not show significant or consistent associations. Among HPV-DNA positive women early age at first intercourse and high parity increased the risk of cervical intraepithelial neoplasia III but the effect was statistically significant only for the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Human papillomavirus and cervical intraepithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia.

A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III.

Human papillomavirus type 16 variants isolated from vulvar Bowenoid papulosis.

Tissues from two cases of Bowenoid papulosis of the vulva were found to contain human papillomavirus (HPV) 16 DNA by Southern blot hybridization. Analysis of the hybridization pattern revealed differences in a restriction fragment of one specimen as compared to the HPV 16 DNA prototype. To investigate if these differences could interfere with the expression of such oncogenic viral genomes, the corresponding DNA fragments were cloned and further analyzed. After amplification by PCR and DNA sequencing, a 213 base pairs duplication was mapped in the long control region (LCR) of this HPV 16 variant. One single PCR fragment was obtained from the other Bowenoid papulosis, which is identical in size with the same region in the HPV-16 prototype. The duplication in the HPV-16 LCR analyzed in this study maps upstream of a region containing several regulatory elements.

[Molecular aspects of human papillomaviruses and their relation to uterine cervix cancer]. / Aspectos moleculares de los papilomavirus humanos y su relación con el cáncer cérvico-uterino.

Papillomaviruses (wart viruses) are responsible for the development of benign and malignant epithelial lesions in mammals. More than 60 different types of human papillomaviruses (HPVs) have been isolated to date. Some of them are major candidates as etiologic agents in cervical cancer. DNA from HPV types 16, 18 and 33 is usually found integrated in about 90 percent of genital carcinomas. Integration of the viral DNA into the cellular genome may be an important step towards the development of malignancy. Two early genes of HPVs (E6 y E7) are involved in cellular transformation. Another early gene (E2) participates in gene control by directly binding to conserved DNA motifs in the viral genome. Several protein factors of viral and cellular origin interact with the regulatory region of HPVs and participate in the regulation transcription of oncogenes E6 and E7. Cellular factors, such as immune system and oncogene and anti-oncogene alterations, seem to play an important role in papillomavirus-associated cervical carcinogenesis.

[Carcinoma in situ and human papillomavirus infection]. / Carcinoma in situ e infección por virus papiloma humano.

The paperwork objective is to analyze if the HPV infections are associated to Ca in situ (CIS). The cytologic, colposcopic and histologic examinations of women affected by CIS were revised. It was determined that a group of them were also infected by HPV. On them, it was determined the viral genotype by nucleic acids hybridization. The Toki score was also utilized.

Carcinoma in situ e infección por virus papiloma humano / Carcinoma in situ and human papillomavirus infection

El objetivo del presente trabajo es analizar si la infección por virus papiloma humano (HPV) se asocia al carcinoma in situ (CIS). Con esta finalidad se revisó la citología, colposcopia e histología de mujeres con CIS. En un grupo de ellas se determinó la infección por HPV y se estableció cual era el genotipo viral mediante la técnica de hibridización de ácidos nucléicos. Se utilizó, también, la puntuación de Toki