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Biomedical subjects

A M Beckmann

Publications and source records attributed to A M Beckmann.

At least 37 records · Page 2Linked to original sources
PubMed1992

A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.

BACKGROUND: Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. METHODS: We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. RESULTS: Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA: The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae. CONCLUSIONS: Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18.

Adolescent↗
PubMed1992

Human papillomaviruses, herpes simplex viruses, and the risk of oral cancer in men.

A population-based case-control study was conducted in western Washington state to examine the relations between infection with human papilloma viruses (HPV), herpes simplex viruses (HSV), and risk of oral squamous cell cancer in men. Interviews were completed on 131 oral cancer cases diagnosed between January 1985 and December 1989 and 136 controls frequency matched to cases on age and date of diagnosis who were obtained by random digit dialing. The risk for oral cancer among men with 30 or more sexual partners was 2.4 times that of men with four or fewer partners (95% confidence interval (CI) 1.0-5.9). Men who ever practiced oral sex had lower risk for oral cancer relative to men who never practiced oral sex (relative risk (RR) = 0.4, 95% CI 0.2-0.8). Analyses of exfoliated oral cavity cells for the presence of HPV-6 DNA with polymerase chain reaction revealed that men with an oral HPV-6 infection had 2.9 times the risk for oral cancer of noninfected men (95% CI 1.1-7.3), whereas men with an oral HPV-16 infection had 6.2 times the risk for oral cancer of noninfected men (crude RR = 6.2, 95% CI 0.7-52.2). Relative risks associated with serologically detected HSV-1 and HSV-2 infections were 0.8 (95% CI 0.3-1.7) and 1.8 (95% CI 0.7-4.6), respectively. The authors conclude that HPV-6 is associated with oral cancer. Although men infected with HPV-16 and HSV-2 were at elevated risk, these associations may have been due to chance. The role of specific sexual practices in the transmission of viruses to the oral cavity remains unclear.

Antibodies, Viral↗
PubMed1992

Cigarette smoking and the risk of anogenital cancer.

The association between cigarette smoking and cervical cancer has been demonstrated in numerous prior studies. As part of population-based case-control studies of cancers of the vulva, vagina, cervix, anus, and penis in relation to infection with human papillomavirus, conducted in western Washington State and the province of British Columbia from the mid 1980s until the present time, the authors have collected detailed information on smoking history. The proportion of subjects who were current smokers of cigarettes ranged from slightly over 40% among incident cases of vaginal and cervical cancer to 60% among cases of vulvar and anal cancer. In contrast, only about 25% of controls were current smokers. The adjusted odds ratios (OR) associated with current smoking were substantially elevated (OR = 1.9-14.6) for all cancer sites except cancer of the vagina (OR = 1.3). The risks tended to increase in proportion to the number of cigarettes smoked. For most cancer sites, the odds ratios associated with former smoking were substantially less than those associated with current smoking and diminished with increasing time since cessation of smoking. The authors' data and those of other investigators suggest that cigarette smoking plays a role in the etiology of anogenital cancers and that smoking has a late-stage or promotional effect.

Adolescent↗
PubMed1991

Human papillomavirus infection in women with multicentric squamous cell neoplasia.

Tissues from 32 women with multicentric squamous cell neoplasia of the anogenital region (72 anatomically distinct lesions at the cervix, vagina, vulva, perineum, or anus) were tested for the presence of human papillomavirus with the polymerase chain reaction or in situ hybridization. All the women had invasive carcinomas or grade 3 intraepithelial neoplasia lesions at a minimum of one site and one or two squamous cell lesions at another site(s). Human papillomavirus was detected in all of the multicentric lesions in 87.5% (28/32) of the women and in at least one lesion in 12.5% (4/32). In the 28 women with detectable human papillomavirus at all sites, 61% (17/28) had the same virus type(s) at all sites (types 6, 16, 6 and 16, 33) and 25% (7/28) had 6 or 16 at one site and both viruses at the other site(s). Four women (15%) had different virus patterns in the separate lesions.

Adult↗
PubMed1991

Genital-type human papillomavirus infection is not associated with surface epithelial ovarian carcinoma.

Tumor tissues from 29 women with borderline or malignant epithelial ovarian tumors were examined for the presence of human papillomavirus (HPV) DNA by the polymerase chain reaction (PCR). The PCR analysis used a set of consensus primers that are complementary to highly conserved sequences in the genital HPVs (M. M. Manos, Y. Ting, D. K. Wright, A. J. Lewis, T. R. Broker, and S. M. Wolinsky, Cancer Cells 7, 209-214, 1989). Amplification products were detected by Southern hybridization with consensus oligonucleotide probes. A total of 70 paraffin-embedded tissue sections from ovarian carcinomas were tested and we did not detect genital-type HPV DNA sequences in any of these specimens. However, all of the tissue specimens were considered adequate for PCR analysis because a human cellular gene (beta-globin) was successfully amplified in each tissue specimen. In addition, HPV 16 DNA was found in a concurrent invasive squamous-cell carcinoma of the cervix from one ovarian cancer patient, indicating that the PCR was able to detect HPV in the lower genital tract of this individual. We conclude that there is no association between infection with the most common genital HPVs and borderline and malignant epithelial ovarian tumors.

Adult↗
PubMed1991

Comparative virologic studies of condylomata acuminata reveal a lack of dual infections with human papillomaviruses.

Condylomata acuminata are epithelial proliferations caused by infection of the anogenital squamous epithelium with human papillomavirus (HPV). DNA-DNA hybridization techniques and the extremely sensitive polymerase chain reaction (PCR) were used to analyze biopsies from patients with clinically diagnosed condyloma acuminatum for the presence of HPV DNA. PCR analyses using primers and oligonucleotide probes specific for the E6/E7 region of HPV-6, -11, or -16 showed that 31 (93.9%) of 33 tissue biopsies contained HPV DNA: 22 contained type 6 DNA, 6 contained type 11 DNA, and 3 contained type 16 DNA. Eleven biopsies positive by PCR were Southern hybridization-negative or were considered inadequate for Southern analysis. In all 11, the presence of HPV DNA was corroborated by the observation of histopathologic evidence suggestive of HPV infection or by in situ hybridization. No evidence of multiple infections with HPV-6 or -11 and HPV-16 was seen.

Adult↗
PubMed1990

Evidence of prevalent genital-type human papillomavirus infections in adults and children.

Recombinant proteins encoded by the E2, E7, L1, and L2 open reading frames (ORF) of human papillomavirus (HPV) types 6b, 16, and 18 were used in Western blot assays to detect serum IgG antibodies in women attending a sexually transmitted diseases clinic (n = 92) and in hospitalized children (n = 81). Antibodies to late gene products (L1 or L2 ORF) were more common than antibodies to early gene products (E2 or E7), both in the adults and the children; overall, the antibody prevalences in the children and the sexually active adults were not significantly different. Human sera with high titers of antibodies to the HPV16 E7 recombinant protein immunoprecipitated the genuine HPV16 E7 protein from the cervical carcinoma cell line CaSki. As an independent measure of HPV infection, the polymerase chain reaction was used to detect HPV6b and HPV16 in oral mucosal scrapings from adults (n = 35) and preschool children (n = 21). In adults, HPV6b and HPV16 DNA were detected in 17% and 23% of oral mucosal samples, respectively. In preschool children, HPV6b and HPV16 DNA were found in 24% and 19% of oral samples, respectively.

Adolescent↗
PubMed1989

Human papillomavirus infection and anal cancer.

To study the association of human papillomavirus (HPV) infection with anal cancer, we examined tissue specimens from 126 patients with malignant lesions of the anal skin or mucosa. The patients were enrolled in a population-based, case-control study of ano-rectal cancer which is being conducted in the state of Washington and the Province of British Columbia. Histologic sections from formalin-fixed, paraffin-embedded tissues were tested for the presence of HPV DNA by in situ hybridization with biotin-labelled HPV 6, 11, 16, 18 and 31 DNA probes. HPV DNA sequences were found in tumor tissues from 24 of the 126 subjects (19.0%). When only squamous neoplasms are considered, 23 of 70 subjects (32.9%) had lesions which contained detectable HPV DNA. One HPV-positive patient had a cloacogenic carcinoma that contained regions of squamous differentiation and it was in these squamous cells that HPV DNA was localized. Of the 23 squamous lesions that harbored detectable HPV DNA, 8 contained HPV 6, 10 contained HPV 16, 1 contained HPV 18 and 4 contained an unclassified virus type(s). HPV DNA was found in tissues from 14 patients with carcinoma-in situ and 10 subjects with invasive carcinoma. These results demonstrate that some malignant tumors of the anus, in both men and women, are associated with HPV infection. We conclude that the anal squamous epithelium is another site where infection with the common genital tract HPVs may carry a risk of malignant transformation.

Adenocarcinoma↗
PubMed1989

Prevalence of genital papillomavirus infection among women attending a college student health clinic or a sexually transmitted disease clinic.

We examined 454 women randomly selected from a Sexually Transmitted Disease (STD) Clinic and 545 consecutive college women undergoing annual examination. Patients were examined for visible genital warts, koilocytes, and human papillomavirus (HPV) antigen on cervical smears and for cervical HPV DNA types 6, 11, 16, 18, and 31. Genital warts were found in 11% of STD Clinic patients and 2% of students (P less than .001). Among those women without genital warts, HPV DNA or antigen was detected in cervical specimens from 10.6% of STD Clinic patients and 11.4% of students (P = .73), with HPV type 16, 18, or 31 being 9.8 times more frequent than cervical HPV 6 or 11 among students and 5.8 times more frequent among STD Clinic patients. Dysplasia was present in 53% of those with HPV type 6 or 11 and in 41% of those with HPV type 16, 18, or 31 DNA.

Adult↗
PubMed1988

Detection of human papillomavirus capsid antigens in various squamous epithelial lesions using antibodies directed against the L1 and L2 open reading frames.

HPV6 and HPV16 infect the squamous epithelium of the genital tract and are thought to be involved in the pathogenesis of benign and malignant lesions. HPV6 is primarily found in benign condylomas whereas HPV16 is present in dysplasias and in invasive squamous cell carcinomas. To examine the expression of the major and minor capsid proteins in these lesions polyclonal antisera directed against bacterially derived fusion proteins harboring different restriction fragments of the L1 and L2 ORFs of HPV6b and HPV16 were generated. L1 ORF-specific antisera were not type-specific and detected the major capsid antigen in lesions infected with related HPV types. Anti-L2 ORF antisera could distinguish among HPV1, HPV6, and HPV16 when the fusion protein used as the immunogen did not harbor the amino-terminus of the L2 ORF. The anti-L1 ORF antisera were employed to detect the major capsid protein in various lesions by immunohistochemical staining. Lesions harboring HPV16 were positive in a high percentage of cervical intraepithelial neoplasia I-II (87%), and less frequently in carcinomas in situ (29%) or invasive carcinomas (17%). In all cases capsid antigen expression was restricted to cells showing some differentiation at the surface or periphery of the lesion.

Antigens, Viral↗
PubMed1988

Human papillomavirus type 16 in multifocal neoplasia of the female genital tract.

We examined lesions from six women with multifocal neoplasia of the lower genital tract (vulva and cervix or vulva and vagina) for the presence of human papillomavirus (HPV) DNA sequences by DNA-DNA in situ hybridization. Cervical tissue specimens from four of the five women with carcinoma in situ (CIS) of the cervix were found to contain HPV type 16 DNA sequences. Vulvar lesions from three of these women also contained HPV-16 DNA and were histologically consistent with CIS. In each instance, hybridization with HPV-16 DNA probes was seen only in areas of the epithelium that contained evidence of surface maturation or koilocytotic atypia (KA). The HPV DNA was not visualized in regions of these lesions in which the full thickness of the epithelium was occupied by poorly differentiated cells. Virus capsid antigens were only detected in a very few cells in two of the four cervical lesions that contained HPV-16 DNA. HPV type 16, which has consistently been associated with the development of cervical cancer, is further implicated as an agent in the pathogenesis of genital cancers by demonstration of the virus genome in neoplasia at nonadjacent sites.

Adult↗
PubMed1986

Methods for diagnosing papillomavirus infection.

The morphology of the lesion and the site in which the lesion is found are the initial clues in classifying papillomavirus-induced neoplasia. Human papillomavirus (HPV) types have limited site-specificity and differ in their association with benign or malignant neoplastic development. Cytopathology, electron microscopy, antigen detection and molecular hybridization all play a role in the armamentarium of diagnostic methods. Although nitrocellulose blotting procedures provide the most accurate and sensitive method for detecting and characterizing viral nucleic acid sequences, recent improvements in cytological hybridization methods allow for rapid detection of virus and analysis of HPV type directly in biopsied tissue and in cervical smears. In particular, these in situ hybridization procedures facilitate retrospective studies of stored specimens.

Adult↗
PubMed1986

Detection of viral DNA and RNA by in situ hybridization.

Using cloned restriction endonuclease fragments of Herpes simplex virus (HSV), human papillomavirus (HPV), and cytomegalovirus (CMV) DNA as probes, viral DNA and RNA sequences have been detected in human tissues. The probes were labeled either with a radioactive isotope, for subsequent detection by autoradiography, or with biotin. This latter technique has been successfully used to visualize HPV DNA in tissues that have been fixed in formalin and embedded in paraffin, and is therefore of value in retrospective studies of histological specimens. HPV DNA was detected under non-stringent conditions (Tm = -42 degrees C) with heterologous probes in plantar and common warts, laryngeal papillomas, and anogenital condylomas. The specific type of HPV was established using stringent hybridization conditions (Tm = - 17 degrees C). Results from these and from malignant tissues show the distribution and localization of HSV and HPV RNA and DNA sequences in malignancies of squamous cell origin in the anogenital region. Both HSV and HPV DNA sequences have occasionally been detected in the same tumor, providing a further impetus to test the hypothesis that an initiator-promoter relationship might involve these common human viruses in the development of some tumors.

Base Sequence↗
PubMed1985

Genetic heterogeneity of the human papovaviruses BK and JC.

We have examined the structure and infectivity of BKV and JCV genomes from prototype strains after cell culture passage and of BKV genomes from primary isolates. Genomic structures were determined by restriction endonuclease analysis of molecularly cloned DNA. Infectivity was determined by transfection of the cloned genomes into urine-derived epithelial cells and assaying for viral proteins and virus production. Prototype BKV DNA, which was cloned after 14 passages in three different cell lines, contained no alterations in restriction enzyme sites and was infectious. In contrast, prototype JCV acquired changes in the late region of the genome during passage in cell culture and the cloned DNA was not infectious. Urine-derived cells were used to isolate virus from the urine of two renal transplant patients and one asymptomatic individual. The genome of the virus isolated from the normal individual was indistinguishable from prototype BKV except for a 60-base pair deletion, which was localized between 0.62 and 0.72 map units. Two isolates from transplant patients differed from each other and from prototype BKV at a number of restriction enzyme cleavage sites located in the early region and were infectious. Genomes containing deletions from 100 to 600 base pairs were also cloned but were not infectious.

Chromosome Mapping↗
PubMed1985

Direct detection of the human papovavirus BK in urine of bone marrow transplant recipients: comparison of DNA hybridization with ELISA.

Urine specimens from bone marrow transplant (BMT) recipients and from controls were directly tested for BK virus (BKV) DNA sequences by dot hybridization and for BKV antigen by a double-antibody indirect ELISA. A total of 158 specimens from 55 BMT patients (57 collected prior to or at the time of transplantation and 101 in the posttransplant period) and single urines from 125 control subjects were examined by both methods. A molecularly cloned, 32P-labelled BKV probe was hybridized with urine sediments that were spotted directly on nitrocellulose filters and denatured in situ. BKV DNA sequences were detected in 1 (1.8%) pretransplant and 22 (21.8%) posttransplant urines of BMT patients, and in none of control urines. In ELISA of urine supernatants, BKV antigen was detected in 1 (1.8%) pretransplant and 21 (20.8%) posttransplant urines of BMT patients and in 1 (0.8%) of the control urines. The results of the two tests correlated as follows: 16 urines were positive and 253 urines negative by both methods; seven specimens were positive by DNA hybridization only and seven were positive by ELISA alone. Virus excretion in urine was demonstrated in 20 (36.4%) patients by DNA hybridization, in 19 (34.5%) patients by ELISA, in 15 (27.3%) patients by both methods, and in 24 (44%) patients by at least one of the two tests.

Adolescent↗
PubMed1985

Detection and localization of human papillomavirus DNA in human genital condylomas by in situ hybridization with biotinylated probes.

We have examined the distribution of human papillomavirus (HPV) DNA in paraffin sections of humans warts by in situ hybridization with biotin-labeled DNA probes. Recombinant plasmid DNAs (HPV-1, -6, -11, -16) were labeled by nick translation with biotinylated deoxyuridine triphosphate. Paraffin sections were hybridized with the probes for 18 h in stringent or non-stringent conditions, and DNA-DNA hybrids were detected by immunocytochemistry. Paraffin sections of warts were also examined for the presence of HPV capsid antigen with the avidin-biotin peroxidase complex method for immunocytochemistry. HPV DNA was detected and localized in paraffin sections from a plantar wart, a laryngeal papilloma, and seven anogenital condylomas. The specific HPV type present in each lesion was determined by hybridization under stringent conditions with the homologous DNA probe. The papillomas were found to contain many more cells with replicating virus DNA, as demonstrated by in situ hybridization, than was apparent from the number of cells containing detectable virus antigen. In situ hybridization with biotin-labeled probes is an effective technique for the identification of HPV infection in routinely collected and processed tissue specimens.

Antigens, Neoplasm↗
PubMed1984

HSV, CMV, and HPV in human neoplasia.

We are studying the role of sexually transmitted viruses in the development of human tumors. The persistence of herpes simplex virus, cytomegalovirus, and human papillomavirus nucleic acid sequences has been examined using cloned viral DNA sequences as probes. The relationship of the viruses to various stages in the progression of neoplasia is examined, with particular reference to the role of viral and/or cellular genes in the initiation, promotion, and maintenance of the neoplastic phenotype. The human tumors of major interest in this context are carcinomas of the cervix, vulva, and anus and Kaposi's sarcoma. The minimal fragment of HSV-2 DNA detected in cervical tumors is contained within a 656-bp sequence that can be used in transfection experiments to transform rodent cells in vitro to a malignant phenotype. However, neither this fragment nor any other is consistently retained in cervical tumors, suggesting that this viral DNA may initiate but not maintain the transformed phenotype.

Carcinoma↗