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M M Manos

Publications and source records attributed to M M Manos.

At least 37 records · Page 2Linked to original sources

Intratype variation in 12 human papillomavirus types: a worldwide perspective.

In this study, we have examined intratype human papillomavirus (HPV) sequence variation in a worldwide collection of cervical specimens. Twelve different HPV types including HPV-18, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51, HPV-52, HPV-58, HPV-59, HPV-68 (ME180), MM9/PAP238A (recently designated HPV-73), and a novel partial genomic HPV sequence designated MM4/Wl3B were analyzed in this study. Cervical specimens were collected as part of epidemiological investigations conducted in New Mexico and an international study of invasive cervical cancer (IBSCC). Specimens from several countries including Argentina, Brazil, Bolivia, Benin, Cuba, Colombia, Chile, Germany, Mali, Panama, Paraguay, Spain, Algeria, Uganda, Guinea, Tanzania, Indonesia, Philippines, Thailand, and the United States were evaluated. Specimen DNAs were subjected to amplification with the MY09/11 L1 consensus PCR system. The PCR products were cloned, and an approximately 410-bp region in the L1 open reading frame was sequenced from 146 specimens (approximately 60,000 bp). Within a single HPV type, nucleotide diversity varied between 0.2 and 2.9% (i.e., between any pair of variants) and the majority of nucleotide changes were synonymous (amino acid conserving). These data provide information pertinent to HPV diagnostic probe development and are potentially relevant to future rational vaccine strategies. Similarly, amino acid diversity varied between 0 and 5.1%. Some of these amino acid changes may represent markers of intertype evolutionary relationships. Presuming that HPVs have evolved under the same constraints as their corresponding hosts, the limited genetic diversity observed for all HPVs studied to date may reflect an evolutionary bottleneck occurring in both virus and host populations.

Amino Acid Sequence↗

Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group.

BACKGROUND: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. PURPOSE: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. METHODS: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. RESULTS: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). CONCLUSIONS: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. IMPLICATION: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.

Adult↗

Evaluation of seroreactivity to human papillomavirus type 16 virus-like particles in an incident case-control study of cervical neoplasia.

An ELISA to detect serum IgG antibody response to human papillomavirus (HPV) type 16 virus-like particles (VLPs) was evaluated in a case-control study of cervical neoplasia, nested within a prospective cohort study. Subjects included 688 controls with continued normal cytology and 152 cases with confirmed incident squamous intraepithelial lesions who were tested for DNA for a broad spectrum of HPV types at cohort and follow-up of controls, 16.6% were seropositive compared with 30.8% and 52.4% of cases with low- and high-grade lesions, respectively. Of HPV-16 DNA-negative subjects, 16.5% were seropositive. Seropositivity increased from 22.2% in subjects who were HPV-16 DNA-positive by polymerase chain reaction once only (enrollment or follow-up) to 83.3% in those who were HPV-16 DNA-positive at both time points. These data imply that serum antibody to HPV-16 VLPs is a relatively sensitive indicator of persisting cervical HPV-16 infection.

Antibodies, Viral↗

Accuracy and interlaboratory reliability of human papillomavirus DNA testing by hybrid capture.

Epidemiologists and clinicians wishing to introduce human papillomavirus (HPV) testing into cervical cancer prevention programs need standardized, reliable, and accurate HPV DNA tests that can detect the full spectrum of pathogenic HPV types. The Hybrid Capture System assay from Digene (hybrid capture assay) is a nonradioactive kit designed to detect 14 HPV types in two groups: a mix of 9 high-risk types associated with anogenital cancer (HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56) and another group of 5 low-risk types associated with condyloma acuminatum (HPV types 6, 11, 42, 43, and 44). The assay yields quantitative data meant to reflect viral concentration. In a study of 199 cervical specimens from women with concurrent Pap smears, we assessed the reliability of the new assay by comparing the hybrid capture assay results from three laboratories. We assessed the accuracy of the hybrid capture assay in comparison with a reference standard of HPV DNA content (multiple testing by several methods in two reference laboratories). We also compared the hybrid capture assay results with the concurrent cytologic diagnoses on the basis of an independent review of each smear by five pathologists. Pairwise interlaboratory agreement rates on HPV positivity for either high-risk or low-risk types ranged from 87 to 94%, and kappa values ranged from 0.61 to 0.83. Among specimens positive for high-risk types (the most important clinical outcome), the interlaboratory correlations of the quantitative data ranged from 0.60 to 0.90. Test results from all three laboratories were strongly associated with those of the HPV DNA reference standard and with the concurrent cytopathologic diagnoses. The most common errors were sporadic, apparently false-positive results.

Cervix Uteri↗

HLA DR-DQ associations with cervical carcinoma show papillomavirus-type specificity.

Cervical carcinoma is now known to be associated with human papillomaviruses (HPV), but the evidence for a link with specific HLA loci is controversial. The role of genetic variation at the HLA class II loci and among HPV types in cervical carcinoma was investigated by PCR DNA amplification and oligonucleotide probe typing of paraffin-embedded invasive cervical cancer tissue from Hispanic patients and of cervical swabs from Hispanic controls. Certain HLA class II haplotypes (such as DRB1*1501-DQB1*0602) were associated significantly, while DR13 haplotypes were negatively associated with cervical carcinoma. These associations are HPV16-type specific. These results suggest that specific HLA class II haplotypes may influence the immune response to specific HPV-encoded epitopes and affect the risk of cervical neoplasia.

Adenocarcinoma↗

Toward objective quality assurance in cervical cytopathology. Correlation of cytopathologic diagnoses with detection of high-risk human papillomavirus types.

Using The Bethesda System, five pathologists independently diagnosed 200 smears that originally had been classified as "atypical," and the results were correlated with concurrent detection of human papillomavirus (HPV) DNA by Southern analysis and by polymerase chain reaction amplification. The smears were reclassified as benign reactive changes (negative), atypical squamous cells of undetermined significance, or squamous intraepithelial lesion (SIL). Exact five-way cytologic agreement was achieved in only 29% of smears, and no slide was diagnosed as atypical squamous cells of undetermined significance by all reviewers. The detection of high-risk types of HPV correlated strongly with the likelihood of a diagnosis of squamous intraepithelial lesion. High-risk HPV types were detected in approximately 60% of smears reclassified as squamous intraepithelial lesion compared with 30% of those reclassified as atypical squamous cells of undetermined significance and 10% of negative smears (P < .001). Every smear unanimously diagnosed by the panel as squamous intraepithelial lesion was associated with detectable HPV DNA, mainly of high-risk types. Low-risk HPV DNA types were found with similar frequency in all diagnostic categories assigned by the reviewers. Based on the consistent relation between high-risk HPV detection and diagnoses according to the Bethesda System, the authors conclude that HPV testing may have an important role in quality assurance in cervical cytopathology.

Blotting, Southern↗

Identification and assessment of known and novel human papillomaviruses by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence, and phylogenetic algorithms.

The identification and taxonomy of papillomaviruses has become increasingly complex, as approximately 70 human papillomavirus (HPV) types have been described and novel HPV genomes continue to be identified. Methods and corresponding DNA sequence data bases were designed for the reliable identification of mucosal HPV genomes from clinical specimens. HPVs are identified by the amplification of a fragment of the L1 region by consensus primer polymerase chain reaction (PCR) and subsequent hybridization or restriction fragment length polymorphism analysis. L1 PCR fragments may be further characterized by nucleotide sequencing. Conservation of 30 (of 151) predicted amino acids identifies HPV genomic fragments, and nucleotide sequence alignments allow calculation of their phylogenetic relatedness. Sequence differences > 10% from any known HPV type suggest a novel HPV type. Phylogenetic relationships with known HPV types may permit predictions of biology. With these criteria, 10 PCR fragments were identified that would qualify as new genital HPV types after complete genomic isolation.

Amino Acid Sequence↗

Epidemiology and partial nucleotide sequence of four novel genital human papillomaviruses.

Polymerase chain reaction (PCR)-based genital human papillomavirus (HPV) detection methods that use consensus primers have enabled the broad-spectrum detection of most characterized HPV types. In addition, these techniques have allowed the identification of potentially novel viral sequences in clinical specimens. These methods were used to determine the partial L1 nucleotide sequence (the region generated by L1 consensus primers MY09 and MY11) of four novel viruses. The prevalence of these viruses in cytologically normal and dysplastic cervical specimens and in invasive cervical cancer was also determined. The partial DNA sequences of W13B (MM4), PAP291 (MM7), PAP155 (MM8), and PAP238a (MM9) are most similar to HPV-51, -61, -61, and -34, respectively. Prevalence studies suggest that W13B and PAP238a are cancer-associated, while PAP155 and PAP291 appear to be lower-risk viruses.

Base Sequence↗

Multiple Bowen's disease of the fingers associated with human papilloma virus type 16.

BACKGROUND: The occurrence of multiple Bowen's disease (BD) in skin away from the anogenital area is rare. In contrast, multiple lesions of BD involving the anogenital skin (bowenoid papulosis) are not so rare and have been found to associated with human papilloma virus (HPV) usually type 16. We encountered a patient with multiple BD of the fingers and endeavored to detect HPV in his lesions. METHODS: Separate BD lesions from 3 fingers of the patient were investigated for the presence of HPV by means of the polymerase chain reaction, followed by dot blot hybridization. Other cases of BD with coexistent hpv infection excluding the anogenital area were collected from the literature for comparative study. RESULTS: HPV type 16 was detected in each of the three finger lesions of BD. Twenty cases of HPV related BD involving sites other than the anogenital area were found in the literature. Three of these cases had multiple lesions. CONCLUSIONS: Review of the 4 cases with multiple HPV related nonanogenital BD and the 17 others with solitary lesions reveals predilection for the hands and feet (90%) and affinity for type 16 infection (81%). The lesions usually present as verrucous plaques.

Adult↗

Comparison of dot filter hybridization, Southern transfer hybridization, and polymerase chain reaction amplification for diagnosis of anal human papillomavirus infection.

The detection and classification of human papillomavirus (HPV) by a consensus primer polymerase chain reaction (PCR) technique were compared with detection and classification by dot filter hybridization (DFH) and Southern transfer hybridization (STH). PCR detected HPV in 87% of specimens; the detection rates for DFH and STH were 51% and 49%, respectively. The specific HPV types detected by STH were also detected by PCR in 90% of specimens. However, 75% of the samples positive for unclassified HPV by STH were typed by PCR. PCR results were reproducible, as assessed by repeat analysis (96% agreement), by analysis of paired same-day specimens (89% agreement), and by interlaboratory analysis (88% agreement). PCR is a sensitive, specific, and reproducible test for HPV detection and classification in clinical and epidemiologic studies.

Anus Diseases↗

Papillomavirus found in anorectal squamous carcinoma, not in colon adenocarcinoma.

We used polymerase chain reaction DNA amplification methods for the detection and typing of genital human papillomaviruses in paraffin-embedded tissue sections of five patients with anorectal squamous cell carcinoma and 22 patients with colonic adenocarcinoma. The cases were further tested by in situ hybridization with biotin-labeled probes specific for human papillomavirus types 6/11, 16/18, and 31/33/35. By polymerase chain reaction, human papillomavirus DNA was demonstrated in all of the cases of anorectal squamous cell carcinoma and in none of the cases of colonic adenocarcinoma for which analyzable DNA was available. Tumor cell nuclei stained for human papillomavirus DNA by in situ hybridization in four of the five cases of squamous cell carcinoma and in none of the cases of colonic adenocarcinoma. We conclude that human papillomavirus types usually associated with malignant transformation are uniformly present in anorectal squamous cell carcinoma but are absent from adenocarcinoma of the colon.

Adenocarcinoma↗

Polymerase chain reaction-based methods for the detection of human papillomavirus DNA.

The unprecedented sensitivity of the polymerase chain reaction (PCR) DNA amplification technology provides numerous advantages for the detection of human papillomavirus (HPV) DNA. In this chapter, the principles of the method and its advantages are discussed; disadvantages of the technology and proposed solutions are also presented. To accommodate the complexity of the many distinct HPV types, both type-specific and consensus PCR-based detection methods have evolved. Consensus primer systems, which afford the amplification of a broad spectrum of HPV types, have proven particularly useful in epidemiological studies and in novel virus identification. Since the introduction of PCR into the HPV field, there have been rapid advances and improvements PCR technology. However, standardization of PCR methods for HPV detection is essential for research to fully benefit from the technology. To that end, specific guidelines regarding experimental controls, assessment of analytic sensitivity and data interpretation are outlined here.

DNA, Viral↗

Determinants of genital human papillomavirus infection in young women.

Carcinoma of the cervix has several well-established epidemiologic risk factors, including multiple sexual partners and early age at first intercourse. Human papillomavirus (HPV) infection appears to have an etiologic role in the development of cervical neoplasia, but evidence linking HPV infection to known risk factors for cervical cancer has been inconsistent. The lack of expected correlations may be due to the inaccuracy of HPV assays previously used. A polymerase chain reaction DNA amplification method for the detection of HPV was used to investigate the determinants of genital HPV infection in a cross-sectional sample of 467 women attending a university health service. In contrast to studies using less accurate detection methods, the risk factors for HPV infection found here were consistent with those for cervical neoplasia. The risk of HPV infection was strongly and independently associated with increasing numbers of sexual partners in a lifetime, use of oral contraceptives, younger age, and black race. Age at first intercourse, smoking, and history of a prior sexually transmitted disease were correlated with, but not independently predictive of, HPV infection. These results demonstrate that the key risk factors for cervical carcinoma are strongly associated with genital HPV infection. This correlation suggests that HPV has an etiologic role in cervical neoplasia and reaffirms the sexual route of HPV transmission.

Adolescent↗

PCR amplification from paraffin-embedded tissues. Effects of fixative and fixation time.

The polymerase chain reaction (PCR) DNA amplification method is a powerful new tool for the retrospective analysis of paraffin-embedded tissue (PET). The technique has afforded the sensitive and specific detection of nucleic acid sequences associated with genetic and infectious diseases. However, PET processing conditions vary in their suitability for amplification. The authors have examined the effects of 11 fixatives at three fixation times. The effect of fixation was measured by the ability of the DNA in a treated tissue to serve as a template for the amplification of DNA fragments that ranged from 110 to 1,327 base pairs in length. Specimens fixed in acetone or 10% buffered neutral formalin were found to be best suited for subsequent analysis by PCR. A second group of fixatives, including Zamboni's, Clarke's, paraformaldehyde, formalin-alcohol-acetic acid, and methacarn, compromised amplification efficiency. Tissues treated with Carnoy's, Zenker's, or Bouin's, respectively, were even less desirable for amplification analysis.

Acetone↗

PCR amplification from paraffin-embedded tissues: recommendations on fixatives for long-term storage and prospective studies.

The development of polymerase chain reaction (PCR) DNA amplification methods has afforded molecular studies of fixed paraffin-embedded tissue samples and other archival material. Some fixation methods damage DNA, and thus deleteriously affect subsequent PCR analysis. This study addressed the effect of short- and long-term storage (2 hr to 30 days) in a variety of fixatives (10% buffered-neutral formalin [BNF], 95% ethanol, acetone, and OmniFix) before paraffin embedding. We tested the ability of prepared tissue sections to yield DNA amplification products ranging from 268 to 1327 bp. Results indicated that tissues fixed for 8 days in BNF were able to amplify 536-bp but very little 989-bp DNA fragments; after 30 days of BNF fixation only a 268-bp fragment was amplifiable. Samples fixed in OmniFix and acetone yielded products of 989 and 1327 bp, respectively, after 8 days of fixation; both fixatives yielded 989-bp amplification products after 30 days of fixation. Tissues fixed in 95% ethanol for up to 30 days efficiently produced DNA amplification fragments of up to 1327 bp in length. The results provide important information for prospective studies that involve PCR analysis from archival material. Furthermore, fixation and long-term storage in ethanol should prove particularly useful in remote areas where refrigeration or immediate sample-processing is unavailable.

DNA↗