Dataset Information

Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type.

ABSTRACT: The association between human papillomavirus (HPV) DNA copy number and cervical disease was investigated. Viral DNA copy number for the most common high-risk HPV types in cervical cancer (types 16, 18, 31, and 45) was determined in cervical cytobrush specimens from 149 women with high-grade cervical intraepithelial neoplasias (CIN II-CIN III), 176 with low-grade CIN (CIN I), and 270 with normal cytology. Quantitative, PCR-based fluorescent assays for each of the HPV genotypes and for the beta-globin gene were used. The amount of cellular DNA increased significantly with increasing disease; thus, HPV was expressed as copies per microgram of cellular DNA. The assay had a dynamic range of >10(7), allowing documentation for the first time of the wide range of HPV copy numbers seen in clinical specimens. Median HPV DNA copy number varied by more than 10(4) among the viral types. HPV16 was present in the highest copy number; over 55% of HPV16-positive samples contained more than 10(8) copies/microgram. Median copy number for HPV16 showed dramatic increases with increasing epithelial abnormality, an effect not seen with the other HPV types. HPV16 increased from a median of 2.2 x 10(7) in patients with normal cytology, to 4.1 x 10(7) in CIN I patients, to 1.3 x 10(9) copies/microgram in CIN II-III patients. Even when stratified by cervical disease and viral type, the range of viral DNA copies per microgram of cellular DNA was quite large, precluding setting a clinically significant cutoff value for "high" copy numbers predictive of disease. This study suggests that the clinical usefulness of HPV quantitation requires reassessment and is assay dependent.

SUBMITTER: Swan DC

PROVIDER: S-EPMC88645 | biostudies-literature | 1999 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type.

Swan D C DC Tucker R A RA Tortolero-Luna G G Mitchell M F MF Wideroff L L Unger E R ER Nisenbaum R A RA Reeves W C WC Icenogle J P JP

Journal of clinical microbiology 19990401 4

The association between human papillomavirus (HPV) DNA copy number and cervical disease was investigated. Viral DNA copy number for the most common high-risk HPV types in cervical cancer (types 16, 18, 31, and 45) was determined in cervical cytobrush specimens from 149 women with high-grade cervical intraepithelial neoplasias (CIN II-CIN III), 176 with low-grade CIN (CIN I), and 270 with normal cytology. Quantitative, PCR-based fluorescent assays for each of the HPV genotypes and for the beta-gl ...[more]

PMID: 10074522

Similar Datasets

Project description:BACKGROUND: The national Human Papillomavirus (HPV) Immunisation Programme in New Zealand was introduced in 2008, and involves routine vaccination of girls 12-13 years with a catch-up for females aged up to 19 years. The aims of this study were to measure the pre-vaccination prevalence of oncogenic HPV infection in women aged 20-69 years who were participating in the New Zealand National Cervical Screening Programme (NZ-NCSP) and who were: (1) referred with high grade cytology with a subsequent histologically-confirmed high grade cervical intraepithelial neoplasia (CIN2/3) or adenocarcinoma in situ (AIS); or (2) were in the wider group of women who had a cytological prediction of high grade squamous disease or glandular abnormality (ASC-H/ HSIL+/AGC/AIS). METHODS: Women aged 20-69 years appearing on the NZ-NCSP register between August 2009-February 2011 with a cytology record of ASC-H/HSIL+/AGC/AIS were invited to participate in the study. Liquid-based cytology specimens were tested for 37 HPV types using Linear Array genotyping. The prevalence of type-specific HPV infection was reported within women with histologically-confirmed CIN 2/3 and within the wider group with ASC-H/HSIL+/AGC/AIS cytology. Age-specific trends for the relative proportion of HPV 16/18 vs. other oncogenic types in CIN2/3 were assessed. RESULTS: A total of 594 women with ASC-H/HSIL+/AGC/AIS cytology and a valid HPV test were recruited; of these 356 (60%) had confirmed CIN2/3 and 6 (1%) had confirmed AIS or glandular dysplasia. Positivity rates for any oncogenic HPV infection and for HPV16 and/or 18 within confirmed CIN2/3-AIS were 95% (95%CI: 92-97%) and 60% (54-65%) respectively; in all women with ASC-H/HSIL+/AGC/AIS cytology it was 87% (84-89%) and 53% (49-57%), respectively. The most common reported HPV types in women with CIN 2/3 were 16 (51%), 52 (19%), 31 (17%), 33 (13%) and 18 (12%). A trend for higher rates of HPV 16/18 infection compared to other oncogenic types was observed in younger women (p=0.0006). CONCLUSIONS: The prevalence of HPV 16/18 in confirmed high grade disease in New Zealand is comparable to that observed in Australia and European countries. Test positivity rates for type 52 appear higher than in comparable studies in other developed countries. A greater proportion of high grade lesions in younger women appear to be associated with HPV 16/18 infection.

Project description:BACKGROUND: The development of cervical cancer and its high-grade precursor lesions (Cervical Intraepithelial Neoplasia grade 2/3 [CIN2/3]) result from a persistent infection with high-risk human papillomavirus (hrHPV) types and the accumulation of (epi)genetic host cell aberrations. Epidemiological studies have demonstrated variable CIN2/3 and cancer risks between different hrHPV types. Recent genomic profiling studies revealed substantial heterogeneity in the chromosomal aberrations detected in morphologically indistinguishable CIN2/3 suggestive of varying cancer risk. The current study aimed to investigate whether CIN2/3 with different hrHPV types vary with respect to their chromosomal profiles, both in terms of the number of aberrations and chromosomal loci affected. METHODS: Chromosomal profiles were determined of 43 p16INK4a-immunopositive CIN2/3 of women with long-term hrHPV infection (? 5 years). Sixteen lesions harboured HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52 and 2 HPV58. RESULTS: Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two major clusters, characterised by either few or multiple chromosomal aberrations, respectively. A majority of 87.5% of lesions with HPV16 were in the cluster with relatively few aberrations, whereas no such unbalanced distribution was seen for lesions harbouring other hrHPV types. Analysis of the two most prevalent types (HPV16 and HPV31) in this data set revealed a three-fold increase in the number of losses in lesions with HPV31 compared to HPV16-positive lesions. In particular, losses at chromosomes 2q, 4p, 4q, 6p, 6q, 8q & 17p and gain at 1p & 1q were significantly more frequent in HPV31-positive lesions (FDR < 0.2). CONCLUSIONS: Chromosomal aberrations in CIN2/3 are at least in part related to the hrHPV type present. The relatively low number of chromosomal aberrations observed in HPV16-positive CIN2/3 suggests that the development of these lesions is less dependent on genetic insult than those caused by other types like HPV31.

Project description:The availability of human papillomavirus (HPV) DNA testing and vaccination against HPV types 16 and 18 (HPV-16,18) motivates questions about the cost-effectiveness of cervical cancer prevention in the United States for unvaccinated older women and for girls eligible for vaccination.An empirically calibrated model was used to assess the quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (2004 US dollars per QALY) of screening, vaccination of preadolescent girls, and vaccination combined with screening. Screening varied by initiation age (18, 21, or 25 years), interval (every 1, 2, 3, or 5 years), and test (HPV DNA testing of cervical specimens or cytologic evaluation of cervical cells with a Pap test). Testing strategies included: 1) cytology followed by HPV DNA testing for equivocal cytologic results (cytology with HPV test triage); 2) HPV DNA testing followed by cytology for positive HPV DNA results (HPV test with cytology triage); and 3) combined HPV DNA testing and cytology. Strategies were permitted to switch once at age 25, 30, or 35 years.For unvaccinated women, triennial cytology with HPV test triage, beginning by age 21 years and switching to HPV testing with cytology triage at age 30 years, cost $78,000 per QALY compared with the next best strategy. For girls vaccinated before age 12 years, this same strategy, beginning at age 25 years and switching at age 35 years, cost $41,000 per QALY with screening every 5 years and $188,000 per QALY screening triennially, each compared with the next best strategy. These strategies were more effective and cost-effective than screening women of all ages with cytology alone or cytology with HPV triage annually or biennially.For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more cost-effective than current screening recommendations.

Project description:ImportanceMitochondrial dysfunction is a core component of the aging process and may play a key role in atherosclerotic cardiovascular disease. Mitochondrial DNA copy number (mtDNA-CN), which represents the number of mitochondria per cell and number of mitochondrial genomes per mitochondrion, is an indirect biomarker of mitochondrial function.ObjectiveTo determine whether mtDNA-CN, measured in an easily accessible tissue (buffy coat/circulating leukocytes), can improve risk classification for cardiovascular disease (CVD) and help guide initiation of statin therapy for primary prevention of CVD.Design, setting, and participantsProspective, population-based cohort analysis including 21?870 participants (20?163 free from CVD at baseline) from 3 studies: Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities Study (ARIC), and Multiethnic Study of Atherosclerosis (MESA). The mean follow-up was 13.5 years. The study included 11?153 participants from ARIC, 4830 from CHS, and 5887 from MESA. Analysis of the data was conducted from March 10, 2014, to January 29, 2017.ExposuresMitochondrial DNA-CN measured from buffy coat/circulating leukocytes.Main outcomes and measuresIncident CVD, which combines coronary heart disease, defined as the first incident myocardial infarction or death owing to coronary heart disease, and stroke, defined as the first nonfatal stroke or death owing to stroke.ResultsOf the 21?870 participants, the mean age was 62.4 years (ARIC, 57.9 years; MESA, 62.4 years; and CHS, 72.5 years), and 54.7% of participants were women. The hazard ratios for incident coronary heart disease, stroke, and CVD associated with a 1-SD decrease in mtDNA-CN were 1.29 (95% CI, 1.24-1.33), 1.11 (95% CI, 1.06-1.16), and 1.23 (95% CI, 1.19-1.26). The associations persisted after adjustment for traditional CVD risk factors. Addition of mtDNA-CN to the 2013 American College of Cardiology/American Heart Association Pooled Cohorts Equations for estimating 10-year hard atherosclerosis CVD risk was associated with improved risk classification (continuous net reclassification index, 0.194; 95% CI, 0.130-0.258; P?<?.001). Mitochondrial DNA-CN further improved sensitivity and specificity for the 2013 American College of Cardiology/American Heart Association recommendations on initiating statin therapy for primary prevention of ASCVD (net 221 individuals appropriately downclassified and net 15 individuals appropriately upclassified).Conclusions and relevanceMitochondrial DNA-CN was independently associated with incident CVD in 3 large prospective studies and may have potential clinical utility in improving CVD risk classification.

Dataset Information

Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type.

Publications

Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets