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Grant Details

Grant Number: 5R01CA084396-04 Interpret this number
Primary Investigator: Xi, Long
Organization: University Of Washington
Project Title: Epidemiology of Hpv16/18 Variants in Cervical Neoplasia
Fiscal Year: 2003
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Abstract

DESCRIPTION (Adapted from applicant's abstract): Human papillomaviruses (HPVs) are classified into "types," "subtypes," and variants." HPV16 and 18 are types known to be central to the pathogenesis of most invasive cervical cancers (ICC) and their precursor lesion, cervical intraepithelial neoplasia (CIN) grade 2-3. However, many women acquire and spontaneously resolve cervical infections with these HPV types. We hypothesize that certain HPV 1 6 and 18 variants differ in their biologic behavior and risk of cervical neoplasia. A number of small studies have examined associations between HPV 1 6 and 18 variants and risk of cervical neoplasia and many, but not all, suggest differences in biologic behaviors. Confirmation of these findings in large, more representative populations is essential. We propose to efficiently examine these issues by performing additional assays on a subset of samples collected during the ongoing NCI-sponsored, multi-center randomized clinical trial: ASCUS/LSIL Triage Study (ALTS). This study, which includes 5,086 women from four different regions of the country, is examining how to best manage women referred with a cytologic diagnosis of atypical squamous cells of uncertain significance (ASCUS) or low- grade squamous intraepithelial lesions (LSIL) of the cervix. The ALTS dataset is extremely rich with results from standardized collection and testing of clinical specimens, detailed questionnaires with information on potential confounders, and histologic and colposcopic diagnoses provided by expert panel review. By including data from only those women enrolled in the immediate colposcopy arm of ALTS, we will develop precise estimates of the association between HPV 1 6 and IS variants and cervical neoplasia (aims 1 and 2), and determine whether those variants that are associated with CIN 2-3 have increased DNA levels or specific nucleotide changes in the LCR and E6 regions of the genome (aim 4). Furthermore, using data from women enrolled in the immediate colposcopy and conservative management arms, we will provide the first observations on the relationship between HPV 1 6 variants and risk for recurrence after treatment for CIN 2-3 (aim 3). To address these aims, we will perform PCR-based assays for detection and typing of 7,290 samples, classify (by DNA sequencing) HPV variants present in samples from women infected with HPV16 (n=548) or 18 (n=222), and quantify (by a PCR-based kinetic thermocycling assay) the amount of HPV DNA present in the 1,915 HPV16-positive and 222 HPV18-positive samples. The proposed study is likely to make important contributions to our understanding of the role of HPV 16 and 18 variants in the pathogenesis of cervical cancer.

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Publications

Relationship between cigarette smoking and human papilloma virus types 16 and 18 DNA load.
Authors: Xi L.F. , Koutsky L.A. , Castle P.E. , Edelstein Z.R. , Meyers C. , Ho J. , Schiffman M. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Dec; 18(12), p. 3490-6.
PMID: 19959700
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Human Papillomavirus (HPV) type 16 and type 18 DNA Loads at Baseline and Persistence of Type-Specific Infection during a 2-year follow-up.
Authors: Xi L.F. , Hughes J.P. , Edelstein Z.R. , Kiviat N.B. , Koutsky L.A. , Mao C. , Ho J. , Schiffman M. .
Source: The Journal of infectious diseases, 2009-12-01; 200(11), p. 1789-97.
PMID: 19848609
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Identification of recombinant human papillomavirus type 16 variants.
Authors: Jiang M. , Xi L.F. , Edelstein Z.R. , Galloway D.A. , Olsem G.J. , Lin W.C. , Kiviat N.B. .
Source: Virology, 2009-11-10; 394(1), p. 8-11.
EPub date: 2009-09-15.
PMID: 19758676
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Human papillomavirus types 16 and 18 DNA load in relation to coexistence of other types, particularly those in the same species.
Authors: Xi L.F. , Edelstein Z.R. , Meyers C. , Ho J. , Cherne S.L. , Schiffman M. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Sep; 18(9), p. 2507-12.
EPub date: 2009-08-18.
PMID: 19690188
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Sequence variation of human papillomavirus type 16 and measurement of viral integration by quantitative PCR.
Authors: Jiang M. , Baseman J.G. , Koutsky L.A. , Feng Q. , Mao C. , Kiviat N.B. , Xi L.F. .
Source: Journal of clinical microbiology, 2009 Mar; 47(3), p. 521-6.
EPub date: 2008-12-30.
PMID: 19116350
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Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3.
Authors: Xi L.F. , Koutsky L.A. , Castle P.E. , Wheeler C.M. , Galloway D.A. , Mao C. , Ho J. , Kiviat N.B. .
Source: Journal of the National Cancer Institute, 2009-02-04; 101(3), p. 153-61.
EPub date: 2009-01-27.
PMID: 19176451
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Effect of cervical cytologic status on the association between human papillomavirus type 16 DNA load and the risk of cervical intraepithelial neoplasia grade 3.
Authors: Xi L.F. , Kiviat N.B. , Galloway D.A. , Zhou X.H. , Ho J. , Koutsky L.A. .
Source: The Journal of infectious diseases, 2008-08-01; 198(3), p. 324-31.
PMID: 18627250
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Risk of cervical intraepithelial neoplasia grade 2 or 3 after loop electrosurgical excision procedure associated with human papillomavirus type 16 variants.
Authors: Xi L.F. , Kiviat N.B. , Wheeler C.M. , Kreimer A. , Ho J. , Koutsky L.A. .
Source: The Journal of infectious diseases, 2007-05-01; 195(9), p. 1340-4.
EPub date: 2007-03-19.
PMID: 17397005
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Risk for high-grade cervical intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18.
Authors: Xi L.F. , Koutsky L.A. , Hildesheim A. , Galloway D.A. , Wheeler C.M. , Winer R.L. , Ho J. , Kiviat N.B. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2007 Jan; 16(1), p. 4-10.
PMID: 17220325
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Human papillomavirus type 16 and 18 variants: race-related distribution and persistence.
Authors: Xi L.F. , Kiviat N.B. , Hildesheim A. , Galloway D.A. , Wheeler C.M. , Ho J. , Koutsky L.A. .
Source: Journal of the National Cancer Institute, 2006-08-02; 98(15), p. 1045-52.
PMID: 16882941
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