Grant Number:	5R01AI032917-09 Interpret this number
Primary Investigator:	Wheeler, Cosette
Organization:	University Of New Mexico
Project Title:	Natural History Studies of HPV Infection
Fiscal Year:	1999

Because human papillomavirus (HPV) infections appear to be causally linked to most cervical intraepithelial neoplasia (CIN) and cervical carcinoma, it is important to identify determinants of HPV-associated cervical disease. A growing body of evidence suggests an important role for the major histocompatibility complex (MHC) in the etiology of cervical dysplasia and cancer. Further studies in this area are needed to determine the relationship between host-virus interaction and the risk for cervical disease. In addition to understanding host factors, we also need to understand the population dynamics of HPV infections. Currently, HPV "types" have been used as the exposure measure for HPV-associated risk for invasive cervical carcinoma. This level of exposure determination has not provided us with useful prognostic markers for determining risk of progression to invasive cervical carcinoma. Virtually no information is available concerning specific HPV sequences within HPV types associated with risk for invasive cervical carcinoma or presumed precursor lesions. Furthermore, sequence diversity of HPVs, the potential significance of HPV variants and subtypes, and relationships between HPV types have been given little consideration as factors important for determining risk for cervical disease. This grant application requests funding for studies that will examine host- and viral-specific risk factors of HPV-associated cervical disease. We have previously identified HPV-specific MHC associations with severe dysplasia/ClS and invasive cervical carcinoma in case-control studies of Hispanic women. We will characterize HLA class l and II loci in case-control studies of in situ and invasive cervical cancer in Hispanic and non-Hispanic white women from the same geographic location. We will also consider HPV sequence-specific risk factors for cervical disease. We have previously observed an amino acid change in the HPV-16 E6 open reading frame that is associated with high grade squamous intraepithelial lesions. We will examine this observation in a blinded investigation using specimens obtained through an ongoing longitudinal cohort study of HPV and cervical disease being conducted by the NCl. The proposed studies will form a basis for elucidating specific mechanisms of HPV-associated cervical cancer.




Human Papillomavirus Genotype Distributions: Implications For Vaccination And Cancer Screening In The United States
Authors: Wheeler C.M. , Hunt W.C. , Joste N.E. , Key C.R. , Quint W.G. , Castle P.E. .
Source: Journal Of The National Cancer Institute, 2009-04-01 00:00:00.0; 101(7), p. 475-87.
PMID: 19318628
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Variation In Hla Class I Antigen-processing Genes And Susceptibility To Human Papillomavirus Type 16-associated Cervical Cancer
Authors: Deshpande A. , Wheeler C.M. , Hunt W.C. , Peyton C.L. , White P.S. , Valdez Y.E. , Nolan J.P. .
Source: The Journal Of Infectious Diseases, 2008-02-01 00:00:00.0; 197(3), p. 371-81.
PMID: 18248301
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Human Papillomavirus Type 16 Integration In Cervical Carcinoma In Situ And In Invasive Cervical Cancer
Authors: Arias-Pulido H. , Peyton C.L. , Joste N.E. , Vargas H. , Wheeler C.M. .
Source: Journal Of Clinical Microbiology, 2006 May; 44(5), p. 1755-62.
PMID: 16672403
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Tnf-alpha Promoter Polymorphisms And Susceptibility To Human Papillomavirus 16-associated Cervical Cancer
Authors: Deshpande A. , Nolan J.P. , White P.S. , Valdez Y.E. , Hunt W.C. , Peyton C.L. , Wheeler C.M. .
Source: The Journal Of Infectious Diseases, 2005-03-15 00:00:00.0; 191(6), p. 969-76.
PMID: 15717274
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Specific Residues In Plasmatocyte-spreading Peptide Are Required For Receptor Binding And Functional Antagonism Of Insect Immune Cells
Authors: Clark K.D. , Garczynski S.F. , Arora A. , Crim J.W. , Strand M.R. .
Source: The Journal Of Biological Chemistry, 2004-08-06 00:00:00.0; 279(32), p. 33246-52.
PMID: 15192108
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Loss Of Heterozygosity On Chromosome 6 In Hpv-16 Positive Cervical Carcinomas Carrying The Drb1*1501-dqb1*0602 Haplotype
Authors: Arias-Pulido H. , Joste N. , Wheeler C.M. .
Source: Genes, Chromosomes & Cancer, 2004 Aug; 40(4), p. 277-84.
PMID: 15188450
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Priming Of Human Papillomavirus Type 11-specific Humoral And Cellular Immune Responses In College-aged Women With A Virus-like Particle Vaccine
Authors: Emeny R.T. , Wheeler C.M. , Jansen K.U. , Hunt W.C. , Fu T.M. , Smith J.F. , MacMullen S. , Esser M.T. , Paliard X. .
Source: Journal Of Virology, 2002 Aug; 76(15), p. 7832-42.
PMID: 12097595
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Human leukocyte antigen class I and II alleles and risk of cervical neoplasia: results from a population-based study in Costa Rica.
Authors: Wang S.S. , Wheeler C.M. , Hildesheim A. , Schiffman M. , Herrero R. , Bratti M.C. , Sherman M.E. , Alfaro M. , Hutchinson M.L. , Morales J. , et al. .
Source: The Journal Of Infectious Diseases, 2001-11-15 00:00:00.0; 184(10), p. 1310-4.
EPub date: 2001-11-15 00:00:00.0.
PMID: 11679920
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N-terminal Residues Of Plasmatocyte-spreading Peptide Possess Specific Determinants Required For Biological Activity
Authors: Clark K.D. , Volkman B.F. , Thoetkiattikul H. , Hayakawa Y. , Strand M.R. .
Source: The Journal Of Biological Chemistry, 2001-10-05 00:00:00.0; 276(40), p. 37431-5.
PMID: 11432871
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Determinants Of Genital Human Papillomavirus Detection In A Us Population
Authors: Peyton C.L. , Gravitt P.E. , Hunt W.C. , Hundley R.S. , Zhao M. , Apple R.J. , Wheeler C.M. .
Source: The Journal Of Infectious Diseases, 2001-06-01 00:00:00.0; 183(11), p. 1554-64.
PMID: 11343204
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Alanine-scanning Mutagenesis Of Plasmatocyte Spreading Peptide Identifies Critical Residues For Biological Activity
Authors: Clark K.D. , Volkman B.F. , Thoetkiattikul H. , King D. , Hayakawa Y. , Strand M.R. .
Source: The Journal Of Biological Chemistry, 2001-05-25 00:00:00.0; 276(21), p. 18491-6.
PMID: 11279096
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Human Papillomavirus: A Highly Prevalent Sexually Transmitted Disease Agent Among Female Sex Workers From Mexico City
Authors: Juárez-Figueroa L.A. , Wheeler C.M. , Uribe-Salas F.J. , Conde-Glez C.J. , Zampilpa-Mejía L.G. , García-Cisneros S. , Hernández-Avila M. .
Source: Sexually Transmitted Diseases, 2001 Mar; 28(3), p. 125-30.
PMID: 11289192
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Sequence Analysis Of The Long Control Region Of Human Papillomavirus Type 16 Variants And Functional Consequences For P97 Promoter Activity
Authors: Kämmer C. , Warthorst U. , Torrez-Martinez N. , Wheeler C.M. , Pfister H. .
Source: The Journal Of General Virology, 2000 Aug; 81(Pt 8), p. 1975-81.
PMID: 10900036
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Hematopoiesis In Larval Pseudoplusia Includens And Spodoptera Frugiperda
Authors: Gardiner E.M. , Strand M.R. .
Source: Archives Of Insect Biochemistry And Physiology, 2000 Apr; 43(4), p. 147-64.
PMID: 10737919
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Comparison Of Variant-specific Hybridization And Single-strand Conformational Polymorphism Methods For Detection Of Mixed Human Papillomavirus Type 16 Variant Infections
Authors: Emeny R.T. , Herron J.R. , Xi L.F. , Koutsky L.A. , Kiviat N.B. , Wheeler C.M. .
Source: Journal Of Clinical Microbiology, 1999 Nov; 37(11), p. 3627-33.
PMID: 10523565
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Plasmatocyte Spreading Peptide Induces Spreading Of Plasmatocytes But Represses Spreading Of Granulocytes
Authors: Strand M.R. , Clark K.D. .
Source: Archives Of Insect Biochemistry And Physiology, 1999 Nov; 42(3), p. 213-23.
PMID: 10536049
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Structure Of The Insect Cytokine Peptide Plasmatocyte-spreading Peptide 1 From Pseudoplusia Includens
Authors: Volkman B.F. , Anderson M.E. , Clark K.D. , Hayakawa Y. , Strand M.R. , Markley J.L. .
Source: The Journal Of Biological Chemistry, 1999-02-19 00:00:00.0; 274(8), p. 4493-6.
PMID: 9988679
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Genotyping Of 27 Human Papillomavirus Types By Using L1 Consensus Pcr Products By A Single-hybridization, Reverse Line Blot Detection Method
Authors: Gravitt P.E. , Peyton C.L. , Apple R.J. , Wheeler C.M. .
Source: Journal Of Clinical Microbiology, 1998 Oct; 36(10), p. 3020-7.
PMID: 9738060
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Plasmatocyte Spreading Peptide Is Encoded By An Mrna Differentially Expressed In Tissues Of The Moth Pseudoplusia Includens
Authors: Clark K.D. , Witherell A. , Strand M.R. .
Source: Biochemical And Biophysical Research Communications, 1998-09-18 00:00:00.0; 250(2), p. 479-85.
PMID: 9753657
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Risk Of Anal Carcinoma In Situ In Relation To Human Papillomavirus Type 16 Variants
Authors: Xi L.F. , Critchlow C.W. , Wheeler C.M. , Koutsky L.A. , Galloway D.A. , Kuypers J. , Hughes J.P. , Hawes S.E. , Surawicz C. , Goldbaum G. , et al. .
Source: Cancer Research, 1998-09-01 00:00:00.0; 58(17), p. 3839-44.
PMID: 9731493
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Isolation And Identification Of A Plasmatocyte-spreading Peptide From The Hemolymph Of The Lepidopteran Insect Pseudoplusia Includens
Authors: Clark K.D. , Pech L.L. , Strand M.R. .
Source: The Journal Of Biological Chemistry, 1997-09-12 00:00:00.0; 272(37), p. 23440-7.
PMID: 9287360
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Genomic Variation Of Human Papillomavirus Type 16 And Risk For High Grade Cervical Intraepithelial Neoplasia
Authors: Xi L.F. , Koutsky L.A. , Galloway D.A. , Kuypers J. , Hughes J.P. , Wheeler C.M. , Holmes K.K. , Kiviat N.B. .
Source: Journal Of The National Cancer Institute, 1997-06-04 00:00:00.0; 89(11), p. 796-802.
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Human Papillomavirus Type 16 Sequence Variation In Cervical Cancers: A Worldwide Perspective
Authors: Yamada T. , Manos M.M. , Peto J. , Greer C.E. , Munoz N. , Bosch F.X. , Wheeler C.M. .
Source: Journal Of Virology, 1997 Mar; 71(3), p. 2463-72.
PMID: 9032384
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Human Papillomavirus Type 16 Sequence Variants: Identification By E6 And L1 Lineage-specific Hybridization
Authors: Wheeler C.M. , Yamada T. , Hildesheim A. , Jenison S.A. .
Source: Journal Of Clinical Microbiology, 1997 Jan; 35(1), p. 11-9.
PMID: 8968874
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Intratype Variation In 12 Human Papillomavirus Types: A Worldwide Perspective
Authors: Stewart A.C. , Eriksson A.M. , Manos M.M. , Muñoz N. , Bosch F.X. , Peto J. , Wheeler C.M. .
Source: Journal Of Virology, 1996 May; 70(5), p. 3127-36.
PMID: 8627792
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Human Papillomavirus Type 16 Variant Lineages In United States Populations Characterized By Nucleotide Sequence Analysis Of The E6, L2, And L1 Coding Segments
Authors: Yamada T. , Wheeler C.M. , Halpern A.L. , Stewart A.C. , Hildesheim A. , Jenison S.A. .
Source: Journal Of Virology, 1995 Dec; 69(12), p. 7743-53.
PMID: 7494284
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Comparison Of Human Leukocyte Antigen Dr-dq Disease Associations Found With Cervical Dysplasia And Invasive Cervical Carcinoma
Authors: Apple R.J. , Becker T.M. , Wheeler C.M. , Erlich H.A. .
Source: Journal Of The National Cancer Institute, 1995-03-15 00:00:00.0; 87(6), p. 427-36.
PMID: 7861462
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Identification And Assessment Of Known And Novel Human Papillomaviruses By Polymerase Chain Reaction Amplification, Restriction Fragment Length Polymorphisms, Nucleotide Sequence, And Phylogenetic Algorithms
Authors: Bernard H.U. , Chan S.Y. , Manos M.M. , Ong C.K. , Villa L.L. , Delius H. , Peyton C.L. , Bauer H.M. , Wheeler C.M. .
Source: The Journal Of Infectious Diseases, 1994 Nov; 170(5), p. 1077-85.
PMID: 7963696
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Identification Of Five Novel Human Papillomavirus Sequences In The New Mexico Triethnic Population
Authors: Peyton C.L. , Wheeler C.M. .
Source: The Journal Of Infectious Diseases, 1994 Nov; 170(5), p. 1089-92.
PMID: 7963698
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A Novel Human Papillomavirus Sequence From An International Cervical Cancer Study
Authors: Peyton C.L. , Jansen A.M. , Wheeler C.M. , Stewart A.C. , Peto J. , Bosch F.X. , Muñoz N. , Teyssie A.R. , Torroella M. , Wabinga H.R. .
Source: The Journal Of Infectious Diseases, 1994 Nov; 170(5), p. 1093-5.
PMID: 7963699
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Epidemiology And Partial Nucleotide Sequence Of Four Novel Genital Human Papillomaviruses
Authors: Manos M.M. , Waldman J. , Zhang T.Y. , Greer C.E. , Eichinger G. , Schiffman M.H. , Wheeler C.M. .
Source: The Journal Of Infectious Diseases, 1994 Nov; 170(5), p. 1096-9.
PMID: 7963700
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