Grant Number:	5R01CA061197-03 Interpret this number
Primary Investigator:	Adami, Hans-Olov
Organization:	Karolinska Institute
Project Title:	HPV and Cervix Neoplasia-a Case Control Study
Fiscal Year:	1998

DESCRIPTION: (Adpated from the Applicant's Abstract): The applicants' objective is to advance the understanding of the role played by genital human papillomavirus (HPV) in the etiology of carcinoma in situ (CIS) -- and inferentially invasive cancer -- of the cervix. While a causal role of HPV is likely, no large population-based, prospective study has examined its role in the natural history from normal epithelium to CIS, nor the role of cell-mediated immunity (as determined by HLA haplotype), microheterogeneity (or mutations) in the HPV genome, or of other factors that may determine transience/persistence of HPV infection. Nor has the purported orderly progression or monoclonal origin of cervix neoplasia been established. They propose a broad, interdisciplinary case-control study, nested in a population-based cohort. This study uses unique Swedish opportunities for a stringent study base definition, long-term follow-up and retrieval of smears and histopathologic specimens; it has an extensive morphologic and molecular component. The main specific questions relate to 1) determinants of progression: long-term pattern of infection (transience, persistence, reinfection) by HPV type, concordance between HPV in smears and CIS lesions, microheterogeneity or acquired mutations in the HPV genome, effect modification by HLA haplotype and/or smoking; 2) progression and clonality: correlation between HPV and the morphology as well as mono- or polyclonality of concomitant lesions as indicated by x-chromosome inactivation. They will follow up through 1993 a population-based cohort of women whose first PAP smear after 1969 was normal. At least 400 incident cases of CIS and 400 matched controls will be included and subjected to a telephone interview. On average five sequential smears from each subject (a total of about 4,000 smears) will undergo DNA extraction and PCR-based analyses including typing of 19 HPV-types, and of HLA class II haplotypes (HLA-DQB1 and HLA-DRB1) in one smear per individual. Also, in a selected set (about 100 cases) sequencing of a proportion of the HPV genome will be performed to study microheterogeneity. Detailed studies of progression and clonality will be carried out; the specimens from about 50 cases of CIS with multiple discrete lesions will be microdissected, followed by DNA extraction and analysis of HPV as well as X-chromosome inactivation. These data will be used on a number of different analyses including conditional logistic regression.




Bereavement Is Associated with an Increased Risk of HPV Infection and Cervical Cancer: An Epidemiological Study in Sweden.
Authors: Lu D. , Sundström K. , Sparén P. , Fall K. , Sjölander A. , Dillner J. , Helm N.Y. , Adami H.O. , Valdimarsdóttir U. , Fang F. .
Source: Cancer Research, 2016-02-01 00:00:00.0; 76(3), p. 643-51.
EPub date: 2016-02-01 00:00:00.0.
PMID: 26634926
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HLA class II allele control of HPV load in carcinoma in situ of the cervix uteri.
Authors: Beskow A.H. , Moberg M. , Gyllensten U.B. .
Source: International Journal Of Cancer, 2005-11-10 00:00:00.0; 117(3), p. 510-4.
PMID: 15906352
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Host genetic control of HPV 16 titer in carcinoma in situ of the cervix uteri.
Authors: Beskow A.H. , Gyllensten U.B. .
Source: International Journal Of Cancer, 2002-10-20 00:00:00.0; 101(6), p. 526-31.
PMID: 12237892
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Clonality analysis of synchronous lesions of cervical carcinoma based on X chromosome inactivation polymorphism, human papillomavirus type 16 genome mutations, and loss of heterozygosity.
Authors: Hu X. , Pang T. , Asplund A. , Pontén J. , Nistér M. .
Source: The Journal Of Experimental Medicine, 2002-04-01 00:00:00.0; 195(7), p. 845-54.
PMID: 11927629
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Oncogene lineages of human papillomavirus type 16 E6, E7 and E5 in preinvasive and invasive cervical squamous cell carcinoma.
Authors: Hu X. , Pang T. , Guo Z. , Pontén J. , Nistér M. , Bernard Afink G. .
Source: The Journal Of Pathology, 2001 Oct; 195(3), p. 307-11.
PMID: 11673827
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HLA class II alleles associated with infection by HPV16 in cervical cancer in situ.
Authors: Beskow A.H. , Josefsson A.M. , Gyllensten U.B. .
Source: International Journal Of Cancer, 2001 Sep; 93(6), p. 817-22.
PMID: 11519043
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HPV16 E6 gene variations in invasive cervical squamous cell carcinoma and cancer in situ from Russian patients.
Authors: Hu X. , Pang T. , Guo Z. , Mazurenko N. , Kisseljov F. , Pontén J. , Nistér M. .
Source: British Journal Of Cancer, 2001-03-23 00:00:00.0; 84(6), p. 791-5.
PMID: 11259093
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Analysis of intratumoral heterogeneity of chromosome 3p deletions and genetic evidence of polyclonal origin of cervical squamous carcinoma.
Authors: Guo Z. , Wu F. , Asplund A. , Hu X. , Mazurenko N. , Kisseljov F. , Pontén J. , Wilander E. .
Source: Modern Pathology : An Official Journal Of The United States And Canadian Academy Of Pathology, Inc, 2001 Feb; 14(2), p. 54-61.
PMID: 11235906
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Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study.
Authors: Josefsson A.M. , Magnusson P.K. , Ylitalo N. , Sørensen P. , Qwarforth-Tubbin P. , Andersen P.K. , Melbye M. , Adami H.O. , Gyllensten U.B. .
Source: Lancet (london, England), 2000-06-24 00:00:00.0; 355(9222), p. 2189-93.
PMID: 10881891
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Clonality of precursors of cervical cancer and their genetical links to invasive cancer.
Authors: Guo Z. , Pontén F. , Wilander E. , Pontén J. .
Source: Modern Pathology : An Official Journal Of The United States And Canadian Academy Of Pathology, Inc, 2000 Jun; 13(6), p. 606-13.
PMID: 10874663
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Comparison of chromosome 3p deletions between cervical precancers synchronous with and without invasive cancer.
Authors: Guo Z. , Hu X. , Afink G. , Pontén F. , Wilander E. , Pontén J. .
Source: International Journal Of Cancer, 2000-05-15 00:00:00.0; 86(4), p. 518-23.
PMID: 10797265
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HPV typing and HPV16 E6-sequence variations in synchronous lesions of cervical squamous-cell carcinoma from Swedish patients.
Authors: Hu X. , Guo Z. , Tianyun P. , Pontén F. , Wilander E. , Andersson S. , Pontén J. .
Source: International Journal Of Cancer, 1999-09-24 00:00:00.0; 83(1), p. 34-7.
PMID: 10449604
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Detection and quantitation of human papillomavirus by using the fluorescent 5' exonuclease assay.
Authors: Josefsson A. , Livak K. , Gyllensten U. .
Source: Journal Of Clinical Microbiology, 1999 Mar; 37(3), p. 490-6.
PMID: 9986801
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