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Grant Details

Grant Number: 5R37CA051323-24 Interpret this number
Primary Investigator: Moscicki, Anna-Barbara
Organization: University Of California, San Francisco
Project Title: Natural History of HPV Infection to Neoplasia
Fiscal Year: 2013
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Abstract

The study's ultimate design is to chronicle the natural history of HPV in adolescents and young women in a prospective cohort which was established in 1990. The study funded in 2005 was designed to examine the innate and adaptive mucosal immune responses to HPV in the context of HPV acquisition, clearance, and persistence. Over the last 18 years, we have recruited over 1400 women into the cohort, which in total reflect over 20,000 visits and a repository with well over 100,000 stored samples. In the last 4 years have 27 publications with 7 manuscripts submitted over the last 4 months. We now have the opportunity in the next few years to continue monitoring this inimitable cohort as well as begin to mine the valuable repository. We have collected and continue to collect a rich repository of blood, saliva, cervical cells and mucous, vulvar and anal samples. One of our goals over the new few years is to establish more elaborate repository databases. The logging and monitoring of 100,000 samples with continued repository is an immense challenge. One of our aims is to continue studying the mucosal immune response in more depth. We believe this will be critical in discovering novel therapeutic approaches to HPV induced disease since HPV is largely a localized infection. We plan to continue our investigations into innate responses including Toll-like receptors, with a focus on defining the downstream expression of regulatory cytokines. This will include the development of assays to include the important IFN-alpha family thought to be an important cytokine expressed after TLR activation. We also plan to investigator the role of TLRs and regulatory T cells in more depth with studies using flow cytometry. In studying the immune response, we have also focused on the development of the cervix in young women. We continue to examine the role of epithelial topography in women's vulnerabilities to HPV and cancer. We plan to work with bioengineers in development of more sophisticated techniques to measure the process of squamous metaplasia, the cells thought vulnerable to cancer change. Another goal is to capture mucosal immune response in adolescents vaccinated with the HPV vaccine. We plan to recruit an additional 100 sexually active adolescents recently vaccinated with the HPV vaccine to our study of mucosal immune responses. This will allow us to examine mechanisms of protection associated with the prophylactic vaccine. This grant will allow the valuable work of our staff to continue the retention of the cohort as well recruitment of the vaccinated adolescents and to collect the valuable samples. Expansion of immune studies, data analysis and data management will remain centerpieces over the coming years.

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Publications

Comprehensive control of human papillomavirus infections and related diseases.
Authors: Bosch FX, Broker TR, Forman D, Moscicki AB, Gillison ML, Doorbar J, Stern PL, Stanley M, Arbyn M, Poljak M, Cuzick J, Castle PE, Schiller JT, Markowitz LE, Fisher WA, Canfell K, Denny LA, Franco EL, Steben M, Kane MA, Schiffman M, Meijer CJ, Sankaranarayanan R, Castellsagué X, Kim JJ, Brotons M, Alemany L, Albero G, Diaz M, de Sanjosé S, authors of ICO Monograph Comprehensive Control of HPV Infections and Related Diseases Vaccine Volume 30, Supplement 5, 2012
Source: Vaccine, 2013 Dec 31;31 Suppl 7, p. H1-31.
PMID: 24332295
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Comprehensive control of human papillomavirus infections and related diseases.
Authors: Bosch FX, Broker TR, Forman D, Moscicki AB, Gillison ML, Doorbar J, Stern PL, Stanley M, Arbyn M, Poljak M, Cuzick J, Castle PE, Schiller JT, Markowitz LE, Fisher WA, Canfell K, Denny LA, Franco EL, Steben M, Kane MA, Schiffman M, Meijer CJ, Sankaranarayanan R, Castellsagué X, Kim JJ, Brotons M, Alemany L, Albero G, Diaz M, de Sanjosé S, ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012
Source: Vaccine, 2013 Dec 30;31 Suppl 6, p. G1-31.
PMID: 24331817
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Comprehensive control of human papillomavirus infections and related diseases.
Authors: Bosch FX, Broker TR, Forman D, Moscicki AB, Gillison ML, Doorbar J, Stern PL, Stanley M, Arbyn M, Poljak M, Cuzick J, Castle PE, Schiller JT, Markowitz LE, Fisher WA, Canfell K, Denny LA, Franco EL, Steben M, Kane MA, Schiffman M, Meijer CJ, Sankaranarayanan R, Castellsagué X, Kim JJ, Brotons M, Alemany L, Albero G, Diaz M, de Sanjosé S, authors of the ICO Monograph ?Comprehensive Control of HPV Infections and Related Diseases? Vaccine Volume 30, Supplement 5, 2012
Source: Vaccine, 2013 Dec 29;31 Suppl 5, p. F1-31.
PMID: 24331745
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Concordance and transmission of human papillomavirus within heterosexual couples observed over short intervals.
Authors: Widdice L, Ma Y, Jonte J, Farhat S, Breland D, Shiboski S, Moscicki AB
Source: J Infect Dis, 2013 Apr 15;207(8), p. 1286-94.
EPub date: 2013 Jan 14.
PMID: 23319742
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Updating the natural history of human papillomavirus and anogenital cancers.
Authors: Moscicki AB, Schiffman M, Burchell A, Albero G, Giuliano AR, Goodman MT, Kjaer SK, Palefsky J
Source: Vaccine, 2012 Nov 20;30 Suppl 5, p. F24-33.
PMID: 23199964
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Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% StarPharma LTD 7013 gel (VivaGel) to assess expanded safety.
Authors: Moscicki AB, Kaul R, Ma Y, Scott ME, Daud II, Bukusi EA, Shiboski S, Rebbapragada A, Huibner S, Cohen CR
Source: J Acquir Immune Defic Syndr, 2012 Feb 1;59(2), p. 134-40.
PMID: 22067666
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Human papillomavirus concordance in heterosexual couples.
Authors: Widdice LE, Breland DJ, Jonte J, Farhat S, Ma Y, Leonard AC, Moscicki AB
Source: J Adolesc Health, 2010 Aug;47(2), p. 151-9.
EPub date: 2010 Mar 24.
PMID: 20638007
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Misclassification of current status data.
Authors: McKeown K, Jewell NP
Source: Lifetime Data Anal, 2010 Apr;16(2), p. 215-30.
EPub date: 2010 Feb 16.
PMID: 20157848
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Comparison of natural histories of human papillomavirus detected by clinician- and self-sampling.
Authors: Moscicki AB, Widdice L, Ma Y, Farhat S, Miller-Benningfield S, Jonte J, Jay J, de Medina CG, Hanson E, Clayton L, Shiboski S
Source: Int J Cancer, 2010 Oct 15;127(8), p. 1882-92.
PMID: 20104517
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Diminished IFN-gamma and IL-10 and elevated Foxp3 mRNA expression in the cervix are associated with CIN 2 or 3.
Authors: Scott ME, Ma Y, Kuzmich L, Moscicki AB
Source: Int J Cancer, 2009 Mar 15;124(6), p. 1379-83.
PMID: 19089920
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Validation of reference genes in cervical cell samples from human papillomavirus-infected and -uninfected women for quantitative reverse transcription-PCR assays.
Authors: Daud II, Scott ME
Source: Clin Vaccine Immunol, 2008 Sep;15(9), p. 1369-73.
EPub date: 2008 Jul 16.
PMID: 18632922
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Determination of cytokine protein levels in cervical mucus samples from young women by a multiplex immunoassay method and assessment of correlates.
Authors: Lieberman JA, Moscicki AB, Sumerel JL, Ma Y, Scott ME
Source: Clin Vaccine Immunol, 2008 Jan;15(1), p. 49-54.
EPub date: 2007 Oct 31.
PMID: 17978011
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Covariates of cervical cytokine mRNA expression by real-time PCR in adolescents and young women: effects of Chlamydia trachomatis infection, hormonal contraception, and smoking.
Authors: Scott ME, Ma Y, Farhat S, Shiboski S, Moscicki AB
Source: J Clin Immunol, 2006 May;26(3), p. 222-32.
EPub date: 2006 May 16.
PMID: 16783462
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Patterns of CD8 T-cell epitopes within the human papillomavirus type 16 (HPV 16) E6 protein among young women whose HPV 16 infection has become undetectable.
Authors: Nakagawa M, Kim KH, Moscicki AB
Source: Clin Diagn Lab Immunol, 2005 Aug;12(8), p. 1003-5.
PMID: 16085919
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Different methods of identifying new antigenic epitopes of human papillomavirus type 16 E6 and E7 proteins.
Authors: Nakagawa M, Kim KH, Moscicki AB
Source: Clin Diagn Lab Immunol, 2004 Sep;11(5), p. 889-96.
PMID: 15358648
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Utility of cervicography in HIV-infected and uninfected adolescents.
Authors: Moscicki AB, Durako SJ, Ma Y, Darragh T, Vermund SH
Source: J Adolesc Health, 2003 Mar;32(3), p. 204-13.
PMID: 12606114
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Time course of humoral and cell-mediated immune responses to human papillomavirus type 16 in infected women.
Authors: Nakagawa M, Viscidi R, Deshmukh I, Costa MD, Palefsky JM, Farhat S, Moscicki AB
Source: Clin Diagn Lab Immunol, 2002 Jul;9(4), p. 877-82.
PMID: 12093689
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Cell-mediated immune response to human papillomavirus infection.
Authors: Scott M, Nakagawa M, Moscicki AB
Source: Clin Diagn Lab Immunol, 2001 Mar;8(2), p. 209-20.
PMID: 11238198
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Persistence of human papillomavirus type 16 infection is associated with lack of cytotoxic T lymphocyte response to the E6 antigens.
Authors: Nakagawa M, Stites DP, Patel S, Farhat S, Scott M, Hills NK, Palefsky JM, Moscicki AB
Source: J Infect Dis, 2000 Aug;182(2), p. 595-8.
EPub date: 2000 Jul 28.
PMID: 10915094
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CD4-positive and CD8-positive cytotoxic T lymphocytes contribute to human papillomavirus type 16 E6 and E7 responses.
Authors: Nakagawa M, Stites DP, Palefsky JM, Kneass Z, Moscicki AB
Source: Clin Diagn Lab Immunol, 1999 Jul;6(4), p. 494-8.
PMID: 10391849
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The pediatrician and the sexually active adolescent. A primer for sexually transmitted diseases.
Authors: Lappa S, Moscicki AB
Source: Pediatr Clin North Am, 1997 Dec;44(6), p. 1405-45.
PMID: 9400580
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T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia.
Authors: Nakagawa M, Stites DP, Farhat S, Judd A, Moscicki AB, Canchola AJ, Hilton JF, Palefsky JM
Source: Clin Diagn Lab Immunol, 1996 Mar;3(2), p. 205-10.
PMID: 8991637
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Bcl-2 protooncogene expression in cervical carcinoma cell lines containing inactive p53.
Authors: Liang XH, Mungal S, Ayscue A, Meissner JD, Wodnicki P, Hockenbery D, Lockett S, Herman B
Source: J Cell Biochem, 1995 Mar;57(3), p. 509-21.
PMID: 7768985
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Detection of human papillomavirus type 16/18 DNA in cervicovaginal cells by fluorescence based in situ hybridization and automated image cytometry.
Authors: Siadat-Pajouh M, Periasamy A, Ayscue AH, Moscicki AB, Palefsky JM, Walton L, DeMars LR, Power JD, Herman B, Lockett SJ
Source: Cytometry, 1994 Mar 1;15(3), p. 245-57.
PMID: 8187584
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Co-localization of the tumor-suppressor protein p53 and human papillomavirus E6 protein in human cervical carcinoma cell lines.
Authors: Liang XH, Volkmann M, Klein R, Herman B, Lockett SJ
Source: Oncogene, 1993 Oct;8(10), p. 2645-52.
PMID: 8397367
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