Grant Number:	1R01CA087905-01A1 Interpret this number
Primary Investigator:	Moscicki, Anna-Barbara
Organization:	Univ Of California At San Francisco
Project Title:	Natural History of Cin2 in Adolescents
Fiscal Year:	2001

This is a 5 year prospective study designed to: 1) examine the natural history of CIN-2 (cervical intra-epithelial lesions) subset of high grade squamous intra-epithelial lesions (HSIL) among adolescents, and 2) identify immunologic and behavioral factors associated with regression of CIN 2 lesions. The study of immunologic and behavioral factors that may influence CIN 2 regression will include: sustained local (cervical) Th-1 like cytokine response, systemic cytotoxic T lymphocyte (CTL) responses to HPV (for HPV 16 positive women only), size of lesion at diagnosis, amount of cervical immaturity (ectopy) at diagnosis, and hormonal contraception. Other factors that will be monitored for possible effects include high risk sexual behavior and outcomes (multiple partners, substance use, pregnancy, sexually transmitted infections, and bacterial vaginosis). Last, this study proposes to compare local immunologic responses among women who at baseline visit are diagnosed with CIN-1, CIN-2 and normal histology on biopsy. Approximately 40,000 young women 19 years or younger are expected to undergo cervical cytology screening within the Northern California Kaiser Permanente clinics over a 24 month period. Adolescents aged 13-19 years with abnormal cytology (estimated N=2680) will be recruited. Baseline examination will include interview and cervical samples for HPV DNA testing and quantitative cytokine studies using reverse transcriptase polymerase chain reaction techniques. Colpophotographs will be obtained to determine lesion size. All samples will be obtained prior to biopsy. Those with biopsy-confirmed CIN 2 (N=416) will be followed every 3 months using interview, colposcopy, HPV DNA testing, and cytology and undergo immune studies (cervical cell cytokine analysis using real-time RT-PCR and peripheral blood CTL assays on women with HPV 16 infection) until the end of the study. Women with CIN-3 are exited for standard therapy. Those with biopsied confirmed low grade (L) SIL or less will exited. Understanding of the natural history of CIN 2 will be critical in efforts to construct cost-effective strategies for cancer screening in adolescents. In addition, defining immunologic factors associated with CIN 2 regression will have important implications for vaccine and therapeutic strategies and defining clinical (including repeated HPV DNA testing) and behavioral risks will have important implications for triage and counseling strategies.




The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions.
Authors: Mitra A. , MacIntyre D.A. , Ntritsos G. , Smith A. , Tsilidis K.K. , Marchesi J.R. , Bennett P.R. , Moscicki A.B. , Kyrgiou M. .
Source: Nature Communications, 2020-04-24 00:00:00.0; 11(1), p. 1999.
EPub date: 2020-04-24 00:00:00.0.
PMID: 32332850
Related Citations

Toll-like receptors: Important immune checkpoints in the regression of cervical intra-epithelial neoplasia 2.
Authors: Halec G. , Scott M.E. , Farhat S. , Darragh T.M. , Moscicki A.B. .
Source: International Journal Of Cancer, 2018-08-19 00:00:00.0; , .
EPub date: 2018-08-19 00:00:00.0.
PMID: 30121951
Related Citations

HPV-associated cancers: it's not all about the cervix.
Authors: Moscicki A.B. .
Source: Preventive Medicine, 2011 Oct; 53 Suppl 1, p. S3-4.
PMID: 21962469
Related Citations

Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women.
Authors: Moscicki A.B. , Ma Y. , Wibbelsman C. , Darragh T.M. , Powers A. , Farhat S. , Shiboski S. .
Source: Obstetrics And Gynecology, 2010 Dec; 116(6), p. 1373-80.
PMID: 21099605
Related Citations

Diminished IFN-gamma and IL-10 and elevated Foxp3 mRNA expression in the cervix are associated with CIN 2 or 3.
Authors: Scott M.E. , Ma Y. , Kuzmich L. , Moscicki A.B. .
Source: International Journal Of Cancer, 2009-03-15 00:00:00.0; 124(6), p. 1379-83.
PMID: 19089920
Related Citations

Risks for cervical intraepithelial neoplasia 3 among adolescents and young women with abnormal cytology.
Authors: Moscicki A.B. , Ma Y. , Wibbelsman C. , Powers A. , Darragh T.M. , Farhat S. , Shaber R. , Shiboski S. .
Source: Obstetrics And Gynecology, 2008 Dec; 112(6), p. 1335-42.
PMID: 19037044
Related Citations

Management of adolescents who have abnormal cytology and histology.
Authors: Moscicki A.B. .
Source: Obstetrics And Gynecology Clinics Of North America, 2008 Dec; 35(4), p. 633-43; x.
PMID: 19061822
Related Citations

Issues in human papillomavirus vaccination in adolescents.
Authors: Moscicki A.B. , Smith J.S. .
Source: The Journal Of Adolescent Health : Official Publication Of The Society For Adolescent Medicine, 2008 Oct; 43(4 Suppl), p. S1-4.
PMID: 18809142
Related Citations

HPV Vaccines: today and in the Future.
Authors: Moscicki A.B. .
Source: The Journal Of Adolescent Health : Official Publication Of The Society For Adolescent Medicine, 2008 Oct; 43(4 Suppl), p. S26-40.
PMID: 18809143
Related Citations

Validation of reference genes in cervical cell samples from human papillomavirus-infected and -uninfected women for quantitative reverse transcription-PCR assays.
Authors: Daud I.I. , Scott M.E. .
Source: Clinical And Vaccine Immunology : Cvi, 2008 Sep; 15(9), p. 1369-73.
PMID: 18632922
Related Citations

Determination of cytokine protein levels in cervical mucus samples from young women by a multiplex immunoassay method and assessment of correlates.
Authors: Lieberman J.A. , Moscicki A.B. , Sumerel J.L. , Ma Y. , Scott M.E. .
Source: Clinical And Vaccine Immunology : Cvi, 2008 Jan; 15(1), p. 49-54.
PMID: 17978011
Related Citations

Conservative management of adolescents with abnormal cytology and histology.
Authors: Moscicki A.B. .
Source: Journal Of The National Comprehensive Cancer Network : Jnccn, 2008 Jan; 6(1), p. 101-6.
PMID: 18267063
Related Citations

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 M.E. , Ma Y. , Farhat S. , Shiboski S. , Moscicki A.B. .
Source: Journal Of Clinical Immunology, 2006 May; 26(3), p. 222-32.
PMID: 16783462
Related Citations

Cervical cytology testing in teens.
Authors: Moscicki A.B. .
Source: Current Opinion In Obstetrics & Gynecology, 2005 Oct; 17(5), p. 471-5.
PMID: 16141760
Related Citations

Human papilloma virus, papanicolaou smears, and the college female.
Authors: Moscicki A.B. .
Source: Pediatric Clinics Of North America, 2005 Feb; 52(1), p. 163-77, ix.
PMID: 15748929
Related Citations