|Grant Number:||3R01CA087905-05S1 Interpret this number|
|Primary Investigator:||Moscicki, Anna-Barbara|
|Organization:||University Of California, San Francisco|
|Project Title:||Natural History of Cin2 in Adolescents|
With the introduction of the HPV vaccine, policies toward screening practices will need to be reevaluated with a goal of achieving a reasonable balance between maximizing benefits, minimizing risks, and achieving cost-effectiveness. Although current practice is to treat CIN 2 the same as CIN 3, many question this practice in young women since these young women remain a vulnerable population to treatment side effects that are related to fertility. In addition, understanding mechanisms that are related to CIN 2 regression are important in developing treatment strategies. In a prospective study of adolescents and young women aged 13 to 24 years of age, our first aims are to:1a) define the rates of CIN 2 regression and examine the role of hormonal contraceptives, estrogen and progesterone receptor expression, and mucosal mRNA markers of cellmediated immunity (CMI) in regression of CIN-2 lesions. The second aim is to conduct a cost-effectiveness analysis of alternative strategies for adolescents and young women with CIN 2 in the US. This will conducted by 2a) Modifying a natural history model of cervical neoplasia in adolescents to explicitly include health states that reflect CIN 2 and CIN 3 separately, and calibrate the model to the U.S. population; 2b) Integrating the best available data, including the primary data collected in this study, to develop input model parameters with special attention to age-specific probabilities in adolescents and young girls; 2c) To use the refined model to estimate the short and long-term benefits, harms, and costs of alternative screening strategies for adolescents and young women with CIN 2. Women who were recruited into the Kaiser Permanente Medical Group of Northern California (KPMG-NC) study of CIN 2 (n=76) will be asked to continue follow-up. In addition, 25 young women aged 13-24 years of age diagnosed with CIN 2 by histology at 7 participating KPMG-NC Clinics will be asked to participate. The study proposes to observe young women with a biopsy verified CIN-2 lesion at 4 month intervals with HPV testing, cytology and colposcopy, b) examine risk factors using interview and chart review and c) examine estrogen and progesterone receptor expression and local immune responses (IFN-y, IL-12, IL-10 and T-reg) by sampling of cervical tissue. The data we obtain on the natural history of CIN 2 will be formally incorporated into a computer-based microsimulation model of cervical neoplasia and cancer. This study will be paramount in the development of proper guidelines for screening and triage of abnormal cytology and will give insight into immunologic and hormonal mechanisms associated with CIN-2 development. Relevance: The data gathered from this study will be used develop formal costeffectiveness analysis of alternative screening strategies for cervical neoplasia and cancer in adolescents in the U.S. and specifically assess how best to modify cytology-based screening, utilize HPV diagnostics, and tailor aoDrooriate follow-uo strategies for adolescents and vouna women diaanosed with CIN 2
Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women.
Authors: Moscicki AB, Ma Y, Wibbelsman C, Darragh TM, Powers A, Farhat S, Shiboski S
Source: Obstet Gynecol, 2010 Dec;116(6), p. 1373-80.
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.
Risks for cervical intraepithelial neoplasia 3 among adolescents and young women with abnormal cytology.
Authors: Moscicki AB, Ma Y, Wibbelsman C, Powers A, Darragh TM, Farhat S, Shaber R, Shiboski S
Source: Obstet Gynecol, 2008 Dec;112(6), p. 1335-42.
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.
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.
Human papilloma virus, papanicolaou smears, and the college female.
Authors: Moscicki AB
Source: Pediatr Clin North Am, 2005 Feb;52(1), p. 163-77, ix.