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.

Public Health Relevance

We expect our research to continue to contribute to our understanding of important mucosal immune responses to HPV, to give insight into potential therapies for HPV persistence, to gain insight into policies for screening and treatment and potential biomarkers in the triage of adolescents and young women with abnormal cytology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA051323-24
Application #
8504944
Study Section
Special Emphasis Panel (NSS)
Program Officer
Starks, Vaurice
Project Start
1990-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
24
Fiscal Year
2013
Total Cost
$1,399,693
Indirect Cost
$480,869
Name
University of California San Francisco
Department
Pediatrics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Scott, Mark E; Ma, Yifei; Farhat, Sepideh et al. (2015) Expression of nucleic acid-sensing Toll-like receptors predicts HPV16 clearance associated with an E6-directed cell-mediated response. Int J Cancer 136:2402-8
Hwang, Loris Y; Ma, Yifei; Moscicki, Anna-Barbara (2014) Biological and behavioral risks for incident Chlamydia trachomatis infection in a prospective cohort. Obstet Gynecol 124:954-60
Moscicki, Anna-Barbara; Puga, Ana; Farhat, Sepideh et al. (2014) Human papillomavirus infections in nonsexually active perinatally HIV infected children. AIDS Patient Care STDS 28:66-70
Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh et al. (2014) Natural history of anal human papillomavirus infection in heterosexual women and risks associated with persistence. Clin Infect Dis 58:804-11
Widdice, Lea; Ma, Yifei; Jonte, Janet et al. (2013) Concordance and transmission of human papillomavirus within heterosexual couples observed over short intervals. J Infect Dis 207:1286-94
Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh et al. (2013) Redetection of cervical human papillomavirus type 16 (HPV16) in women with a history of HPV16. J Infect Dis 208:403-12
Bosch, F Xavier; Broker, Thomas R; Forman, David et al. (2013) Comprehensive control of human papillomavirus infections and related diseases. Vaccine 31 Suppl 8:I1-31
Scott, Mark E; Shvetsov, Yurii B; Thompson, Pamela J et al. (2013) Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study. Int J Cancer 133:1187-96
Moscicki, Anna-Barbara; Kaul, Rupert; Ma, Yifei et al. (2012) Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% StarPharma LTD 7013 gel (VivaGel) to assess expanded safety. J Acquir Immune Defic Syndr 59:134-40
Hwang, Loris Y; Scott, Mark E; Ma, Yifei et al. (2011) Higher levels of cervicovaginal inflammatory and regulatory cytokines and chemokines in healthy young women with immature cervical epithelium. J Reprod Immunol 88:66-71

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