Clinical trial NCT01366742: Natural History of HPV From Infection to Neoplasia in Adolescents and Young Women
Official title: Natural History of Human Papillomavirus From Infection to Neoplasia in Adolescents and Young Women - Effect of Tobacco on Cervical Neoplasia in Young Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Papillomavirus
CIN 2
CIN 3
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2011-06-06
Enrollment: 900
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Community

Brief summary: The natural history of human papillomavirus (HPV) is most likely influenced by both innate and adaptive mucosal immunity. More specifically, we hypothesize that Toll like receptors (TLR) play an important role in cervical innate immunity to HPV through secretions of proinflammatory, chemotactic and anti-viral cytokines. Up-regulated TLR expression will also result in activation of dendritic cells and T cells that in turn will promote a T helper (Th) l like response through secretion of several cytokines and consequently, the induction of a successful cell mediated immune (CMI) response.

Detailed description: The natural history of HPV is most likely influenced by both innate and adaptive mucosal immunity. More specifically, we hypothesize that Toll like receptors (TLRs) play an important role in cervical innate immunity to HPV through secretions of proinflammatory, chemotactic and anti-viral cytokines. Up-regulated TLR expression will also result in activation of dendritic cells and T cells that in turn will promote a Thl like response through secretion of several cytokines and consequently, the induction of a successful cell mediated immune (CMI) response.

We propose to: 1) examine, in cervical cell samples, the association among TRL expression, TRL-associated cytokines that mediate innate immunity and clearance of incident HPV infection; 2) examine, in cervical cell samples, the association among TRL expression, TRL-associated cytokines that induce and mediate adaptive immunity and HPV clearance; and 3) examine the association among TLR induced Th-1 responses measured in cervical cell samples, HPV specific CMI responses detected in peripheral blood (PB) and HPV clearance. Adolescent and young women who were a) entered into the cohort during the initial 1990-1995 period and have continued to be followed and b) entered into the cohort during the last recruitment wave (2000-2005) will be asked to continue followup for an additional five years (2005-2010). These women will have been well characterized at the time of the initiation of this study with HPV at their entry visit and 4-month interval sampling for HPV DNA, cytology, bacterial vaginosis, colpophotographs (assessment of cervical maturation), C. trachomatis and N. gonorrhea testing, cervical cell cytokines by reverse transcriptase polymerase chain reaction (RT-PCR) and peripheral blood (PB) CMI for HPV 16 positive women. Women will be continued to be characterized for the above at the same intervals through-out the follow-up. Measures of innate and adaptive immunity by RT PCR using cervical cells and by Luminex technology have been added to the same 4 month interval testing as HPV DNA, cytology and other cervical cytokines described. Women positive for HPV 16 will get additional blood for CMI using Interferon (IFN)-y Enzyme linked immunospot (EliSpot) technique for detection of anti-E6 and E7 responses. We also examine the natural history of anal HPV in these women. We acknowledge that this design simplifies the pleiotropic nature of cytokines. However, we feel that this model reflects plausible mechanisms involved in HPV control and is feasible to test in our cohort. Information garnered from this type of study will be critical in developing vaccine strategies and therapies as well as illuminating immune responses developed in the mucosal epithelium.

Eligibility criteria: Inclusion:

* Age 12 to 22 years
* Sexually active less than 6 years
* Received one dose of the HPV vaccine

Exclusion:

* Planning on moving in 3 years
* Prior history of treatment for CIN
* Immunocompromised (ie transplant patient, HIV)
* Pregnant

Primary outcomes:
measure: Cervical Intraepithelial neoplasia (CIN) 2/3
timeFrame: 1990 to current
Secondary outcomes:
measure: HPV persistence
timeFrame: 1990 to present
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: SFSU Student Health Center
state: California
city: San Leandro
country: United States
facility: HPV Study - San Leandro Office
state: California
Study officials:
affiliation: University of California, San Francisco
name: Anna-Barbara Moscicki, MD
role: PRINCIPAL_INVESTIGATOR
References: