Natural History of HPV From Infection to Neoplasia in Adolescents and Young Women
Condition: Human Papillomavirus; CIN 2; CIN 3
MeSH terms: Neoplasms
Study type: Observational

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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Community
      
Biospecimen description: 
      Rbc, WBC vaginal lavages ,cytology,saliva ,anal samples