HPV

HPV

1. 8k bp circular DNA

   • ORFs
     • Early onset genes
       • E1
         • replicates viral episomes
       • E2
         • replication + transcription
         • regulates E6/E7
       • E4
         • Viral maturation + release
       • E5
         • host cell proliferation
         • inhibits immune response?
       • E6
         • p53 inactivation
           • uncontrolled cell cycle
       • E7
         • pRB inactivation
           • uncontrolled cell cycle
           • E7+pRB => E2F
             • p16INK4
               • ICC biomarker
     • Late onset genes
       • L1
         • major capsid protein
       • L2
         • minor capsid protein

2. HPV types

   • high risk
     • HPV 16
       • dominates 57% total
     • HPV 18
       • 16% SCC
       • dominates AdCA
   • low risk
     • HPV 6 & 11
   • host cell DNA integration
     • persistent HPV infection
       • mutations
     • host cell DNA polymerase

3. HPV vaccine

   • Gardasil & Cervarix
   • cross immunity
   • virus like particles
     • type specific
   • L1 origin

4. CIN

   • CIN1
     • 1/3 N/C
     • superficial/intermediate
   • CIN2
     • 2/3 N/C
     • intermediate/parabasal
       • medium clustering
   • CIN3
     • 2/3+ N/C
     • parabasal/basal
       • grapes
       • clustering