Human Papillomavirus

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Human Papillomavirus

• Infectious Agents
• Cancer

Diane M. Harper, MD, MPH, MS Director,
Gynecologic Cancer Prevention Research
Group Norris Cotton Cancer Center Dartmouth
Medical School
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HPV different from STDs

• HPV is common to ALL humanity
• Every person has at least one HPV infection
• 70-80 have had an anogenital infection at some
  time in their lives
• All ages are susceptible to infection
• HPV transmission must be skin to skin contact
• Any rubbing, touching, chafing, wrestling
  provides skin to skin contact
• Penetrative intercourse is only one method of
  skin to skin contact
• HPV type concordance between monogamous partners
  is only 20-30
• Due to low viral copy
• Due to inadequate sampling of partners genital
  skin
• Due to transmission patterns that are independent
  of intercourse
• HPV can only live in the cells of the skin that
  cover the whole body
• All STDs added together occur in 5 of the
  entire population (CDC)
• STDs are infections that reside inside the body
  organs
• STDs are transmitted by bodily fluids
• HIV in the blood
• HSV in the spinal column

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NORMAL SKIN
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HPV Transmission
SKIN - TO - SKIN
CONTACT
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Three Forms of HPV Infection

• Residential
• Usually minimally six weeks from exposure
• Can persist undetected for decades
• Can be LR or HR type
• Can be prevented with vaccination
• Episomal
• Virally active HPV located in the cell nucleus
• Separate from the human DNA
• Can be LR or HR type
• Can cause abnormal Pap tests
• Can be seen colposcopically
• Can be prevented with vaccination
• Integrated
• HPV DNA circle has opened and joined the human
  DNA
• Only HR types
• Causes abnormal Pap tests
• Seen colposcopically must be treated to prevent
  cancer
• Can be prevented with vaccination

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Residential
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Episomal
Releasing infectious particles
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Episomal
Multiple HPV virions per cell nucleus Not
integrated with human DNA
Histology of a low-grade lesion
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Integration
CIN 3
HPV DNA is circular HPV DNA opens HPV DNA inserts
into the human DNA
HPV DNA integrated in genome
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Episomal vs. Integration
Episomal HPV 16
Integrated HPV 16
Releasing infectious particles into the cervical
and vaginal secretions
8 week L1 L2 capsid proteins made indicating
virion assembly at this level of cellular
differentiation
Viral DNA replication continues rapidly
6 Week Early gene expression E6/E7
4 Week Early gene expression E4/E5
HPV
Basal Stem Cell
HPV Infection
CIN 2/3
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Invasive Cervical Cancer
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Randomized Controlled Trials Phase II - HPV
Vaccines
1Villa LL, et al. Lancet Oncol.
20056271-278. 2Harper DM, et al. Lancet.
20043641757-1765.
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1Villa LL, et al. Lancet Oncol.
20056271-278. 2Harper DM, et al. Lancet.
20043641757-1765.
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1Villa LL, et al. Lancet Oncol.
20056271-278. 2Harper DM, et al. Lancet.
20043641757-1765.
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1 Villa et al. Lancet Oncol. 20056271-278. 2
Harper et al. Lancet. 20043641757-1765.
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Efficacy of HPV Vaccines forHPV 16 or 18 () CIN
2,3
Phase III Trial
Skjeldestad FE, et al. IDSA. San Francisco, 2005.
Abstract LB-8a.
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1 Villa et al. Lancet Oncol. 20056271-278. 2
Harper et al. Lancet. 20043641757-1765.
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Conclusions

• HPV VLP vaccines are well tolerated
• Vaccines are highly immunogenic
• Vaccines induce high antibody titers
• Vaccines are highly effective in reducing
• Persistent HPV infection
• HPV-associated clinical disease