Cervical Cancer: Molecular Impact of an Infectious Disease

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Cervical Cancer Molecular Impact of an
Infectious Disease
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HPV-16 E6 and E7 genes interact with cell cycle
machinery
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Background

• Worldwide, cervical cancer is the 2nd leading
  cause of cancer death in women
• Most cervical cancer is either squamous cell
  (85) or adenocarcinoma (12)
• Risk factors for squamous cell cancer
• Early coitarche
• Greater than 6-8 partners
• Cigarette smoking
• Oral contraceptives

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• During the sexual lifespan of a woman,
  approximately 70 will have been exposed to HPV
• The vast majority of HPV infections will regress
• Primary prevention is not utilized
• Stigma
• High prevalence
• Easy transmission

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• Cervical cancer is most strongly associated with
  sexually transmitted HPV infection
• HPV is endemic among sexually active humans
• HPV subtypes are classified into high and low
  risk groups

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Progressive infection of Washington State
University females with Human Papilloma Virus
over time
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Progressive infection over time with HPV in
college age population measured from time of
first intercourse
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HPV sub-types in genital infection in female WSU
cohort
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• Current management of cervical cancer is based on
  detection of disease-secondary prevention
• Papanicolaou technique for detection is flawed
• Acquisition error
• Preparation error
• Interpretation error
• Patient error
• Reporting error

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• Common reasons for presentation
• Abnormal vaginal bleeding, esp following
  intercourse (57)
• Abnormal pap smear (28)
• Low abdominal pain (9)
• Vaginal discharge (4)

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Normal transitioning to dysplastic epithelium in
cervix, With accompanying inflammation due to
poor barrier function
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Squamous dysplasia
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Future

• Topicals
• Retinoids
• Difluormethylornithine
• Development of prophylactic and therapeutic
  vaccines
• VLP (L1/L2)
• E6/E7