Judith Salmon Kaur, M'D'

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Judith Salmon Kaur, M.D.

• HPV VACCINES A NEW ERA OF HOPE FOR CANCER
  PREVENTION

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HPV Common Infection
Infected with HPV
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Infection Is Sexually Transmitted
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HPV types differ in disease association
Cutaneous
Mucosal
(40 types)
(60 types)
common
high-risk
low-risk
warts
types (16,18, and others)
types (6,11, others)
(hands/feet)

• low grade cervical abnormalities
• cervical cancer precursors intraepithelial
  neoplasia (CIN 2/3)
  adenocarcinoma in situ (AIS)
• anogenital cancer
• oropharyngeal/tonsillar cancers

• low grade cervical abnormalities
• genital warts
• respiratory papillomatosis

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Natural History of HPV Infection and Cervical
Cancer
Decades
1 year
Up to 5 years
Persistent infection
CIN 2/3 AIS
Initial HPV infection
Cancer
CIN 1
CLEARED HPV INFECTION

• cervical intraepithelial neoplasia
• adenocarcinoma in situ

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HPV Clearance

• Approximately 70 of new infections clear within
  one year, 91 within 2 years
• Most clearance in first 6 months
• Infection detected at more than one visit
  (usually 4-6 months apart)
• Most important predictor of high grade cervical
  cancer precursors

HPV Persistence
Ho et al., NEJM 1998 Moscicki et al., J Pediatr
1998 Franco et al., JID 1999
Molano et al., Am J Epidemiol 2003
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The Most Common Cancers in Women
Less developed countries
More developed countries



Breast
Cervix
Ovary
Endometrium
Colon/rectum
Lung
Stomach
600
200
400
600
0
400
200
Annual number of cases (thousands)
Adapted from Parkin et al, Eur J Cancer 37S4,
2001
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Estimates of the Number of Cases and Incidence
of Cervical Cancer, 2002
Cases/100,000
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HPV 16, 18, 31, and 45 Cause Most Cervical Cancer
Worldwide
Bosch et al., JNCI 1993
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Cervical Cancer Surveillance
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Age-Adjusted Invasive Cancer Incidence Rates,
Among Women, U. S., 2000
United States Cancer Statistics 2000 Incidence
NPCR
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NCI - 2005
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Cancers Attributable to Infection with Oncogenic
HPV Types, U.S., 2002
2002 US Cancer Statistics, CDC/NCI, 2005 Parkin
M. International Papillomavirus Conference,
Vancouver, Canada, 2005/Trotter H, Franco E,
Vaccine 2006 in press
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Vaccines are one of the best public health tools

• Ten Great Public Health Achievements United
  States, 19001999
• Vaccination
• Motor-vehicle safety
• Safer workplaces
• Control of infectious diseases
• Decline in deaths from coronary heart disease and
  stroke
• Safer and healthier foods
• Healthier mothers and babies
• Family planning
• Fluoridation of drinking water
• Recognition of tobacco use as a health hazard

• No communicable disease eradicated without
  vaccine
• Dramatic declines in morbidity mortality over
  last century (Frazer, et al. Pediatr Inf Dis J
  2006 25S65-81)
• Immunization among most cost-effective clinical
  preventive services (cost-saving or cost-neutral)
  (Coffield, et al. Am Prev Med 2001211-9)
• HPV vaccine brings us to new frontier
• 2nd STD vaccine
• 2nd cancer vaccine

Source MMWR 19994812
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The HPV Vaccine

• HPV L1 major capsid protein of the virus is
  antigen used for immunization
• Expression of L1 protein uses recombinant
  technology
• L1 proteins self-assemble into virus-like
  particles (VLP)

HPV VLP
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HPV Vaccine Dosage Schedule
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US Vaccine Adverse Event Reporting System (VAERS)

• Presented Feb, 2007 _at_ ACIP meeting
• 542 reports, 99 females
• 5 Most frequently reported symptoms

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Vaccine Safety Update

• No increased number of serious adverse events
• Most events have been local injection site
  reactions There were some cases of fainting
  after vaccination
• 4 cases of Guillain-Barre Syndrome (GBS)  Some of
  these persons also received other vaccines at the
  same time as Gardasil, most common, Menactra
• 3 deaths reported, 2 involving a pulmonary
  embolism and 1 involving myocarditis

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Healthcare Utilization Issues for Vaccine Delivery

• Few preventive visits made by adolescents
• Visits decline after 17 years of age
• Multiple providers
• Pediatricians more commonly seen by younger
  adolescents
• Implementation of HPV vaccine will be challenging
  since adolescent females will need to make more
  than one or two visits

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Cervical Cancer Screening Among Vaccinated
Population

• Cervical cancer screening no change planned
• 30 of cervical cancers caused by HPV types not
  in the quadrivalent HPV vaccine
• Vaccinated females could subsequently be infected
  with non-vaccine HPV types
• Sexually active females could have been infected
  prior to vaccination
• Decision to vaccinate should not be based on Pap
  testing, HPV DNA testing or HPV serologic testing
• Providers should educate girls and women about
  the importance of cervical cancer screening
  regardless of vaccine status

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DCPC Statement on Use of HPV Vaccines

• In support of the FDA, NCIRD, and the ACIP
• Regular cervical cancer screening is recommended
  for all women within 3 years of sexual debut or
  at age 21, whichever comes first.
• HPV vaccination for girls and women aged 9-26 is
  supported.
• HPV vaccination for women aged 27 or older is not
  supported.
• All women receiving the HPV vaccine should
  continue to receive the Pap test according to
  established screening recommendations.
• HPV vaccination is not a substitute for routine
  cervical cancer screening, and is not intended to
  treat cervical cancers.

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HPV Vaccine Era Priorities

• Vaccinate young women prior to sexual debut to
  maximize the benefit of the vaccine and achieve
  the highest level of immunogenicity.
• Create messages and policies that encourage
  continued cervical cancer screening.
• Conduct surveillance for precursor disease among
  those women vaccinated
• Encourage and provide regular cervical cancer
  screening for all women regardless of whether or
  not they receive the HPV vaccine series

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Integration of HPV Vaccination and Screening
Vaccinate Early Screen Late
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MARLEY JADE 1 YR OLD