What Do We Know About Cervical Cancer, HPV and HPV Vaccines

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What Do We Know About Cervical Cancer, HPV and
HPV Vaccines ?

• Ricky Lu
• Amy Kleine
• MAQ Mini-University
• 5 October 2007

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Global Incidence of Cervical Cancer
Incidence /100,000 women

• 470,000 New Cases
• 235,000 Deaths
• 80 in Developing Countries

Globocan 2002
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What and Where is the Cervix ?
Squamous epithelium lining
Transformation Zone
Cervical Opening
Columnar epithelium lining
Squamocolumnar Junction-SCJ
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What is Cervical Cancer?

• Starts in lining of cervix
• Gradual development from precancer
• Good prognosis with early diagnosis and
  treatment
• Stage 1 - 80-90
• Stage 2 50-65
• Treatment
• Surgery
• Radiotherapy
• Chemotherapy

• Squamous Cell Carcinoma (SCC)
• 80-90 of Cervical Cancer
• Squamous cells covering the cervix
• Starts at the Squamocolumnar junction
• Adenocarcinoma
• 10-20 of Cervical cancer
• Mucus producing cervical cells

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Human Papillomavirus (HPV)

• DNA VIRUS
• Preferentially infect squamous epithelial cells
• 100 genotypes
• 40 genital HPV types

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Genital HPV Types and Outcomes
Uncertain cancer potential HPV 26, 34, 53, 57,
66, 83
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Epidemiology of HPV

• The most common STI worldwide
• 80 sexually active adults in the US infected
  with at least one HPV type by age 501
• Peak prevalence during adolescence and young
  adulthood
• Prevalence decreases with age
• HPV 16 is the most common HR type (HPV 16/18
  account for 70 of cervical Cancer)
• Centers for Disease Control and Prevention.
  Rockville, Md CDC National Prevention
  Information Network 2004

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HPV Test
John Sellors, PATH, 2007
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Natural History of CIN and Cervical Cancer
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Link between HPV and HIV Infections

• Different natural history for HPV infection in
  HIV sero women- it is more
• Prevalent across age groups
• Persistent
• Likely to develop dysplasia
• High grade dysplasia/cancer stage
• Likely not to survive their cancer
• Persistence of HPV Infection in HIV Sero women
• HIV infection affects cell-mediated immunity
• 6-18 x likely to persist
• Lower CD4 cell counts is a risk factor for
  persistence (HPV DNA clearance unlikely in CD4
  cell count
• Inherent interaction between HPV and HIV
  infection?

Shaun Biggers, 2000Moscicki et al., 2000
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Cervical Cancer is Preventable
15
30
45
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Cervical Cancer Prevention Options

• Primary Prevention
• Behavioral Interventions
• Prophylactic Vaccines
• Quadrivalent or GARDASIL(HPV 6/11/16/18)
• Bivalent or CERVARIX (HPV 16/18)
• Vaccinated women will still be at risk for
  contracting other high-risk HPV types
• Secondary Prevention
• Screening
• Cytology based
• Unaided Visual Inspection
• Magnified Visual Inspection
• HPV Test

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HPV VACCINES CHARACTERISTICS
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HPV vaccines Key findings

• Vaccines efficacy extremely high against HPV
  vaccine-type disease in HPV naive women
• Vaccines are much less effective in non-naïve or
  women already exposed to HPV types 16/18,
• For the both vaccines, partial protection against
  new infections by two other types has been
  reported
• Types 31 and 45
• Good antibody persistence for 5 or more years
• Acceptable safety profile

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Considerations for Introducing HPV Vaccine

• Affordability
• Healthcare infrastructure
• Capacity to initiate and sustain vaccination
• Cost effectiveness
• Cultural Acceptability
• Political Will
• Public Support
• Capacity for secondary prevention-screening and
  treatment
• Agnosti and Goldie, 2007

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Key Research Questions

• How to motivate parents and teens for
  vaccination?
• Community-based or school-based delivery?
• What is the best age for community-based
  delivery?
• What is the best school-based delivery strategy?
• Alternate dose schedules?
• Two doses only?
• What lessons can be learned for eventual HIV
  vaccine introduction?

Scott Wittet, PATH 2006-2011 Cervical cancer
Vaccine project
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Is Secondary Prevention Still Needed As Vaccines
Become Available

• Vaccine may not be available in communities and
  countries most affected by cervical cancer (for a
  long while). Many competing health priorities
• Reaching pre-adolescents is problematic. School
  health programs are non existent and do not reach
  more the 60 of girls out of school anyway.
• Early age of sexual debut and some uncertainty on
  how long vaccine effectiveness will last.
• Vaccine is only highly effective if all doses
  completed. Long term follow up is currently a
  significant challenge for all public heath
  programs that require return visits.

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What women in the US and other developed
countries have had for 30 years since, women in
Africa, Latin America and Asia can have now
The right to protect themselves from cervical
cancer ! 
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The Single Visit Approach (SVA) to Cervical
Cancer Prevention using Visual Inspection with
Acetic Acid (VIA) and cryotherapy
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Limitations of Pap Smear

• Complex laboratory test
• (sampling instruments, slides, fixatives,
  reagents, cover slips, processing equipment,
  microscopes,)
• Requires trained cytotechnician for reading and
  pathologist for review
• Continuous monitoring needed to maintain
  high-quality results
• Reports often take 1 week to 3 months to obtain
• Follow-up of women is difficult
• Usually available only in large cities in many
  countries

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What Is VIA?

• Looking at the cervix to detect abnormalities
  after applying dilute (3-5) acetic acid
  (vinegar).
• Acetic acid enhances and marks a precancerous
  lesion or cancer by turning it a whitish hue
  (acetowhite change).

White Lesion
Normal (No White lesion)
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Why VIA is a Practical Alternative to Pap Smears

• Safe, easy to perform and inexpensive
• Can be learned by all types of healthcare
  professionals
• All equipment and supplies are available locally
• Results are available immediately
• Potential for immediate link to outpatient
  treatment
• Suitable for lowest-resource settings

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VIA Test Qualities
Test qualities are similar to Pap Smear
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SAFE Demonstration Projects Conclusions

• The Single-Visit Approach using VIA and
  Cryotherapy is
• Safe for testing and treating women at district
  hospitals and in primary health care facilities,
• Acceptable to both patients and providers,
• Feasibleas well as cost effectivefor use in
  low-resource settings.
• Based on results of SAFE Demonstration Projects
  conducted between 2000 and 2002.
• Thailand 6000 women tested, 13 VIA-positive
• Ghana Urban 4089 women tested, 12 VIA-positive
• Ghana Rural 1437 women tested, 8 VIA-positive

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Long-Term Impact of VIA screening

• Effect of visual screening on cervical cancer
  incidence and mortality in Tamil Nadu, India a
  cluster-randomised trial (Lancet 2007
  370398-406)
• Published by group from International Agency for
  Research on Cancer (IARC)
• KEY FINDINGS
• Cervical cancer burden was reduced by a single
  round of VIA screening. 25 reduction in
  incidence and 35 reduction in mortality.
• All-cause mortality was significantly reduced in
  the intervention group compared to the controls.
• VIA screening, in the presence of good training
  and sustained quality assurance, is an effective
  method to prevent cervical cancer in developing
  countries.

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Elements of Successful Screening Program
Source Max Parkin, IARC
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Outpatient Treatment Options
Low
1500 1 Loop electrosurgical excision procedure.
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Single Visit Approach Steps

• 1 Counseling
• 2 Speculum Exam to see Cervix
• 3 Apply 3-5 Acetic Acid to Cervix
• 4 Inspect Cervix for lesions
• 5 Discuss results with the woman. Offer
  treatment option if positive

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Single Visit Approach Steps

• 6 Speculum exam to re-view cervix
• 7 Apply Cryoprobe and freeze for 3 minutes
• 8 Defrost for 5 minutes
• 9 Re-freeze for 3 minutes
• 10 Post treatment and followup instructions

Cryotherapy Before and After
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CECAP Country Programs

• Thailand
• Ghana
• Malawi
• Philippines
• Indonesia
• South Africa

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Malawi Experience
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Thailand Experience
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Take Home Messages

• Cervical cancer is a burden for women in
  developing countries
• Cervical cancer deaths are highly preventable
• Persistent, chronic HPV infection leads to
  cervical cancer
• HIV infection increases the risk of Cervical
  Cancer
• HPV vaccine is highly effective in naïve females
  for High Risk HPV types 16/18
• Screening services will continue to be needed
  even for vaccinated women
• Every woman needs to be screened at least 1x in
  her lifetime