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ARCHIVED - Literature review on HPV 6, 11, 16 and 18: Disease and Vaccine Characteristics

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M Dawar1, S Dobson2, S Deeks3

June 2007

1 Field Epidemiologist, Canadian Field Epidemiology Program, Public Health Agency of Canada
2 Clinical Associate Professor, Vaccine Evaluation Centre, University of British Columbia
3 Senior Medical Specialist, Immunization and Respiratory Infections Division, Centre for Infectious Disease Prevention and Control, Public Health Agency of Canada

(full PDF version 366 KB)

This review was commissioned by the Public Health Agency of Canada (PHAC).

Table of Contents

  1. Acronyms & Glossary
  2. Introduction
  3. Methods
  4. Results
    • IV.1 Burden of disease caused by HPV 6, 11, 16 and 18
      Table 1: HPV positivity (all genotypes, 16 and 18) for selected cancers and precancerous lesions worldwide
      Table 2: Other risk factors associated with cervical cancer
    • IV.2 HPV Vaccines, Gardasil™ and Cervarix™
      1. Nature and characteristics of immunizing agent
      2. Characteristics of the commercial products and administration schedule
      3. Vaccine manufacturers, production capacity and supply to Canada
      4. Nature and characteristics of immune response
      4.1 General overview
      4.2 Immunoassays to measure anti-HPV antibodies
      4.3 Induction of immunity to HPV VLPs in the female genital tract
      4.4 Description of HPV Vaccine Phase II and III Trials
      Table 3: Comparison of trial protocols for the Merck and the GSK products
      Table 4: Vaccine trials and source publications
      4.5 Immunogenicity of HPV Vaccines in Phase II and III studies
      Table 5: Geometric Mean Titres and Seropositivity from Monovalent HPV 16 Vaccine (Merck product), Gardasil™ and Cervarix™
      5. Immunogenicity in other populations
      Table 6: GMTs in girls, boys and women at t=7 months following vaccination with Gardasil™
      Table 7: GMTs at t=7 months following vaccination with Cervarix™ in younger and older female age groups
      6. Short and long-term vaccine efficacy against persistent infection and disease
      6.1 Trial of HPV 16 L1 VLP, Merck product
      6.2 Trials of Gardasil™
      6.3 Trials of Cervarix™
      Table 8: Vaccine efficacy against infection or disease from HPV viruses covered by the vaccine
      7. Effect of the vaccine on the transmission of the type-specific and related HPV genotypes
      8. Short and long-term population effectiveness (i.e. impact on reduction of burden of disease, including herd immunity)
      Table 9: Vaccine efficacy of Cervarix™ and Gardasil™ in HPV naïve and general populations
      9. Vaccine safety and adverse events
      Table 10: Common adverse events reported in the vaccine trials and product monograph
      Table 11: Causes of death among participants in the Gardasil™ trials
  5. Discussion
  6. Acknowledgments
  7. References

I. Acronyms & Glossary

ACIP

The Advisory Committee on Immunization Practices

ADC

Adenocarcinoma

AGC

Atypical glandular cells

AIS

Adenocarcinoma in situ

ASC-H

Atypical squamous cells, cannot exclude high grade

ASCUS

Atypical squamous cells of undetermined significance

ASO4

Adjuvant containing 500 μg aluminum hydroxide and 50 μg
3-deacylated monophosphoryl lipid A

Baculoviruses

Viruses that attack insects and other arthropods

Capsomeres

Protein units that make up the viral capsid or outer shell

CI

Confidence interval

CIN

Cervical intraepithelial neoplasia; this is subclassified into threecategories (CIN 1, CIN 2, and CIN 3)

CIS

Carcinoma in situ

cLIA

competitive Luminex based Immunoassay

cRIA

competitive Radio Immuno Assay

DNA

Deoxyribonucleic acid

ELISA

Enzyme-Linked Immunosorbent Assay

Epitope

a molecular region on the surface of an antigen capable of eliciting animmune response and of combining with the specific antibodyproduced by such a response (also known as determinant or antigenicdeterminant)

FUTURE

Females United to Unilaterally Reduce Endo/Ectocervical Disease

GMT

Geometric mean titres

GSK

GlaxoSmithKline

HR

High-risk (carcinogenic) HPV viruses: 16, 18, 31, 33, 35, 39, 45, 51,52, 56, 58, 59

HSIL

High grade squamous intraepithelial lesion (CIN 2,3)

HPV

Human papillomavirus

IARC

International Agency for Research on Cancer

Icosahedral

A structure with twenty sides

IL

Interleukin

IM

Intramuscular

INF

Interferon

ITT

Intention-to-treat

LR

Low-risk (non-carcinogenic) HPV viruses: 6, 11, 40, 42, 43, 44, 54, 61,70, 72, 81, CP6108

LSIL

Low-grade squamous intraepithelial lesion (CIN 1)

MITT

Modified intention-to-treat

MPL

Monophosphoryl lipid A

NA

Not available

NACI

The National Advisory Committee on Immunization

NOCD

New onset chronic disease

OCP

Oral contraceptive pills

OR

Odds ratio

PATRICIA

PApilloma TRIal against Cancer in young Adults

Pentamer

A molecule composed of five monomeric units

Prophylactic vaccine

These vaccines are designed to protect an individual against an initialinfection; thus the vaccines are given pre-exposure

Pseudovirion

A synthetic virus that is similar in structure and characteristics to anatural virus except that it lacks the capacity to replicate

PHAC

The Public Health Agency of Canada

RCT

Randomized, placebo-controlled trial

RRP

Recurrent respiratory papillomas

Saccharomyces cerevisiae

Baker’s or brewer’s yeast, also known as the ‘top’ fermentor

SCC

Squamous cell carcinoma

Therapeutic vaccine

These vaccines are designed to treat an existing infection thus aregiven post exposure

trichnoplusia ni

Commonly called the cabbage looper, a pest of plants such ascabbage, broccoli, cauliflower, Chinese cabbage

VaIN

Vaginal intraepithelial neoplasia

VIN

Vulvar intraepithelial neoplasia

VLP

Virus like particles


II.Introduction

In 2006, the first of two vaccines for human papillomavirus (HPV) prevention, Gardasil™, was approved for use in Canada. Gardasil™, produced by Merck Frosst Canada Ltd, is a quadrivalent vaccine product against HPV 6, 11, 16 and 18. The National Advisory Committee on Immunization (NACI) statement on the recommendations for the use of HPV vaccine for the prevention of cervical cancer was released in January 20071. A second HPV candidate vaccine, Cervarix™, produced by GlaxoSmithKline (GSK) Inc in Belgium is currently undergoing the regulatory review process by Health Canada. This is a bivalent vaccine against HPV 16 and 18. A need for a systematic literature review on the characteristics of the HPV vaccines was identified. This review was commissioned by the Public Health Agency of Canada (PHAC).

The purpose of this document is to apply the Erickson, De Wals and Farand framework2 on immunization programs to review the following:

  • the disease burden attributed to HPV 6, 11, 16, and 18; and to identify non-HPV risk factors for cervical cancer; and
  • the vaccine characteristics of Gardasil™ and Cervarix™.

Literature review on HPV 6, 11, 16 and 18: Disease and Vaccine Characteristics
M Dawar1, S Dobson2, S Deeks3

(full PDF version 366 KB)