Human Papillomavirus:

Virus and Vaccine

Krista DeLuca
March 17, 2010
Engl 202c
Section 013
Assignment 3: Technical Definition and Description

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Audience and Scope

The purpose of this article is to inform college aged women about papillomavirus,
more commonly known as HPV, the key features of the virus and the vaccine, and
the reasons why they should get it. An article like this should be found on the
Guardasil, (name brand of HPV vaccine) website or in a basic level biology or health
class. It is important for women age 15-25 to know and understand HPV because it
affects women mostly in this age group.

Introduction

HPV, or human papillomavirus, is a sexually transmitted viral infection that causes

genital warts on the vulva, inside the vagina, or on the cervix. Transmitted by skin-
to-skin contact, HPV infects nearly 50% of all sexually active women. Along with
genital warts, HPV is the cause of virtually all forms of cervical cancer.

This type of cancer is the second leading cause of all cancer-related deaths in
women worldwide, only second to breast cancer. On average, over 450,000 cases
are diagnosed annually, and the mortality rate is around 50%. HPV leads to death
for many women every year, but this can stopped. With new scientific technologies,
a vaccine has been created that has a near 100% efficacy against HPV 16 and 18,
which cause 70% of all cervical cancers. This article will explain the virus and how
the vaccine works.

Virus

Entry and Transmission

HPV enters the body usually during sexual intercourse. In order to initiate infection,
the virus must gain access to the lowest layers of cells in the epithelium, or the
membranous tissue lining the surface of a body cavity. This usually occurs by a
break or micro lesion in the skin.

The virions, or small virus particles, then find cells that they can enter. There are
viral attachment proteins on the surface of the virions that interact with
receptors, which are on the surface of all of the cells in the body. This allows the
two membranes to fuse and the virion can empty its infectious particles into the cell
body. In figure 1 below, the virions are shown entering the body through a micro
lesion in the skin of the vaginal wall.

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 Virion

Epidermis

Figure 1: Human Papillomavirus assembly at the epidermal level. Taken from a lecture by Dr.
Anthony Schmidt, Penn State Microbiology Department.

Each cell has machinery used to replicate itself when necessary, and the virus steals
this machinery in order to produce more virus particles. After many of them are
produced, they all gather at the cell surface and assemble into virions where they
bud off from the cell in order to go infect other cells.

Papillomavirus is no different. It uses the cellular machinery of the basal

epithelium to replicate its own DNA, and produce more virions in order to infect
more cells. It usually takes 10 to 14 days before the virus can travel throughout the
body infecting other cells.

HPV Infection Progression

Most HPV infections tend to be opportunistic, meaning that they will only cause
disease if a person has a weakened immune system. In cases where cancer does
develop, the time between initial HPV infection and malignancy of the cancer takes
about 10 years. This is the reason that most women do not get cancer until after age
25. An extremely high incidence of HPV infection is seen around age 16, soon after
women initiate sexual activity. The incidence then declines around age 20 because
most infections are cleared by the immune system. There is a rise in pre-cancer at

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around age 30, and the incidence of cancer jumps around age 40. This data is
shown in the chart below from the National Cancer Institute.

Figure 2: From the National Cancer Institute, the chart above shows the HPV prevalence in
relation to the age of cervical cancer cases.

Persistent cervical infection (longer than 6 months) of HPV type 16 or 18 causes

high-grade dysplasia in women who cannot clear the infection, which allows the
virus to persist for 10+ years. High-grade dysplasia is a pre-cancerous lesion that
can be treated, if detected, to prevent the development of invasive cancer. High-
grade dysplasia can be detected through a Pap smear, which is given at most
gynecological appointments. The lag time between pre-cancer and cancer is
sufficient for treatment.

Vaccine

There are two types of vaccines that are currently in existence. Both of them use
viral proteins in order to boost the immune system. The prophylactic vaccine is for
uninfected young women and is used to prevent the infection of HPV. The
therapeutic vaccine is currently under development to prevent the progression of
HPV to cervical cancer.

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Prophylactic Vaccine

This vaccine is given to uninfected, healthy individuals in an attempt to prevent

future HPV infections. The goal of this vaccine is to confer long-lasting immunity to
HPV, so that the immune system will be able to clear HPV upon infection. The
capsid proteins, or proteins that make up the capsule surrounding the virion, are
isolated and used as a way to evoke an immune response. These capsid proteins act
as VLPs (Virus-like particles).

Since there is no DNA in these VLPs, the virus cannot replicate

and therefore cannot survive. Another advantage of this vaccine
is that the VLPs maintain their conformation even when removed
from the virion. This means that the immune system will be able
to recognize the virions when a person becomes infected, and
respond very quickly. A response this fast will eliminate the
virus before it even causes symptoms.

This vaccine was originally produced by Merck and is known as

Guardasil. It was approved during the summer of 2006 A vial of
the vaccine is shown in figure 3 on the left.. Another vaccine
known as Cervarix was recently approved for Glaxo Smith Kline.

Figure 3: Taken from the Guardasil website, a vial of Guardasil is shown

to the left. Guardasil is the therapeutic HPV vaccine recommended for
all women age 15-25.

Therapeutic Vaccine

This vaccine is being developed for HPV-infected individuals in an attempt to

prevent the progression to cancer. This vaccine aims to boost the body’s immune
response in order to clear the virus. The National Cancer Institute is currently
conducting research to further the development of this vaccine.

Conclusion

Human papillomavirus is a small DNA virus that infects the epithelial cells. Infection
with HPV is the cause of 98% of all cervical cancers, and is clearly a risk for all
sexually active women. The HPV virions bind to healthy cells and steal their cellular

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machinery in order to replicate themselves. The more virions, the more the disease
progresses. The main idea of this document is to explain to young women how HPV
affects them and how the vaccine can save a future of cancer. The Guardasil vaccine
targets women age 15-25, and women should be vaccinated before they become
sexually active. The prophylactic vaccine uses proteins from HPV to induce a
healthy person’s immune response, so that the virus can be cleared if the person
ever contracts it. Another type of vaccine is under development that would prevent
women with HPV from progressing to cervical cancer. Overall, the vaccine is
extremely important for all young women. The percentage of women with cervical
cancer can be drastically reduced with the existence of this vaccine.

Glossary

Epithelium-the tissue that lines body cavities. It is composed of cells separated into
upper and basal epithelial cells by a layer of connective tissue.

Micro lesion- small tear in the epithelial membrane.

Virion- a small infectious virus particle capable of infecting healthy cells.

Viral attachment protein- proteins on the surface of the virions that allow the
attachment and fusion of the virion to the healthy cell.

Cellular machinery- the tools used by host cells to replicate the DNA within the
cell.

Opportunistic infection- an infection that sits dormant in the body until the
immune system is weakened. Once that occurs, the virus replicates at full force
causing disease.

Dysplasia- when the cells of the cervix begin to form abnormalities. The cells
become distorted.

Capsid proteins- the proteins that make up the capsule that surrounds the virions.
Used to illicite an immune response to the virus.

VLPs- Virus-like Particles.

Works Cited

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Guardasil Website
http://www.gardasil.com/

CDC Database- HPV

http://www.cdc.gov/STD/HPV/STDFact-HPV.htm

NIH Medline- HPV

http://www.nlm.nih.gov/medlineplus/hpv.html

Papillomavirus Lecture
from 10/17/08 by Dr. Tony Schmidt in VB SC 435 at Penn State University