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Papilloma virus Computer colorized EM image. All 72 capsomeres are pentamers of the major
structural protein. Copyright Dr Linda M Stannard, 1995 (used with permission)
 HPV comprises a group of small
viruses with a double stranded
DNA genome of about 8000 bp.
 With over 100 different types, HPV
infects epithelial cells and cause
lesions ranging from external warts,
cervical lesions, and cancer.
HPV’s are classified into low risk or high risk type:
1. Low-risk types 6 and 11 are mostly associated with genital
warts, and only rarely associated with cancer
2. High risk types 16, 18, 31, 33, 35 are associated with cervical
tumors (pre-cancer and malignant):
HPV 16 is the most prevalent type in both low grade and
cervical tumors , with HPV 16 DNA found in >99% of
cervical cancer.

HPV’s are contained within five evolutionary groups:
Alpha, Beta, Gamma, Mu, and Nu.

Alpha group contains HPV types that infect the cervix and
contains over 60 members.

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Beta, Gamma, Mu, and Nu primarily infect skin
90% of currently classified HPV’s belong to the Alpha or
Beta group
HPV infects basal cells of the epithelial lining. These are actively
dividing cells that will mature into squamous epithelial cells.

Infection occurs in the basal cell layer and results in the
establishment of viral plasmid that does not integrate into host
DNA

Stimulation of cell growth: is caused by HPV oncoproteins E6
and E7 which drive the cell into S-phase.

Basal cells normally exit the cell cycle, but E6 and E7 viral
proteins override the normal cell cycle control in infected cells
Productive Infection
Abortive Infection
Tightly regulated gene expression
Viral gene expression is de-regulated
Results In cervical warts
The ‘normal’ life cycle of the virus
is no longer complete; no new virus produced
Produces new infective viruses
Inactivation of major tumor suppressor proteins
abnormal cell division
precursor to cancer
This is normal cervical squamous epithelium.
The squamous cells show maturation from basal
layer to surface.
http://library.med.utah.edu/WebPath/FEMHTML/FEM003.html
This is cervical squamous dysplasia at high magnification
extending from the center to the right. The epithelium is
normal at the left. Note how the dysplastic (abnormal)
cell nuclei are larger and darker, and the dysplastic cells
have a disorderly arrangement.
http://library.med.utah.edu/WebPath/FEMHTML/FEM008.html
At high magnification, areas of neoplastic (tumor) squamous cells
http://library.med.utah.edu/WebPath/FEMHTML/FEM011.html
p53:
1) activates p21 Cdk inhibitor
inhibits Cdk-cyclin
inhibits
cell cycle progression
2) Apoptosis
pRb
binds and inactivates transcription factor E2F
CyclinE
inhibits cell cycle progression
inhibits Cdk2-
Viral Protein
E1
E2
E4
E5
E6
E7
Function
Initiation of DNA replication- viral genome amplification
Transcriptional regulation-viral genome amplification
Role in genome amplification not fully understood
Transmembrane protein found in the ER- involved in
EGF-mediated receptor signalling
Binds to and mediate p53 tumor suppressor protein
degradation, activates telomerase
Binds to and degrades pRB and mediates E2F
expression of cellular proteins required for S-phase
progression. Binds to and inactivates p21
L1
Formation of infectious virions
L2
Allows genome packaging to begin
Stage
Infection of basal cells:
Expression of viral proteins
Viral DNA transferred to nucleus by L2 capsid
1. Genome maintenance
E6/E7
E1/E2/E4/E5
2. Genome maintenance
Cell Proliferation (growth)
E6/E7
E1/E2/E4/E5
3. Genome Amplification
E6/E7
E1/E2/E4/E5
4. Virus Assembly
Virus release
E6/E7
E4/L1/L2

Cervical tumors are most often caused by HPV and
characterized by the appearance of abnormal squamous cells
with an enlarged nucleus

CIN is diagnosed by increasing severity:
CIN 1- mild-moderate
CIN 2- moderate-severe
CIN 3- severe- CIS ( carcinoma in-situ)

Approximately 20 million people are currently infected with
genital human papillomavirus (HPV) in the United States
(U.S.).1

Every year, about 12,000 women are diagnosed with cervical
cancer, and almost 4,000 women die from this disease in the
U.S.3 About 1% of sexually active men and women in the U.S.
have genital warts at any given time.4
QuickStats: Prevalence of HPV* Infection† Among Sexually Active
Females Aged 14--59 Years, by Age Group --- National Health and
Nutrition Examination Survey, United States, 2003--2004
* Human papillomavirus.
† Determined by DNA extraction from self-collected cervicovaginal swabs.
§ 95% confidence interval.
Among sexually active females (i.e., 57% of females aged 14--19 years and 97% of those aged 20--59 years), the prevalence of HPV infection was highest for those in the youngest age groups (i.e., approximately 40% in those
aged 14--19 years and 50% in those aged 20--24 years). Prevalence declined substantially after age 24 years.
SOURCES: National Health and Nutrition Examination Survey, 2003--2004. Available at http://www.cdc.gov/nchs/about/major/nhanes/nhanes2003-2004/nhanes03_04.htm.
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Figure 43. Human papillomavirus (HPV) — Prevalence of high-risk and low-risk types among females 14 to 59
years of age reported from a national survey, 2003–2004
Note: Error bars indicate 95% confidence intervals. Both high-risk and low-risk HPV types were detected in some
females.
SOURCE:
National Health and Nutrition Examination Survey JAMA, 2007, 297;813–819 Copyright © 2007, American Medical
Association. All Rights reserved.

In June 2006 the FDA licensed Gardisil, the first vaccine
developed to protect against genital warts and cervical
cancer.

The vaccine has been widely tested in females 9-26 around
the world.

This prophylactic vaccine works by preventing four HPV
types: HPV 16 and 18, which cause 70% of cervical cancers,
and HPV 6 and 11, which cause 90% of genital warts. The
vaccine has no therapeutic effect on HPV-related disease.