Human Papilloma Virus

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Human Papilloma Virus

• Basic biology, infection, and psychological
  effects.

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What is HPV?

• Papillomaviruses are small, approximately 52-55nm
  in diameter. 
• They are non-enveloped, icosahedra particles.
  This shape is made up of 12 pentameric and 60
  hexameric capsomers arranged on a T7 lattice. 
• Their carpsid is composed of two proteins, a
  major (L1) and minor (L2).

SEM image of a Human Papilloma Virus and a
computer model showing the structure of the
virus.
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• They are DNA viruses.
•  
• HPV is part of the family known as Papovaviruses,
  which was named for its three main members
  PApillomavirus, POlyomavirus, and simian
  Vacuolating Agent. They are found in many
  vertebrates, and exhibit high species
  specificity.
•  
• This family contains two genera of oncogenic
  viruses, Papilloma and Polyoma viruses.
• The Papillomavirus genome is circular, d/s DNA
  approximately 8,000bp in size.

Many of the HPV genomes have been sequenced and
have a genetic organization similar to that of
HPV-16, one of the oncogenic strains.
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How Does HPV Work?

• HPV infects the basal cells of the dermal layer,
  and early gene expression occurs in these cells. 
• Late gene expression and high copy DNA synthesis
  occurs only in terminally differentiated
  epidermal cells.
• This implies a link between differentiation and
  gene expression, although the nature of this link
  is unknown.
• Some strains of HPV are able to transform host
  cells on their own, whereas others require
  cofactors.

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Expression of the Papillomavirus genome is
very complex and not well understood, because it
has at least seven promoters, exhibits
many alternative splicing patterns, and has an
unknown link to cell differentiation.
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HPV Infection OutcomesE6 and E7 interact with
many cellular proteins, which influence the
outcome of infection.
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How Does HPV Cause Cancer?

• In high-risk HPV strains 16,18,31,39,45 and 59
• Protein E6 interacts with p53 in the host cell
  and promotes its degradation via the ubiquitin
  dependent pathway.
• Protein E7 complexes with retinioblastoma protein
  (Rb), thereby inactivating it.
• Rb and p53 are both tumor suppressors, involved
  in DNA repair and cell death.

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HPV and Cervical Cancer

• In 1995 a study by the International Biological
  Study on
• Cervical Cancer more than 1,000 specimens of
  invasive
• cervical cancer were tested for the presence of
  HPV via a
• polymerase chain reaction-based assay and found
  that
• HPV DNA was present in 93 of the tumors, with no
  difference in presence across the 22
  participating countries.
• HPV-16 was present in 50 of specimens.
• The other strains present included 18, 45, 31,39
  and 59 in descending order of prevalence.

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Can HPV Cause Other Types of Cancer?

• A 2005 study entitled Sensitive detection of
  Human Papillomavirus in cervical, head/neck, and
  schistosomiasis-associated bladder malignancies
  found that
• Virtually all tested cervical cancers and
  schistosomiasis-associated bladder cancers, and a
  plurality of head/neck cancers are associated
  with HPV DNA in the tumor.
• HPV DNA was present in 35of head and neck
  cancers analyzed (253 samples).
• HPV DNA was present in 98of cervical cancers
  analyzed.
• HPV DNA was present in all 27 samples of
  schistosomiasis-associated bladder cancer
  analyzed.
• In another study, HPV DNA was found in 25 of 29
  samples of breast carcinoma. Strains 11 and 6
  were most prevalent.

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The Bad News

• Cervical cancer is the second leading cause of
  cancer death among women world wide.
• Reliable testing of men has yet to be developed.
• An estimated 75of women in the U.S. will be
  exposed to HPV at some point in their lives.

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And Now The Good News

• 70 of women infected with HPV clear the
  infection through natural means within two years.
• It may take 10 to 15 years for an HPV infection
  to develop into cancer.
• Vaccines are currently in development against
  oncogenic strains.

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Vaccine Development

• In the August issue of The Journal of Virology
  Johns Hopkins Medical Institute published a paper
  entitled Development of a DNA Vaccine Targeting
  Human Papillomavirus Type 16 Oncoprotien E6. In
  it they liked DNA encoding CRT to an 10-mer E6
  peptide, in varying combinations. They then
  vaccinated and boosted groups of mice with
  pcDNA3-E6, pcDNA3-CRT, pcDNA3-CRT/E6, or
  pcDNA3-CRT/mt E6. One week after the last
  vaccination they inserted 50,000TC-1 tumor cells
  subcutaniously.

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Reported Effectiveness of Vaccine
In addition to the above results being shown in
vivo, the presence of E6-specific CD8T cells
was demonstrated, and deemed necessary for an
appropriate anti-TC-1 tumor response.
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Capsid Protein Antigen-based Vaccine

• In addition, work is being done on a live oral
• adenovirus vaccine in which a series of
• recombinants are constructed that express the
• major capsid protein of HPV. Preliminary
• studies on oral vaccination with VLPs
• composed of recombinant HPV-L1 shows a
• complete prevention against persistent
• HPV infection.

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Stress and Anxiety Associated With a Positive Pap
Smear

• Surveys of women who have received a borderline
  or mildly diskaryotic pap smear, resulting in an
  HPV positive diagnosis show extremely high levels
  of stress and anxiety.
• Women who undergo a colostomy and come up HPV
  negative have reduced levels of stress and
  anxiety, but report still worrying that it might
  come back and give them cancer.

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Why Does Anxiety Persist After an HPV Negative
Re-evaluation?

• Women report not feeling well informed.
• They demonstrate an unrealistic expectation of
  the risks associated with HPV.
• They report not understanding medical procedures
  preformed on them.
• Young women report the highest levels of stress
  and anxiety due to abnormal pap smears.

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How to Reduce Stress After Receiving an Abnormal
Pap Smear

• As we have all learned stress negatively effects
  the ability of the immune system to clear
  infection. It is therefore especially important
  for women with HPV to minimize stress.

Meditation may ease anxiety.
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• Yoga or meditative practice may help ease anxiety
• Gardening or other outdoor activities can elevate
  mood and keep your mind busy.
• Participation in sports can alleviate anxious
  energy and give you an endorphin rush.
• If necessary, take a step back from high-stress
  commitments, such as work or volunteer efforts
  all youve got is your health.
• Support your immune system via herbal remedies.
• Most importantly, educate yourself on procedures
  and research on HPV as much as possible. This
  will allow you to feel more confidant about your
  choices and future, as well as give you a more
  accurate perspectives on the risk of actually
  developing cancer.

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Carlys Suggestions on Immune System Support.

• Things to Do (or Not Do)
• Drink plenty of water.
• Avoid doing things that might compromise your
  system drug/alcohol use, sleep deprivation, or
  exposure to sick people.
• Do not have unprotected sexual contact, even with
  long term partners you could be re-infecting
  each other.
• Wash your hands regularly.
• Get plenty of fresh air.
• DO NOT SMOKE!
• Sleep as much as you can stand to.
• Relax via deep breathing I suggest breathing in
  and out eight counts each while imagining the
  virus particles in your body being expelled or
  washed away by the power of the breath. It sounds
  funny I know, but just try it, okay?

• Herbal Remedies
• Echinacea root tea is especially good.
• Garlic on an in everything if your stomach can
  handle it.
• Avoid dairy at all costs, especially non-organic.
• Goosegrass as a tea or tincture to support
  lymphatic system function. For lymphatic
  cleansing a day of fast followed by two days of
  fluid food only that means fruit and veggie
  juice, not milk shakes and beer.
• Bearberry, Yarrow, and Couchgrass can be used in
  combination as an infusion to clear the urinary
  tract of microbes.
• Blue Flag, Burdock and Sarsaparilla are
  especially good for infections of the
  reproductive tract.
• A bitter, such as wormwood or strong coffee, may
  be used to stimulate a gut meditated immune
  response.

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Bibliography

• Papovaviruses www.tulane.edu/dmsander/WWW/335/P
  apovaviruses.html
• Papillomavirus web.uct.ac.za/depts/mmi/stannard/
  papillomavirus
• Psychological impact of human papilloma testing
  in women with borderline or mildly diskaryotic
  cervical smear test results cross sectional
  questionnaire study. May 29, 2004, www.bmj.com.
  Maissi et al.
• Womens uncertainties, coping, and moods
  regarding abnormal papanicolaou results.
  University of Wisconsin-Madison. October 8, 1999.
  Lauver et al.
• Womens experience of coping with a positive Pap
  smear a register-based of women with two
  consecutive Pap smears reported as CN1. Acta
  Obstetricia et Gynecologica Scandinavica August
  2003. Idestrom et al.
• Adverse psychological consequences of positive
  cytological screaning. Fox Chase Cancer Center,
  September 2004. Lerman et al.
• Viable adenovirusTranscriptional unit. PNAS,
  March22, 2005. Berg et al.
• Progress on new vaccine stratagies against
  chronic viral infections. Journal of Clinical
  investigation, August 16, 2004. Berzofsky et al.