HUMAN PAPILLOMAVIRUS
Who is affected by HPV infection?
The majority of infections occur in people in their early teens and twenties, with incidence declining as people age. One study found that 40% of college age women visiting the campus health clinic were infected with the virus. Sexual activity is a risk factor for the disease, as is immune suppression.
Trends
in Physician's Office Visits
What are the diseases induced by HPV?
|
DISEASE |
STRAIN |
|
Common warts |
2, 7 |
|
Plantar warts |
1, 2, 4 |
|
Flat cutaneous warts |
3, 10 |
|
Anogenital warts (Condyloma acuminatum) |
6, 11, 42,43,44, 55 and more |
|
Genital malignancies |
16, 18, 31,33,35, 39, 45, 51 |
|
Epidermodysplasia verruciformis |
>15 strains
|
|
Focal epithjelial hyperplasia (oral) |
13, 32 |
|
Oral Papillomas |
6, 7, 11, 16, 32 |
Common Warts, Plantar Warts and Flat Cutaneous Warts
(This is a picture of common warts with permission from the University of Indiana Department of Pathology)
Common Warts are found in areas which are exposed and frequently rubbed, such as on the hands and knees. They are raised and rough.
Plantar warts are painfuldeep warts found often on the bottom of the foot, and other areas which bear much weight.
Butcher' warts is caused by and is frequently found in butchers, who are exposed to the virus when cutting meat.
Flat or Plane Warts, common in children, are typically located on the arms, knees and face. They are smaller and less rough than other warts.
Treatment:
All current therapy acts to remove the region of
the wart. Medicines that are used are 80% Trichloroacetic acid,
liquid nitrogen, podophyllin, podophyllotoxin, 5-fluorouacil,
intralesional interferon, laser, LEEP elcetrocautery, and cold
scalpel excision. Some researchers also suggest that hypnotherapy and
mental imagery are effective treatment. (See Morris, John
"Hypnotherapy of Warts Using The Simonton Visualization Technique: A
Case Report" Americal Jounal of Clinical
Hypnosis. 27(4) 237-240 1985. )
Genital Warts
Genital warts are, perhaps, the most common disease manifestation of HPV. They are small lesions in the genital and perigenital areas that can be visible to the naked eye, but identification may also require appropriate magnification with a magnifying glass or colposcope. Most HPV infections, however, are subclinical. It is for this reason that it the incidence rate has been estimated at 100 times the current reporting rate. Some refer to this as "the tip of the iceberg" analogy. Genital warts has gained a lot of medical attention in recent years because the several dozen HPV strains that cause the condition are associated with genital cancer. Typically, these strains are grouped into categories of "low-risk" strains, "intermediate-risk" strains, and "high-risk" strains.
Treatment
HPV persists in the body, but genital warts can be treated using a variety of methods. There are cytotoxic agents which include Podophyllin and Trichloroacetic acid, surgery and medical treatments like interferons and retinoids.
Epidermodysplasia Verruciformis
People with a rare autosomal recessive hereditary
immunodeficiency condition may develop this dermatological disease.
The disease has two presenting symptoms: flat warts (caused by HPV 3
and 10) and scaly patches (caused by 20+ rare strains) Patients with
this disease often develop skin cancer after exposure to ultravioulet
light.
Here is a picture from the Dermatology Online Atlas in University of
Erlangen-Hurnberg, Germany.
Larryngeal papillomas
25-35% of oral cancers are associated to oral papillomas. In particular, HPV 7 is found in some HIV positive individuals.
Cervical cancer is highly associated with HPV strains 16 and 18. Ninety percent of cervical cancers contain HPV DNA (usually HPV 16, 18). The vulva, vagina, penis and anus also can be affected by these carcinogenic strains.
In the US, the disease occurs in 8/100,000 patients. The introduction of Pap smears greatly reduced the rate of the disease (Some say by 70%). In developing countries, where Pap smears are not available, rates of cervical cancer are really high. (For more information about this global health problem read this WHO press release).
Pap smears (reccomended yearly for women) detect abnormal cells (Pictures of normal vs. abnormal cells) which evince cervical dyplasia (or cervical intrepithelia neoplasia). Three stages occur in the development of the cancer; they are identified as CIN-1, CIN-2, and CIN-3 (carcinoma in situ).CIN-3 is the beginning stages of cancer.
Not all women infected with HPV get cervical cancer, however. For some, an initial humoral response (perhaps against capsid proteins) prevents them from even getting infected with HPV. Others may have cell-mediated immune responses against the proteins E6 and E7.
Further, women who use tobacco have higher rates of cervical cancer. Smoking is considered a cofactor for the disease to develop.
How is HPV speculated to cause cancer?
HPV DNA integrates into the host genome.
The proteins E6 and E7 are produced from the resultant DNA.
E6 binds and degrades p53 (a tumor suppressor gene).
So what? Normally, if the cell DNA is damaged, p53 is in charge of stopping the cell cycle so the DNA can be repaired. Now, if the DNA is altered, the cell keeps replicating. The mutation rate of the cell increases!
E7 binds and degrades retinoblastoma (another tumor suppressor gene).
Hm, sounds familiar. Retinoblastoma normally keeps the cell from growing too fast or responding to growth stimulators. This inhibitory factor is now lost!
And so, without these two mechanisms to slow down cell growth and prevent mutation. . .
Malignant Transformation Occurs!
(Links about Pap Smears, Cervical Cancer and HPV)
What are Prevention Methods?
Preventing HPV infection is very difficult. Most infections are asymptomatic, yet transmissible. However, condom use can reduce transmission, at some levels, and reduced sexual partners can also reduce one's chances of contracting the HPV.
Cervical cancer, however, can be prevented, or can be detected at very early stages with regular Pap smears (annually, or bi-annually if directed by a physician). Also cofactors such as smoking and number of sexual partners can increase the risk of actually developing neoplasias or malignant transformations.
Vaccines
Vaccines have yet to be developed for Human Papillomavirus. Currently, researchers are working on two methods of vaccine development: the prophylactic vaccine and the therapeutic vaccine.
Prophylactic Vaccine Strategy:
The prophylactic vaccines are using L1 and L2 capsid proteins to induce production of "conformationally-specific" antibodies that have been shown in animal models to block HPV infection. Lone L1 and L2 proteins self-assemble into a capsid that is identical to the complete virion. So, a antibody-mediated response is mounted before the body actually comes into contact with the live virion.
Therapeutic Vaccine Strategy:
Therapeutic vaccines are being developed to protect HPV-positive persons against tumor development. For these vaccines, researchers are targeting the activity of the E6 and E7 oncoproteins. Recombinant expression of BPV and E6 or E7 is being used to block tumor development.
Coping with HPV
HPV can cause not only unsightly, but often psychologically harmful effects. Support groups are available. If you have HPV, and are interested in trying an experimental drugs, the Mayo Clinic has several clinical trial you may be interested in participation in. (Mayo Clinic Clinical Trials), as well as several other pharmaceutical companies.