Papillomavirus

GENERAL CONCEPTS:

The Papillomaviruses are small, non-enveloped icosahedral particles containing a circular dsDNA genome.
Papillomaviruses are a member of the Papovavirus family, which is divided into 2 genera:
- Polyomavirus, which contains a 5200 base pair DNA genome and has been employed as a good molecular model system. There are 2 polyoma viruses that cause disease in humans; BKV and JCV.
- Papillomavirus, which contains an 8000 base pair DNA genome, can induce benign tumors of the head and neck, several varieties of skin warts, and cervical cancers.
Human papillomaviruses are trophic for epithelial cells of the skin and mucus membranes. They appear to replicate in the cell nucleus and have two modes of replication:
- Stable replication in basal cells and
- Vegetative replication in more differentiated cells that generates progeny virions.
Human papillomavirus (HPV) is thought to be the most common sexually transmitted disease in the world.
The CDC estimates that there are approximately 6.2 million new cases of sexually transmitted HPV infections annually and that over 20 million people are already infected.

DISTINCTIVE PROPERTIES:

Human papillomaviruses (HPVs) produce epithelial tumors of the skin and mucous membranes. More than 100 HPV types have been detected.
HPV infections may be latent (asymptomatic), subclinical, or clinical. Most HPV infections are latent; clinical infections are usually apparent as warts.
Of the many types of HPV, types 6 and 11 are generally classified as "low risk" because infection with these types has a low potential for producing cancerous lesions. These two types of HPv are thought to be responsible for 90% of all genital warts cases.
On the other hand, HPV types 16 and 18 are classified as "high-risk" because they are responsible for most of the lesions that may progress to cancers, particularly those in the anogenital and/or mucosal category. These two types are thought to be responsible for 70% of cervical cancer cases.
In "low risk" infections, the HPV genome is thought to exist as a separate circular dsDNA molecule, while in "high risk" malignant infections, the genome is incorporated into the host genome. Some of the viral proteins inactivate host cell tumor suppressor proteins, and this may lead to carcinomas.

PATHOGENESIS:

Clinical HPV infections may be described as:
- Nongenital cutaneous,
- Nongenital mucosal and
- Anogenital.
Nongenital cutaneous diseases include common warts, plantar warts, flat warts and other skin lesions.
Nongenital mucosal diseases include resiratory papillomatosis, laryngeal papillomas, conjunctival papillomas, carcinomas and others.
Anogenital diseases include a variety of warts as well as cancers of the cervix, anus, vagina and penis.

HOST DEFENSES:

Host defenses against the papillomaviruses are not entirely understood, but a variety of mechanisms probably contribute.
The efficacy of the new vaccine, however, suggests that humoral responses are protective.

EPIDEMIOLOGY:

Papillomaviruses are widespread and warts are common in children and young adults.
Humans are the only host for HPV and infections are generally transmitted by direct contact. However, the virus can survive for extended periods (months) outside the host, and this may provide another means of transmission.
While there is a strong correlation between HPV infection and certain forms of cancer (e.g. cervical cancer), infection alone does not result in maligancy; rather, additional factors such as radiation, immunosuppression, or tobacco use are involved.

DIAGNOSIS:

Clinical: Warts of the skin, oral cavity and genital area are generally diagnosed by appearance.
Laboratory: Microscopy of wart scrapings shows a characteristic histologic appearance. Molecular techniques (nucleic acid hybridization) can be used for other HPV infections.

CONTROL:

Sanitary: Avoidance of contacts but this is not really practical.
Immunological: In 2006, the first vaccine developed to prevent cervical cancer and genital warts in women due to HPV was approved. This vaccine, Gardasil^©, can be administered to females aged 9-26 years of age through a series of three shots over a six-month period. The vaccine is a quadrivalent, recombinant viral protein suspension that protects against infection by types 6, 11, 16 and 18. The vaccine has been shown to be safe and nearly 100% effective.
Chemotherapeutic: Warts can be treated by freezing, cauterization, surgery, laser vaporization, etc.

Papillomaviruses