Human Papillomavirus

Human Papillomavirus
The human papillomavirus (HPV), also called for HPV Human papillomavirus is a DNA virus belonging to the family of Papovaviridae. He is responsible for sexually transmitted most frequently since the estimate of people infected by this virus is between 10 and 30%.

There are over 200 genotypes of HPV. Some genotypes are transmitted through sexual contact and infect the genital mucosa, while others are transmitted by skin contact and infect the skin.

The clinical manifestations of the best known of the contamination of sexual genital warts (also known as "genital warts," or "warts" or "rooster combs), already described by Hippocrates. But the seriousness of this infection is that certain genotypes are mandatory factor for cervical cancer of the uterus, allowing a glimpse, through vaccination against the virus, hoping to one day wipe out this cancer.

Clinical manifestations of cutaneous HPV infection include common warts and plantar warts.

Finally, the transmission may be from mother to child during delivery, although this rarely happens.

Papillomavirus; non-enveloped virion, the capsid is composed of cubic symmetry 72 capsomers in icosahedral structure of 55 nm in diameter, double-stranded DNA, circular, closed, replication in the cell nucleus. Naked virus, it is particularly strong in the external environment (cold, organic solvents, detergents). Its genome consists of 8000 base pairs.

* Viruses with tropism for squamous epithelium
* The human papillomavirus are primarily in the ╬▒-papillomavirus genus. There are over 200 genotypes. 120 have been identified and sequenced. They have a narrow host specificity (for a species) and a specificity of tissue.
* They are designated by numbers according to their historical chronology of discovery
* There are three main groups:
o types and genital mucosal potential carcinogen high: HPV-16, 18, 31, 33, 35, 45, 51, 52, 58 ...
o types and genital mucosal low potential carcinogen: HPV-6, 11 (papillomas and condyloma acuminata anogenital)
o skin types: HPV-1, 2, 3, 4, 5, 7, 8, 10, 27, 57, 60, ...

The genome of genital viruses encode eight genes (and as much protein)

Human papillomaviruses are often present on normal skin of healthy subjects. It speaks of asymptomatic skin infections, which appear early in childhood. Most HPV infections are latent or transient. The lesions induced by these viruses regress spontaneously in most cases.

These genital infections were the most studied.
HPV is the leading cause of sexually transmitted infections (STIs) in the United States. Although its prevalence is high (almost 25% of females after puberty, it is particularly important in young women under 20 years):

* More than half of low-grade lesions regress spontaneously within a few years, 10% of lesions progressing to high grade
* About one third of high-grade lesions regress spontaneously, 5% progressing to cancer,
* Total less than 0.3% of infections progress to cancer.

It thus considers that the majority of sexually active people have had at least one HPV infection in high potential carcinogen in their lives, especially during the early years of sexual life.

The virus is transmitted by direct contact, oral, self-inoculation (transmission of warts is favored by scratching) and indirect contact (contaminated objects and surfaces - the local showers, pools, etc.. Promote the spread of warts foot) transmission is sexual in the case of ano-genital warts; transmission of laryngeal papilloma occurs from mother to child during passage through the birth canal.

* From 1% to 2% of men and women infected present clinically exophytic warts visible.
* The incubation period is about 2 to 3 months for warts exophytic, but it can be calculated in years in the case of cancer or precancerous lesions.
* The clinically visible exophytic lesions are rarely associated with cancer:
o Only some HPV genotypes are associated with cancers of the cervix, vulva and penis, and anorectal cancer. The DNA of some serotypes of HPV is present in at least 80-90% of cervical dysplastic lesions (neoplasia cervical intraepithelial) and cancers of the cervix (HPV 16, 18, 31, 33 or 35). The genotypes (HPV 6 and 11) that cause most often exophytic warts were not associated with these cancers.
* Perinatal transmission of symptomatic infection appears rare.
* When it occurs, infection is associated with genital lesions and lesions of the vocal cords. It ignores the duration of the incubation period. Usually, the perinatal transmission becomes clinically apparent during the first 2 years of life.
* Patients infected with HIV often have anogenital warts extended to meet shortly to treatment.
* The progression to cancer is closely associated with smoking and HIV infection.

Other infections
The human papillomavirus (HPV) is also found in other squamous epithelia, the oropharyngeal mucosa but above the esophageal mucosa. HPV is often observed in benign and malignant lesions where it induces the cells pathognomonic of infection: the Koilocytes.

* Benign tumors of the esophagus.

The benign lesions in the esophagus are papilloma virus (or SCP, squamous cell papilloma).

The involvement of HPV is strongly suspected in view of the existence of a koïlocytose more or less pronounced in these lesions, but the proof is made by PCR in 20% of cases (0% in countries with low risk such as Finland, over 50% in high risk countries such as China during a campaign screening of esophageal cancer.

This suggests that HPV (especially types 6, 11 and 16), it is not sufficient to induce the formation of papillomas, was certainly a role of cofactor in the development of these benign tumors (Chang et al. 1991).

It seems that very few papillomas can progress to squamous cell carcinoma.

* Malignant tumors of the esophagus

Malignant tumors of the esophagus are squamous cell carcinomas, adenocarcinomas grow on them in a Barrett's esophagus. HPV seems heavily involved in the etiology of squamous cell carcinoma of the esophagus (squamous cell carcinoma: SCC): one finds there also Koilocytes.

The first study demonstrating the role of HPV in the genesis of esophageal lesions is an animal study. Highland cattle in Scotland are frequently esophageal papillomas; experimentally papillomatosis was induced by the bovine papillomavirus 4 (BPV4). These animals frequently develop cancer of the esophagus, and 96% of animals with this cancer are also carrying BPV4-induced papillomas. It was shown that ingestion of ferns (which are rich in carcinogenic and immunosuppressive drugs, eg azathioprine) was a factor in the malignant transformation of papillomas.

In men, HPV is often found by PCR in the CSC (from 25% to 40% in studies) type 6, 11, 16, 18 and 30, but most often type 16. As for the benign lesions, found more frequently in HPV cuts CSC from countries at high risk or high risk than in those from low-risk countries.

It is now accepted that HPV is a cofactor of carcinogenesis in relation to squamous cell carcinoma of the esophagus, acting in synergy with other risk factors (nitrosamines, mycotoxins, opium smoking, excess tobacco or alcohol ...).

Clinical manifestations of genital damage
* The infection can be subclinical or clinical, but it is usually asymptomatic.
* In women, the cervix is the most common site of genital HPV infection. The infection often multiple sites (cervix, vagina, vulva, etc..).

Flat condyloma
Keratinized lesions slightly elevated.

* The growths on the skin or mucous membranes of the anogenital region are often multiple and polymorphous appearance with exophytic outgrowth between one finger-or cauliflower-like and papular lesions.
* The natural history of infection is characterized by a fluctuation in the size and number of warts and, in many cases, their eventual disappearance. The size and number of warts may grow during pregnancy.

Dede Koswara, Indonesian fisherman, was long nicknamed the "Tree Man" because of the spectacular affection he has developed and is carrying a genetic disorder called epidermodysplasia verruciformis, which makes it impossible to develop an immune response towards Screw papillomavirus in cutaneous tropism. His whole body was covered with protuberances having the appearance of fungi or roots, making her skin appear as bark.

Dede Koswara was finally made in 2008, and expects a return appearance and a normal life, although a recurrence can not be excluded.

* Diagnosis is made by direct examination of the external genitalia, using a magnifying glass or colposcope may be helped by applying acetic acid to 5%, and Lugol.
* The diagnosis of genital infection with HPV 16 or 18 is by looking for viral DNA (by "hybrid capture" by RNA probes, or gene amplification (polymerase chain reaction or PCR), in vitro) during of conducting a smear. However this test is based on the detection of DNA viruses. A positive result shows only the virus but the positive predictive value for the risk of developing cancer is low (10 to 20%).
* The diagnosis of genital HPV infection is also looking for viral mRNA (Nuclisens EasyQ HPV). The expression of viral oncoproteins E6 and E7 initiates the process of cancer by affecting cell cycle control. This new test is based on the detection of mRNA of E6 and E7 oncoproteins in human cells. The mRNA of oncoproteins E6 and E7 are markers predictive of the activity of oncogenic HPV to identify women at risk of developing HSIL (CIN2 / 3) and carcinoma of the cervix. The principle of this test is based on the amplification and detection of E6/E7 mRNA by NASBA (Nucleic Acid Sequence-Based Amplification) in real time.
* There is no serological test on the market.

Treatment and support
There is no treatment to cure an HPV infection. The destruction of visible lesions may however be made more or less simple. The lesions of the cervix are treated by cryotherapy (application of liquid nitrogen) by the laser or through surgery or by removing a portion of the cervix (cone biopsy) or by removing it entirely. Local treatments are also possible (podofilox solution or gel 0.5% Podophyllin 10-25% which must be applied by a doctor).

Other treatments stimulators of immunity are currently under development.

After treatment, it is possible that the virus is still present even if the warts have disappeared. It is therefore important to monitor the recurrence of lesions for several months after resection.

* The cell-mediated immunity may help eradicate HPV over time(?).
* The warts are often very persistent and recurrent. However, we observed a complete disappearance of external genital warts in 80% of patients who present. Cervical lesions disappear in about 90 to 95% of cases.

* Condoms reduces much of the transmission of HPV and the incidence of persistent HPV infection (which means that regular use of condoms results in a regression of preexisting lesions more frequently than if not used). There may, however, contamination by contact with skin areas not covered by the condom.
* In October 2005 came a vaccine against HPV types 6, 11, 16 and 18. This vaccine called Gardasil is likely to prevent precancerous lesions and cancers of non-invasive cervical cancer caused by HPV type 6, 11, 16 and 18.

The conferred immunity lasts at least five years. Its effectiveness is almost complete (98%) among women not infected by a virus in the vaccine. It does not seem effective, or for other genotypes, neither for women already infected. Efficiency is not known beyond five years, partly because of the length of developing cancer of the cervix.
Vaccination especially for adolescents before their first sexual intercourse or at age 14 years, and it recommends that the CSHPF which advocates a routine vaccination at this age.
Vaccination is not without interest at a later age, in women who have never been infected by at least one of the viral types in the vaccine, in which case, the vaccine has the same protective efficacy than the younger subjects.
Vaccination does not preclude the continuation of screening for cervical cancer of the uterus or the use of condoms.

See also Cervical Cancer