HPV 16 oncogenic type: as manifested, treatment with drugs and alternative means

All one and a half hundred strains of human papillomavirus (HPV or HPV) have a digital designation. If most of them cause growth of warts in different parts of the body and are HPV serotype of low risk of malignancy, then type 16 HPV (and even more than a dozen strains) is considered carcinogenic and is defined as a high-risk serotype.

[1], [2], [3], [4], [5], [6]

Structure HPV type 16

Icosahedral nucleocapsid of the papilloma virus contains fragments of double-stranded DNA, for the replication of which it needs foreign proteins. HPV obtains access to them, penetrating into human cells through endocytosis of the cellular receptor, and forms its membrane from the proteins of cell membranes. In this case, type 16 virus is characterized by insertion into the genome of the cell, and penetration into its nucleus is a necessary condition for replication. But if the immunity in humans is strong enough, the virus remains in the cell in a so-called episomal form.

Replication of HPV 16 occurs in the epidermis, more precisely, in the basal cells of the stratified squamous epithelium of the stratum corneum and cells of the flat nonkeratinized epithelium of the mucous membranes, in which the process of cellular mitosis and migration is constantly occurring. Obviously, a more loose intercellular matrix of the epithelium of the genitals, perineum and perianal region, as well as local increased humidity, is a favorable factor for this virus.

In addition, the cells of the superficial epithelium of these regions are often subjected to microtraction (abrasions), and many experts are sure that HPV 16 lesion with its activation occurs only if the epithelial barrier is broken. Moreover, as an opportunistic infection, HPV uses the fact that cellular immunity can significantly weaken the bacteria that are often present in the anogenital region, in particular when chlamydia or ureaplasma and HPV 16 are combined, as well as other viral infections, for example herpesviruses.

The HPV pathogenesis induced by malignancy consists in the interaction of the primary viral oncoproteins E6 and E7 with the nuclei of the anti-oncogene cells (tumor suppressor proteins p53 and pRb), which causes these cells to degrade and cease to perform their protective function. And then the neoplastic process begins: the cell cycle changes, the growth of cells is lost, the rate of their proliferation increases, mutations occur in the cell structures. As a result, this leads to the development of dysplasia or a tumor.

[7], [8], [9], [10], [11], [12],

Pathogenesis

HPV is an epitheliotropic DNA virus of direct action, that is, by penetrating into the cell of the epithelium or mucous membrane, the virion is integrated into the genome of the human cell and unites with it, forming a special latent form. In this form, he can stay in the cells for a very long time without causing any symptoms (for more details, see the section "Pathogenesis").

HPV infection is very common, but 80-90% of people have immunity that can cope with it on their own, and a person may not even suspect that they were infected with this virus.

But sometimes the virus displays its presence openly. More than 30 strains affect the mucous membranes of the genito-urinary tract and the epidermis of the anogenital region. Thus, low-risk serotypes (HPV 6, 11, 42, 43 and 44) can cause  genital warts  with frequent seizure of the perianal zone; they can also provoke the development of respiratory papillomatosis. And with the highest-risk serotypes - HPV 16, 18, 31, 45 - is associated with the defeat of the cervix with a high probability of its development into cervical cancer.

Therefore, as transmitted by HPV 16, it is clear: this is a sexually transmissible, that is, the sexual way (including all variants of sexual contacts). And the hidden HPV, even without external signs, is also transmitted to the sexual partner. And unprotected sex increases the likelihood of infection by 75%. As a rule, two thirds of people who have sexual contacts with an infected papillomavirus partner, genital papillomas may appear within two to three months.

How is HPV 16 transmitted?

Although genital tract is not the only way to spread HPV: all of its serotypes are extremely contagious and can be transmitted by contact with an infected mucosa or dermis. Presumably, the infection is able to get from one part of the body to another: gynecologists believe that the virus can first hit the cervix, and then spread to the vagina and vulva.

A natural question arises, is HPV 16 transmitted via saliva? Viruses associated with benign and malignant lesions of the skin and mucous membranes cause papillomas of the oral cavity, and not less than 90% of cases of type 16 HPV are involved in the development of oropharyngeal cancer - squamous cell carcinoma of the throat. So virologists believe that saliva can play a role in the transmission of infection. Although the specialists of the American Cancer Society claim that the virus does not spread through any biological fluids.

The main risk factors for HPV 16 infection include weakened immunity, early onset of sexual activity, multiple sexual partners, lowering the pH (acidification) of the body, and the presence of inflammatory diseases of the genital area. Smoking and prolonged use of oral contraceptives also reduce resistance to papillomaviruses.

[13], [14], [15], [16], [17]

The incubation period

The incubation period after infection with dermatotropic serotypes of HPV - with manifestation in the form of papilloma or genital warts - varies from several weeks to a year. However, most warts appear in two to three months.

With oncogenic papilloma viruses, everything is much more complicated. The incubation period for HPV 16 - to begin to show signs of malignant transformation of cells of the cervix - long enough. Studies have shown that the average incubation period from the initially identified HPV 16 to the diagnosed low-grade dysplasia (intraepithelial neoplasia) of the cervix is 5 years, and to cervical carcinoma in situ - 12-15 years.

It is believed that in the latent or persistent state this virus can stay even longer, which increases the probability of infection of sexual partners throughout their life. And how many live with HPV 16, depends on whether he showed himself, provoking the development of cancer, or not. But the very presence of this virus - with asymptomatic or subclinical existence in the body - does not affect the duration of life.

It should be borne in mind the widespread latent carriage of HPV 16, which can be detected only by partial genotyping using a polymerase chain reaction - when the patient gives an analysis for STDs. In such cases, according to several foreign studies, the positive result of the asymptomatic presence of the virus can be 27-44%.

Epidemiology

According to some estimates, from 50 to 80% of men and women of sexually active age sooner or later get infected with HPV ...

According to the latest WHO data, two thirds of all cases of precancerous pathological conditions and cervical cancer cause exactly the types of HPV 16 and HPV 18. And experts of the American Cancer Society say that this type of virus is detected in 90% of patients with this diagnosis.

Statistics CDC cites such official figures: in the United States annually there are 6.2 million new infections with all types of HPV; 79 million Americans are infected with papillomavirus, of which 20 million are infected with the HPV 16 virus, and these are people of reproductive age. Up to 20% of patients with genital papillomas and condylomas have other sexually transmitted diseases.

The prevalence of HPV 16 in women (about 18%) is twice as high as in men (8%).

According to the Journal of Virology, every day about 12 thousand Americans aged 15 to 24 years are infected with HPV. Of these, approximately 0.1% is HPV type 16.

Also this virus (in combination with HPV 31) in 23-25% of cases is a trigger of a subset of squamous cell carcinomas of the mouth and pharynx.

[18], [19], [20], [21], [22], [23], [24], [25], [26]

Symptoms

If most people have papillomavirus does not manifest itself, the symptoms of HPV 16 are absent. When activating a persistent infection, its first signs are most often benign epithelial neoplasia - papillomas and condylomas. Different sizes and shapes of  genital warts in women  can occur on the external genitalia, in the vagina, on the cervix, in the perineum, outside and inside the anus.

Diseases caused by HPV 16

Gynecologists draw the attention of their patients to the fact that any allocation of HPV 16 in women appears only in cases of its activation and development of diseases (see below), and the nature of the secretions depends on a number of additional factors. A latently existing infection never leads to the appearance of pathological vaginal discharge.

The localization of  genital warts in men : on the foreskin and head of the penis, on the scrotum, in the urethra, around and inside the anus. Also, condylomas can appear on the mucosa of the mouth, nasopharynx or larynx.

The consequences and complications of HPV 16 in clinical practice are defined as diseases caused by HPV 16. And this corresponds to the pathogenetic principles of medicine. In addition, sex with HPV 16 in both women and men is often difficult and can stop due to serious health problems.

Thus, HPV 16 in women can lead to the development of such pathologies as:

• cervical erosion;
• endocervicitis;
• dysplasia of the cervix;
• cervical cancer;
• cancer of the vulva;
• vaginal cancer;
• anal cancer (most common in HIV-infected people);
• leukoplakia of the oral cavity (including proliferative prostucous leukoplakia);
• squamous cell carcinoma of the throat (oropharyngeal cancer).

HPV 16 in men can provoke development:

• urogenital and anal papillomas;
• condyloma of the rectum;
• squamous cell carcinoma of the penis;
• verrucous (verruxic) carcinoma of the penis;
• Cancer of the skin of the penis -  Bowen's disease;
• Keira's erythroplasia;
• squamous cell carcinoma (among patients with this cancer most people with immunodeficiency syndrome and homosexuals).

Also, one of the most common lesions of HPV 16 in men are tumors that occur at the root of the tongue, on the back of the larynx and on the pharyngeal tonsils.

HPV 16 in children appears as a result of transmission from the mother during labor, but the development of related genital diseases is rare. However, the absence of any signs does not exclude an asymptomatic latent infection, since the virus is able to hide for decades.

Most often, this type of HPV infection of the mucous membranes of newborns is manifested by papillomas in the trachea, bronchi and lungs - respiratory papillomatosis. These papillomas can also grow on the vocal cords, causing  laryngeal papillomatosis.

[27], [28], [29], [30], [31]

HPV 16 and pregnancy

HPV infection does not reduce fertility and does not directly affect the possibility of conception, and the question of whether it is possible to become pregnant with HPV 16 - gynecologists give an affirmative answer.

However, when a viral infection leads to changes in the cervix, they should be treated. Concerning this and the planned conventional conception, and IVF with type 16 HPV. Doctors recommend postponing pregnancy until the treatment is completed.

It is also necessary to take into account the fact that - against the background of physiologically caused immunosuppression and increased blood flow and the number of vessels in the genital area - genital warts during pregnancy (especially between 12 and 14 weeks) can grow faster and cause irritation or other symptoms (swelling, tenderness , burning, bleeding, problems with urination).

The risk of HPV transmission to a child is extremely low, and simply because of the presence of a virus in a pregnant cesarean section is not recommended. Therefore, the answer to the question - whether it is possible to give birth with HPV 16 - is also affirmative.

Diagnostics

The detection of papillomavirus in the body, that is, the diagnosis of HPV 16, is possible only by microbiological molecular methods.

HPV tests include a qualitative test performed by examining a vaginal or cervical smear (which is taken by a gynecologist) with the help of a polymerase chain reaction - HPV PCR; At the same time, a quantitative analysis is performed on HPV 16-PCR / HPV SRS.

The norms of HPV type 16 are relative, since the numerical expression of the number of living virions (more precisely copies of HPV DNA or markers of their genomes - Lg) is 10 ⁵  (100 thousand). Cells of biological material the viral load of HPV 16 is determined. The more their number, the infection activity and the viral load are higher:

• viral concentration (that is the probability of oncology in the development of diagnosed pathology) of a very high level - 5 Lg and higher;
• the number of viruses is of clinical importance (in the diagnosis of an etiologically related disease) - a range of 3 to 5 Lg;
• a slight viral concentration - below 3 Lg;

And using the method of PCR-genotyping, a specific type of papillomavirus is determined, that is, its DNA is determined in comparison with reference (reference) samples. The test can have the designation PCR 16 / DNA HPV 16. Biological material for this analysis is scraping from the mucous membrane of the cervix or its canal. Its significance is that an oncogenic virus can be determined before the PAP-test (Pap smear) can detect any abnormal cells of the cervix.

[32], [33], [34], [35], [36], [37]

Treatment

The first and main question is - is HPV type 16 treated? The second and also important question - what to do with HPV 16?

There is no radical therapy for papillomavirus, as there is nothing to release the body from its presence, and only diseases that are involved in the development of HPV of this type are subject to treatment.

In 2012, the European guidelines for the treatment of anogenital warts (condylomata acuminata) were published, and it was stressed that only surgical treatment (removal of papillomas and genital warts by surgery) produced a positive result in almost all patients.

In addition to surgical resection of neoplasias, hardware methods are used: radio-wave excision, diathermocoagulation, laser ablation, cryodestruction. Read more in the material -  Removal of genital warts

A cauterization of erosion with HPV 16 is performed in the same way as in the absence of this infection, see -  Cauterization of cervical erosion

Algorithms and existing treatment regimens for HPV 16 include drug therapy. And below will be called the main drugs that are most often used in clinical practice.

To reduce the oncogenic load and activate cellular immunity (T-lymphocytes, macrophages, dendritic cells, etc.), immunomodulators are prescribed for HPV 16-preparations containing interferon or its analogues.

It stimulates the synthesis of endogenous leukocyte α, β and γ-interferons alloferon or Allokin alfa. It is administered subcutaneously - 1 mg every two days. In total, such injections with HPV 16 do not more than nine times (usually limited to six injections), but if necessary, after a short break, the course of treatment can be repeated. This remedy is not used for children, pregnant and lactating, and also if there are diseases of an autoimmune nature.

Immunomodulating drug  Isoprinosin  (other trade names - Pranobeks, Groprinosin, Inosin, Novirin) are prescribed two tablets (each 0.5 g) three times a day for two to four weeks. The drug can cause side effects in the form of decreased appetite, headache and joint pain, nausea, abdominal pain, intestinal disorders. Among its contraindications include chronic kidney failure, the presence of stones in the bladder, pregnancy and lactation.

Cycloferon (Neovir) induces the production of interferons by the action of acridoneacetic acid. Produced in the form of tablets, solution for injection and liniment. Tablets are used one to two times a day (before meals) for three weeks. The course of injections (in / in or / m) is prescribed for severe lesions, usually one injection per day. The drug is not used for cirrhosis and pregnancy. Liniment is used topically: by instillation into the urethra or into the vagina.

To the means, increasing the immunity, includes Polyoxidonium (Azoxime bromide) - lyophilizate for the preparation of solution (for IM and / or in administration), vaginal suppository -

Adults (except pregnant women) are injected with HPV 16 twice a week or every other day (one injection in a single dose of 6 mg). Children, the dose of Polyoxidonium is calculated at the rate of 0.1 mg per kilogram of weight; injected once during the day, the course of treatment - 7-10 injections. The vaginal suppository is used in the evening (before bedtime - one suppository per day for a decade).

But the remedy Amiksin is used to prevent influenza and reduce the manifestations of ARI, but DNA viruses are not prescribed.

Candles, gel and injection solution of  Panavir  contain an extract of potato sprouts: the agent is declared to be antiviral and at the same time immunomodulating (in International Pharmacopoeia is not registered).

Dried fruits with green tea extract are not medicines, which, according to the description, are recommended for the prevention of cancer, as well as Indinol (Indole-3-carbinol) containing indole derivatives obtained from broccoli.

Outer - with superficially located anogenital warts of a small size - apply the solution of Podophyllotoxin (Podophilox, Condilin), and Keravort cream (Imiquimod) - once a day every night for a month; if necessary, repeated courses of treatment should take a break. Both drugs are contraindicated in children and pregnant women.

A very common remedy for topical application - vaginal and rectal suppositories from HPV 16:

Genferon (with α2-interferon) - one suppository invaginally (men - rectally);

Viferon (with the interferon, vitamins C and E);

Vitaferon (with interferon and vitamin C), etc. More information in the article -  Suppositories from HPV

But vaginal capsules (not candles) Polizhinaks are designed to treat candidiasis and bacterial infections of the vagina, they are useless in viruses.

Alternative treatment of HPV 16

What does alternative treatment for HPV 16 recommend? Garlic and iodine moxibustion; lubricating them with tincture of propolis with the addition of fresh onion juice; application of a concentrated solution of baking soda or a tincture of green peel of walnuts on kerosene.

It is claimed that external peroxide of hydrogen from HPV 16 or 10% aqueous ammonia (liquid ammonia) can help.

You can try and treat herbs, for example, 5-6 times during the day, lubricate the warts celandine (fresh juice). And since the researchers found immunoregulatory activity and the ability to increase the synthesis of interferon of one of the licorice species - Glycyrrhiza uralensis, it is advised to take an aqueous extract of the root of this plant. In addition, glycyrrhizic acid is present in licorice, which stops the growth of pathogenic bacteria and viruses.

[38], [39], [40], [41], [42],

Prevention HPV type 16

It is easier to prevent than cure. Therefore, sex education should be correct, and sexual contacts - orderly and protected ...

Well, that there is a vaccine against HPV 16 and 18: Gardasil (manufactured by Merck) and Cervarix (GlaxoSmithKline). These antiviral vaccines are effective in blocking the penetration of HPV into the cervical epithelium by generating HPV-specific neutralizing antibodies. But they, alas, can not destroy the already introduced virus. See also -  Vaccination against human papillomavirus (HPV)

Doctors recommend vaccination for girls aged 9-13 and girls under 26 years of age. At the end of 2012, vaccination against HPV was introduced in 45 countries. And in 2013, in Australia, began to vaccinate adolescent boys.

But it is important to realize that the vaccine will not be able to prevent all cases of cervical cancer. So, adult women need to undergo screening gynecological examinations.

[43], [44], [45], [46], [47], [48],

Forecast

The presence of type 16 HPV does not mean that you have cancer: up to 90% of those infected with high or low risk papillomavirus are released from infection within about two years.

In 30% of cases, genital genital warts in women spontaneously regress within four to six months. True, until the end it is unclear whether this immuno-mediated regression eliminates the infection or simply suppresses it for a long time. But in any case the virus ceases to manifest itself.

However, each newly acquired infection can persist as an incurable life-long disease, leading to a significant increase in the long-term risk of cancer in patients and their sexual partners. Many of these cancers associated with HPV 16 can only be manifested after decades.

The question arises - how to live a normal life with HPV 16? Doctors advise to monitor their health and maintain immunity.

[49], [50], [51], [52],