HPV type 33: symptoms, treatment

Today in medicine, various diagnoses and incomprehensible abbreviations that only frighten a simple, unenlightened person are increasingly appearing. A striking example is the diagnosis of HPV type 33. What is this strange diagnosis? Let's look in more detail in all the details.

What it is?

Many have to take laboratory tests. Having received the study, you can read such a frightening diagnosis in a blood test. The first thing that comes to mind is what is it? It turns out that in other words this abbreviation can be called the human papillomavirus. The strain code number 33 is indicated next to it. This is a virus that quite often persists in the representatives of the Europoid race.

The human papillomavirus (HPV) 33, part of the alpha-9 group, occurs in approximately 5% of cervical cancer cases worldwide. [1], [2]

Structure HPV type 33

The structure of the virus is very specific. First of all, it is noteworthy that the size of the virus can vary within a fairly wide range - from 100 to 200 nm. The shell is represented by two layers. The first layer is formed by lipids, the second is represented by a complex of glycoproteins. The components are interconnected by non-covalent bonds.

High-risk HPV genotypes 33

The papilloma virus belongs to the family Papillomaviridae. This is an extensive group of viruses that cause the formation of tumors. 

28 HPV33 variants were identified that formed 5 phylogenetic groups: previously identified lines A1, A2 and B (sub) and new lines A3 and C (sub).

The HPV33 variants were classified into two main lines, A and B. Line A was further divided into two sublines, A1, which includes the prototype sequence [M12732.1 (Cole and Streeck, 1986) [3]  and A2. This classification is based on the determination that the complete genome sequence of the main variant line differs by about 1.0% from another variant line of the same type of HPV, with differences of 0.5–0.9% determining the subline (Chen et al., 2011 ) [4]

A1 sublines are common throughout the world, although the relative frequency varies by region. Sublines A2 were rarely found in Africa and South America, while line B is specific for Africa. Subline C was found only in samples from Africa, and the A3 subline was specific for Asia / Oceania, as evidenced by two additional reports from China (Wu et al., 2009)  [5] and Japan [based only on E6 (Xin et al., 2001 )]. [6] However, in interpreting these results, it is necessary to take into account the observed rarity of the lines A3 and subline C. 

HPV DNA 33

The main component is oncogenes genes, which include protein components. They carry the information that can trigger tumor growth. HPV 33 DNA is formed by two helices. This enhances the properties of the virus. An important role is also given to regulatory cellular genes that regulate the basic cellular processes and transformation factors.

Life cycle HPV type 33

The life of the virus is cyclical and proceeds in several stages.

In the first stage, the virus is absorbed in the receptors of the host cell. This process is possible due to the presence of glycoproteins in the membrane complex and the virions themselves.

The second stage is characterized by the active penetration of the virus directly from the host cell structure. This triggers the basic mechanisms of interaction of the virus with the cell matrix. There are various mechanisms of interaction.

During the third stage, the virus mixes in the cell, forming vesicles in which it is under temporary protection. The endpoint of virus transport is the achievement of ribosomes and EPS. Sometimes viral particles and viruses themselves migrate to the nucleus.

The fourth stage can be described as the process of undressing the virion. The essence of this process is deproteinization and release from supercapsid and capsids.

At the fifth stage, the virion is completely dissolved, and the process of synthesis of viruses, which subsequently destroy the cell, is launched, are brought out.

At the sixth stage, the virion is collected and a nucleocapsid is formed. The self-assembly of viral particles starts.

At the seventh stage, viral particles leave the cell. Accordingly, the active stage of infection sets in, its progression.

After the life cycle is repeated, all new cells are involved, respectively, the disease develops and progresses.

Pathogenesis

HPV transmission occurs primarily through skin-to-skin contact. Epidemiological studies clearly indicate that the risk of contracting genital HPV infection and cervical cancer depends on sexual activity. HPV is very resistant to heat and drying, and asexual transmission can occur, for example, after prolonged contact with contaminated clothing  [7]. A person is more likely to be infected with HPV if he or she has had multiple sexual partners at any time, or if he is a partner of someone who has had multiple sexual partners. Sexual activity at an early age also puts a person at increased risk, like other diseases in the history of sexually transmitted infections, genital warts, abnormal Pap smears or cancer of the cervix or penis in a person or penis. Condom use may not provide adequate protection for people against HPV exposure, as HPV can be transmitted by contact with infected labia, scrotal or anal tissues that are not protected by a condom.

In addition to sexual activity, age is an important risk factor for HPV infection  [8]. The highest metaplastic activity is observed during puberty and first pregnancy and decreases after menopause. HPV infection is most common in sexually active young women aged 18 to 30 years. Prevalence sharply decreases after 30 years. However, cervical cancer is more common in women over 35 years of age, suggesting infection at a younger age and slower cancer development.

The primary immune response to HPV infection is mediated by cells; therefore, conditions that violate cell-mediated immunity, such as kidney transplantation or human viral diseases, increase the risk of acquiring and progressing HPV. [9], [10]

Local immunosuppression caused by smoking and the mutagenic activity of cigarette components has been demonstrated in cervical cells and may contribute to persistence of HPV or a malignant transformation similar to that observed in the lungs. [11],  [12] In general, if you know how transmitted HPV 33 infection can be avoided.

Symptoms

There are several forms of the disease. It is on this that the symptoms depend. With the sexual type of the disease, the mucous membranes of the genital organs and the reproductive system are damaged. There is pain, itching, burning, irritation. Often the symptoms resemble thrush: white discharge appears, sometimes curdled. Often there are warts, growths, papillomas directly on the mucous membrane of the vagina, cervical canal, and uterus.

With the skin form, growths, papillomas on the skin can appear. Mostly they are localized on the upper layer of the skin - the epidermis. They can be flat, or elevated. It is also worth noting that warts can grow quite quickly, multiply. They can be either single or multiple. Warts are often the only manifestation of this disease.

Sexually transmitted HPV infection produces one of three possible outcomes. 

1. The first is anogenital warts (condyloma acuminatum) on the genitals and anus or around them in both men and women. 
2. The second result is a latent or inactive infection, in which few people know that they are infected, since noticeable symptoms rarely occur, and the infected area remains cytologically normal. HPV DNA is present in approximately 10% of women with cytologically normal cervical epithelium. 
3. The third result is an active infection, which is associated with high-risk types of HPV, in which the virus causes changes in infected cells, which can lead to intraepithelial neoplasia of the penis, urethra, vagina, vulva or cervix. High-risk HPV types include those associated with cervical cancer and types identified as intermediate risk that are less commonly present in cancer. These infections can lead to cervical cancer. Prospective studies have shown that 15 to 28% of women who have been found to have HPV DNA have developed SIL within 2 years, compared with only 1 to 3% of women who have not been found to have HPV. 

Papillomas

It looks like a wart, or a small seal that rises on the leg. This structure is represented by connective tissue. From above it is covered with stratified epithelium. It can rise quite strongly above the surface (on the leg) on which it grows, and can also be flat and spread in the horizontal direction.

The growth rate is quite low, refers to slow-growing tumors. The danger is caused by tumors that are located on the internal organs: they can be damaged, cause bleeding. With localization in the lumen of internal organs (larynx, esophagus, intestines), they can grow and close the lumen. This causes the corresponding pathology: suffocation, obstruction. Such tumors must be removed. The main method of treating papilloma is surgical, consists in its excision.

HPV 33 in men

Quite often men are carriers of this virus, but the disease does not appear in them. The virus can persist in the blood in an inactive form, or simply suppressed by the immune system. But upon contact with a woman, her infection often occurs, since women have much lower immunity, and it does not make it possible to fully resist the infection.

The main manifestation is the formation of papillomas (plural, singular). In order to treat HPV 33 in men, medications, herbal medicine, homeopathic medicines are used. 

HPV 33 in women

Women are more likely to suffer from this virus. Moreover, they have a predominant genital form of the disease. Most often, it manifests itself in the form of papillomas and candidiasis located on the mucous membrane of the genitals. The danger is that there is the possibility of malignant degeneration of these neoplasms, their transformation into a malignant tumor. It is worth noting that often the only method of treatment is their surgical excision. But after this, additional treatment is required aimed at preventing relapse, preventing repeated neoplasms.

HPV 33 and moderate dysplasia

A distinctive feature is that they are potentially oncogenic, that is, they provoke the development of malignant neoplasms under certain conditions: reduced immunity, increased reactivity and sensitization, weakness, decreased stamina and resistance of the body, violation of the biochemical cycle, normal structural and functional state of the body, and also a violation of the hormonal background. Under such conditions, papillomas, fibromas, fibroids, fibroids, fibrotic growths develop. This is moderate dysplasia, which is directly related to HPV 33. This condition can be described as a preceding cancer. There is always a potential risk of the progression of these conditions and their transition to malignant tumors - sarcomas, cancers, leukemia.

HPV 33 and pregnancy

The appearance of HPV 33 during pregnancy is a bad sign, as this virus can lead to pregnancy pathologies. This can be either spontaneous abortion, miscarriage, or premature birth, or stillbirth. Often, children have developmental defects: physical deformities, various mental and functional abnormalities, as well as mental retardation (ZPR), mental retardation, speech defects, emotional development.

But these are extreme cases that occur with a high concentration of viruses, high viral load. Otherwise, with treatment and constant medical supervision, pregnancy can proceed normally. But there is always a risk of developing a genitourinary tract infection, bleeding, which is especially worse during childbirth. There is an increased risk of infection of the baby during childbirth.

Diagnostics

You will need an experienced virologist, or immunologist. You can also contact an infectious disease specialist, a laboratory doctor, a biochemist, a bacteriologist. If the clinic does not have such specialists, you need to contact the therapist assigned to the site, and he will refer you to the right specialist, or simply prescribe the necessary examinations. The main method of confirming the diagnosis is direct confirmation of the presence of the virus in the blood, which can be achieved only by passing the appropriate tests. Laboratory methods are used (these are the only effective and reliable research methods).

The research material in most cases is blood. Virological and serological research methods are prescribed that allow the virus to be detected in the blood, its vital products or DNA (its fragments). The laboratory uses various methods of analysis. But to detect the virus, it is worth using the PCR method, or DNA sequencing, with the help of which the viruses themselves in the blood are detected, and not antibodies as a reaction of the immune system to the introduction of the virus.

Type-specific PCR analyzes are based on sequence variations present in the E6 and E7 genes of HPV subtypes. Fourteen type-specific PCRs for high-risk HPV types (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, - 66 and - 68), which target approximately 100 bp in ORF E7. [13]

The genome contains over 100,000 nucleotides, 9 genes. On the inner surface is a matrix frame. It is formed by p17 / 18 proteins. The genome is formed by 3 structural genes and 6 regulatory. It is also worth noting that the virus is quite variable, especially when compared with other viruses. A number of researchers are still working on the decoding of HPV type 33 DNA.

The ELISA method (enzyme-linked immunosorbent assay) is not informative, because it responds to the amount of antigen-antibody complex. Moreover, antibodies persist throughout life after a single illness. Therefore, it is impossible to conclude about the stage and degree of activity of a viral infection in the body.

A doctor’s examination is also important. He will conduct a comprehensive examination, make a diagnosis. With a visual examination, the doctor will already be able to suspect the presence of HPV type 33, since it manifests itself with specific signs. But in order to finally confirm the disease, it is important not only to diagnose it, but to make a differential diagnosis. This means that the symptoms must be differentiated from other similar cases and similar manifestations.

Additional methods can serve as a microscopic examination, scraping. Depending on the severity of the pathology, an immunogram, clinical and biochemical blood and urine tests, and dysbiosis tests may be required.

Microscopy will help to directly identify the virus itself, or the products of its vital activity in a smear, to consider the features and specific characteristics under a microscope. Based on these data, it is possible to determine a clear systematic position of the pathogen, up to species and generic affiliation. The more accurately such identification is carried out, the more accurately and efficiently it will be possible to choose a treatment. It is also important to obtain quantitative indicators, since it is from the amount of virus in the blood (viral load). The plan for further treatment depends on its effectiveness.

The main method for detecting high-risk HPV is still the Pap test. This method was named after the pathologist George Papanicolaou, who introduced the method in 1949 before the cause of cervical cancer became known. Since its inception, the Pap smear has helped reduce the incidence of cervical cancer and mortality rates from about half to two-thirds. [14] A Pap test is a screening tool that looks for changes in the cells of the cervical transformation zone. Often these changes are caused by HPV.

HPV norm 33

From a biomedical point of view, the complete absence of viruses in the blood is considered the norm. But this is an ideal case, which is extremely rare in modern life. Therefore, there are certain conventional norms of HPV 33 in the body. But they are very different in different countries. There are only a few countries in which the absolute absence of the virus in the blood is considered the norm.

Treatment

Treatment consists mainly in surgical excision of neoplasms. Today, in addition to traditional surgery, there are a large number of methods for removing papillomas. So, the most effective methods are laser removal, cryotherapy, radio wave and radio frequency, electrocoagulation, thermal, electrothermal removal of papillomas. There is also the removal of papillomas with the help of chemicals.

Most HPV-induced changes in cervical cells are transient, and 90% regress spontaneously within 12–36 months as the immune system kills the virus.  [15]

Antiviral therapy is traditionally used. For example, traditional medicines are drugs such as inosiplex, interferon, amixin, cycloferone, podophyllin. Podophyllin, a cytotoxic agent that stops mitosis in metaphase (also used to treat genital warts), in combination with vidarabine, a DNA polymerase inhibitor that inhibits HPV gene expression and cell growth in cervical cancer cell lines. [16]

IFN and intravaginal 5-fluorouracil showed a variable response in clinical and in vitro studies. IFN-α is approved for the treatment of genital warts. The effects of IFN-α, IFN-β and IFN-γ in some human carcinoma cell lines were studied. [17]

It is important to carry out immunomodulating therapy aimed at normalizing the state of immunity. Immunostimulating therapy, which is based on an increase in immunity, is usually required. As a result, the immune system independently resists infection, its resistance and endurance increase, and the virus is suppressed.

For the prevention, postoperative recovery, or simply as an effective tool to reduce the number of microflora and viral load, traditional treatment is used. This may be medical therapy, various physiotherapeutic agents, alternative medicine, homeopathy and herbal medicine. Also, prophylactic antiviral vaccinations are carried out to prevent malignant degeneration of cells. When formed by candillus and papillomas, their cauterization and burning are often used.

What to do if HPV 33 is detected?

First of all, you need to see a doctor who will select the appropriate treatment. The faster treatment is started, the more effective it will be. The doctor, based on the results of laboratory and instrumental studies, will tell you what to do. If HPV 33 is detected, medical or surgical treatment (excision of papilloma) may be required. Antiviral, immunostimulating therapy is also used. 

Can HPV 33 be cured?

This pathology is well treatable in a normal state of immunity. So, if the immunity is low, various exacerbations, diseases, relapses can be observed. The danger is that the virus is potentially oncogenic. If the immunity state is normal, the virus can simply persist in the blood without causing an exacerbation of the infection.

Thus, answering the question: “Is it possible to cure HPV 33”, it is impossible to give a definite answer. So, it is important to maintain normal immunity. Avoid overwork, stress. When conducting antiviral therapy, stimulating the immune system, and vitamin therapy, you can turn the virus into an inactive state. Then it will persist in the blood without causing an acute illness. But it is practically impossible to completely eliminate the virus from the blood, a person remains a carrier of the virus, and can infect others.

Prevention HPV type 33

Prevention is based on the observance of hygiene rules, the maintenance of an adequate sexual life (having a permanent partner, protection from contacts with temporary partners, preventive treatment in the presence of an infection with a sexual partner. These are the main and main preventive measures. It is also important to maintain a normal state of immunity - periodically consult an immunologist should take tests for viruses, latent infections, drink vitamin courses and, if necessary, immunostimulating agents.

It is important to eat right, include the necessary amount of vitamin, minerals in the diet, regularly undergo preventive examinations, and if necessary, be treated promptly. Maintaining a high level of immunity is especially important, since the development of the disease is possible only with reduced immunity and impaired microflora.

Key approaches to preventing HPV infection include both risk reduction and the development of HPV vaccines. Using latex condoms and spermicide can reduce the risk of HPV infection. However, condoms are not completely reliable because HPV can be infected by contact with other parts of the body, such as the labia, scrotum, or anus, which are not protected by the condom.

A double-blind, randomized, placebo-controlled study of phase I safety and immunogenicity was performed using a subunit vaccine consisting of VLP formed from the entire major capsid protein L1 of HPV-16 strain 114K  [18]. The vaccine was obtained by inserting the L1 capsid gene into the baculovirus vector. The gene was then expressed in transfected Sf9 insect cells. The optimal dose of 50 μg of the HPV-16 VLP L1 vaccine was administered by injection into the deltoid muscle after 0, 1 and 4 months. The vaccine generated high titers of type-specific neutralizing antibodies without adjuvant and was well tolerated.

As of 2017, Gardasil 9 ® is the only HPV vaccine available in the United States. Other HPV vaccines are available outside the United States. Gardasil 9 helps prevent infection with 4 types of HPV (16, 18, 6, and 11), as well as 5 other high-risk types: 31, 33, 45, 52, and 58. Together, these types cause about 90% of cases of cervical cancer. 

American Cancer Society recommendations for the use of the HPV vaccine.

• Routine HPV vaccination for girls and boys should be started at the age of 11-12. A series of vaccinations can be started as early as 9 years old.
• HPV vaccination is also recommended for women aged 13 to 26 years and for men aged 13 to 21 years who have not yet started vaccination or have started, but have not completed the series. Men from 22 to 26 years old can also be vaccinated.
• HPV vaccination is also recommended at the age of 26 for men who have sex with men and for people with a weakened immune system (including people with HIV infection) if they have not been vaccinated before.
• For people between the ages of 22 and 26 who have not yet started vaccination or started but not completed the series, it is important to know that vaccination at an older age is less effective in reducing the risk of cancer.

Forecast

In most cases, with proper and timely treatment, the prognosis will be favorable. HPV type 33 is  quite easily eliminated, for this the main thing is to maintain normal immunity, follow all the doctor's recommendations. When papillomas appear, their surgical removal (excision) may be required. This is a quick and painless procedure that is practical and does not require recovery. Antiviral treatment plays an important role. If left untreated, complications can occur. The most dangerous is the development of malignant neoplasms.