Papillomatosis as a state of impaired immune status

Etiology and pathogenesis of papillomavirus

Human papillomaviruses belong to genus A of the Papovaviridae family, have a diameter of 55 nm, without an envelope, contain DNA that replicates in the nuclei of squamous epithelial cells, up to 88% of the weight of the virion is made up of structural proteins. HPVs are species-specific and tissue-specific viruses; more than 100 serotypes are known with numerical designations in the chronological order of their discovery. Each serotype has its own epidemiological characteristics and degree of cancer risk, which is encoded by special oncoproteins. They induce proliferation of keratinocytes, disrupt apoptosis and cause malignant transformation of epithelial cells, proliferation, impaired keratinization and atypia.

The target organs of the virus are primarily the skin and mucous membranes of the anourogenital area and upper respiratory tract, as well as the oral cavity, esophagus, rectum, and conjunctiva of the eye.

HPV types:

1 – plantar warts;

2 – vulgar warts of the hand and mosaic type of plantar warts;

3 – flat warts, verrucous epidermodysplasia;

4, 7 – palmoplantar warts of the hyperkeratotic type, butcher’s papillomas;

5, 10 – flat warts, spotty lesions of epidermodysplasia verruciformis (degenerate into malignant);

6, 11 – genital warts, laryngeal papillomas;

8, 9, 12 – warty epidermodysplasia (degenerates into malignant);

13 – limited hyperplasia of the oral cavity;

14, 15 – verrucous epidermodysplasia;

16, 18 – Bowen papulosis of the genital organs, cervical cancer (the highest degree of malignancy).

HPV infection occurs after contact with a sick person or a virus carrier. For example, in a swimming pool, sauna, gym; through products (from people who process meat, fish, poultry); self-infection through shaving, hair removal, scratching, nail biting; during sexual intercourse; during childbirth from mother to child. The incubation period ranges from 3 weeks to 9 months. The virus can remain inactive for a long time, waiting for the body's defenses to decrease, after which viral DNA replicates in the nuclei of squamous epithelial cells and causes hyper- and parakeratosis.

Morphologically, the cells of the upper sections of the spinous and granular layers are vacuolated, do not contain keratohyalin granules, their nuclei are surrounded by a light rim (koilocytes) - these are destructive epithelial cells with a sharply altered metabolism. Then the contents of the cell are released into the intercellular space with viral particles, and they enter the macrophages, dermis, and blood vessels.

Further, everything depends on the correct immune response: the tissue macrophage absorbs the pathogen and presents antigenic peptides to T and B cells, initiating the development of a cellular and humoral immune response. In this case, the macrophage releases cytokines that activate nonspecific resistance factors: neutrophils, monocytes/macrophages, NK cells; also act on T-, B-lymphocytes, including a specific immune response. Own interferons are capable of inhibiting the intracellular reproduction of viruses.

Features of the immune status affect the prevalence of HPV, and the disease can take on a systemic nature. Therefore, children are more likely to suffer from vulgar and juvenile warts. Acute condylomas in most cases occur between the ages of 16–30 years. To identify the type of virus, DNA hybridization and polymerase chain reaction (PCR) are used. Accurate determination of the type of virus is of utmost importance for predicting the development of neoplastic processes. And an immunogram is an analysis to predict the systemic nature of the process.

CLINICAL MANIFESTATIONS OF HPV

Common (vulgar warts) account for 71% of all skin warts and are often found in school-age children. Dermatoscopically, these are round papules with a diameter of 1–10 mm, with an uneven surface, hyperkeratosis, flesh-colored or yellow-brown in color, with a pronounced vascular pattern in the form of black-brown dots (thrombosted capillaries). Localized on the hands, fingers, shoulders, forearms, face, red border of the lips and oral mucosa.

Flat, or juvenile, warts account for 4% of all skin warts. Dermoscopically, these are flat papules, pigmentless, clearly separated, with a smooth surface, 1–5 mm in diameter, rising 1–2 mm above the skin level. The shape can be round, polygonal, oval, linear, and can be grouped. Color – light brown, pink. Localized on the face, dorsum of the hands, legs, oral mucosa, and genitals.

Plantar warts account for 34% of all warts. Dermatoscopically, these are hard hyperkeratotic growths with a rough, uneven surface and visible black-brown dots (thrombosed capillaries), the skin pattern is twisted. They are localized on the soles in the projection of the heads of the metatarsal bones, the heel, and the pads of the toes. Very painful when walking.

Filiform warts (acrochords) occur in 50% of the population over 50 years of age and are localized on the neck, in the axillary and groin areas, under the mammary glands. Dermoscopically, these are light, oblong formations, soft consistency, with hairy, fringe-like processes. Acrochords more often develop in women during menopause and are considered as manifestations of skin aging. In young women, the formation of acrochords is associated with impaired ovarian activity and infantilism.

Epidermodysplasia verruciformis (Lewandowski-Lutz epidermodysplasia verruciformis) is a generalized HPV viral infection characterized by rashes of flat warts of light brown or pink color, which can merge into large plaques, on the hands and feet, sometimes on the body - in a flatter form. This is genodermatosis, but in 30% of people aged 30–40 years it can degenerate into malignant formations in areas of insolation. The most oncogenic are HPV 5, 8, 14. Possible development of Bowen's disease, squamous cell carcinoma, bowenoid papules.

Anourogenital warts (genital warts) are highly contagious. This disease is benign, but cases of malignancy are known. There are several clinical and morphological types: papillary varieties of papillomas with exophytic growth, flat condylomas, giant Buschke-Levenshtein condyloma. They occur at the site of injury during sexual intercourse. Dermoscopically, they have a pronounced papillary surface, with exudate between the papillae, hyperemic, with a pronounced vascular pattern, shiny and macerated, reaching 1.5 cm. With immunosuppression, they tend to merge. They are localized on the mucous membrane of the vulva, labia majora and minora, clitoris, in the perianal area, in the perineum in women, on the foreskin in men. Giant Buschke-Levenshtein condyloma is a rare lesion on the penis. It manifests itself as warty growths, with vegetations and hyperkeratosis, with small elements along the periphery. It is possible to develop Bowen's disease, squamous cell carcinoma, Bowenoid papules, and squamous cell carcinoma of the penis.

Dermoscopic examination

When examining a patient with HPV infection, dermatoscopy, PCR diagnostics with determination of the type of virus are used (16, 18, 31, 33), sometimes histological examination, cytology, colposcopy, meatoscopy, bacterioscopy of urinary tract discharge, and enzyme-linked immunosorbent assay of blood serum. Differential diagnostics and immunogram are required. In the immunogram, the state of cellular and humoral immunity is important.

Treatment

Treatment of HPV infection is aimed at destruction of formations, correction of general and local immune status. But even with the right approach, the relapse rate is 25–30%, regardless of the method of their destruction.

Treatment tactics are determined by many factors: the initial state of immunity, the presence of concomitant diseases, the localization of the process, the nature of the urogenital infection, the pathological process of the cervix, the use of previous antiviral therapy.

Electrosurgical methods, radio wave therapy, laser therapy (neodymium, CO2 laser, diode), cryotherapy, and chemical destructors are used as destruction. The most popular are liquid nitrogen destruction and laser and radio wave destruction, since the virus is lysed and killed, and the relapse rate is 10–20%. With electrical destruction, the relapse rate reaches 60–95%.

Antiviral treatment options are varied, but all of them are aimed at immunomodulation, inducing interferon production, and antiviral action. These are mainly “Laferon” (1–3 million units, 2–3 times a week IM), “Cycloferon” (3 times a week IM), “Liasten” (2 times a week IM) . The main clinical effect of Cycloferon is associated with the induction of early alpha interferon. When applied externally, the main cells producing interferon, after the administration of Cycloferon liniment, are epithelial cells and lymphoid elements of the mucous membrane. Depending on the type of infection, the activity of one or another part of the immune system predominates. "Cycloferon" activates T-lymphocytes and natural killer cells, normalizes the balance between subpopulations of T-helpers and T-suppressors. The drug increases the biosynthesis of functionally complete antibodies (high-avidity), facilitating more effective therapy, and normalizes cellular immunity. The anti-inflammatory activity of the drug is ensured by enhancing the functional activity of neutrophils and activating phagocytosis.

***

In conclusion, I would like to say that infections caused by human papillomavirus are very common, contagious, and some types of HPV can lead to malignant neoplasms. Immune status determines the prevalence of the virus, and also changes its indicators with active reproduction of HPV.

First published: Les Nouvelles Esthetiques 2016/№2(96)