From Human Papillomavirus To Genital Cancer

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

From human papillomavirus to genital cancer

Malignant neoplasms of the genital organs are a serious social and medical problem [1]. Penile cancer, a malignant tumor localized on the tissues of the male reproductive organ, occurs in Russia with a frequency of 0.1-7.9 per 100,000 male population, while in the structure of the incidence of malignant tumors this pathology is 0.23% [12]. This is a rather “formidable” process, in which the 3- and 5-year mortality rate of patients who did not receive treatment was 93.7% and 97.4%, respectively [14]. According to WHO estimates, penile cancer accounts for about 0.5% of all cancers in men. Cervical cancer is the second and, in some countries, the first most common malignant tumor after breast cancer, affecting young women [15]. More than 500 thousand people are diagnosed worldwide every year.new cases of cervical cancer, every 2 minutes one woman in the world dies of cervical cancer. Cancer of the vulva and vagina in Russia accounts for up to 5% of all cases of cancer of the anogenital area [13].

The territorial relationship between cancers of the cervical canal, vulva, vagina, and penis, as well as the correspondence between these types of cancers in married couples, has prompted speculation about their common etiology. It has been proven that a significant role in this is played by the defeat of the human papillomavirus (HPV). Currently, various types of HPV are classified according to their oncogenicity [15]. Thus, HPV types 16 and 18 cause 38% of all cases of penile cancer, and in basaloid and verrucous variants of cancer this figure reaches 90% [1]. About 70% of all cases of cervical cancer in the world are also caused by HPV types 16 and 18. HPV types 16 and 18 cause more than 30% of vulvar cancers and more than 50% of vaginal cancers. But you need to understand that "oncogenicity" is a relatively conditional concept. Thus, almost every tenth case of vaginal cancer and 5% of penis cancers are caused by HPV 6 and 11, which are low oncogenic [14]. Another example is the Buschke-Levenshtein tumor (Condyloma tagigantea), which is a rare but dangerous growth pattern that strongly correlates with the identification of “low risk” HPV types [4].

There is no doubt that not every person is "infected" with HPV, not every infected person has a persistent virus manifested clinically in the form of papillomas, and not every patient with genital warts eventually develops a malignant oncological process. In this regard, it can be assumed that there is a certain common "weak" link in the reactivity of the organism, the severity of which determines the further development of HPV infection. Based on modern concepts, this link is precisely the systemic and local immunity [16]. After natural infection with HPV, a low rate of seroconversion and a low level of antibodies to HPV are noted: as a rule, antibodies formed after infection with one type of pathogen do not prevent infection with other types of HPV [6]. Human papillomavirus infection can be clinically expressed, subclinical, or latent. The incubation period is on average up to 3 months. In an infected cell, the virus exists in two forms: episomal (outside the cell's chromosomes), which is considered benign, and introsomal (integrated, “embedded” in the cell's genome) - malignant. The mechanism of development of oncological diseases associated with HPV is associated with the expression of proteins E7 and E6, which inactivate the retinoblastoma protein and destroy the p53 protein, which leads, respectively, to uncontrolled cell division and the accumulation of mutations in cellular DNA [5]. Directly the virus itself is able to suppress local cellular immunity in the lesion focus and lead to a weakening of the recognition of carcinogenic cells by killer T cells [11].subclinical or latent. The incubation period is on average up to 3 months. In an infected cell, the virus exists in two forms: episomal (outside the cell's chromosomes), which is considered benign, and introsomal (integrated, “embedded” in the cell's genome) - malignant. The mechanism of development of oncological diseases associated with HPV is associated with the expression of proteins E7 and E6, which inactivate the retinoblastoma protein and destroy the p53 protein, which leads, respectively, to uncontrolled cell division and the accumulation of mutations in cellular DNA [5]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of recognition by T-killers of carcinogenic cells [11].subclinical or latent. The incubation period is on average up to 3 months. In an infected cell, the virus exists in two forms: episomal (outside the cell's chromosomes), which is considered benign, and introsomal (integrated, “embedded” in the cell's genome) - malignant. The mechanism of development of oncological diseases associated with HPV is associated with the expression of proteins E7 and E6, which inactivate the retinoblastoma protein and destroy the p53 protein, which leads, respectively, to uncontrolled cell division and the accumulation of mutations in cellular DNA [5]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of the recognition of carcinogenic cells by killer T cells [11]. In an infected cell, the virus exists in two forms: episomal (outside the cell's chromosomes), which is considered benign, and introsomal (integrated, “embedded” in the cell's genome) - malignant. The mechanism of development of oncological diseases associated with HPV is associated with the expression of proteins E7 and E6, which inactivate the retinoblastoma protein and destroy the p53 protein, which leads, respectively, to uncontrolled cell division and the accumulation of mutations in cellular DNA [5]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of the recognition of carcinogenic cells by killer T cells [11]. In an infected cell, the virus exists in two forms: episomal (outside the cell's chromosomes), which is considered benign, and introsomal (integrated, “embedded” in the cell's genome) - malignant. The mechanism of development of oncological diseases associated with HPV is associated with the expression of proteins E7 and E6, which inactivate the retinoblastoma protein and destroy the p53 protein, which leads, respectively, to uncontrolled cell division and the accumulation of mutations in cellular DNA [5]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of the recognition of carcinogenic cells by killer T cells [11]. The mechanism of development of oncological diseases associated with HPV is associated with the expression of proteins E7 and E6, which inactivate the retinoblastoma protein and destroy the p53 protein, which leads, respectively, to uncontrolled cell division and the accumulation of mutations in cellular DNA [5]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of recognition by T-killers of carcinogenic cells [11]. The mechanism of development of oncological diseases associated with HPV is associated with the expression of proteins E7 and E6, which inactivate the retinoblastoma protein and destroy the p53 protein, which leads, respectively, to uncontrolled cell division and the accumulation of mutations in cellular DNA [5]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of recognition by T-killers of carcinogenic cells [11]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of recognition by T-killers of carcinogenic cells [11]. Directly the virus itself is capable of suppressing local cellular immunity in the lesion focus and leading to a weakening of recognition by T-killers of carcinogenic cells [11].

The general relationship of HPV infection and neoplasms of the genital organs and other areas of the skin is noted, in particular, in approaches to the treatment of these nosoologies. For example, both Russian and official recommendations of many other countries for the treatment of diseases associated with HPV infection include the drug imichimod. The drug imiquimod is widely used in the world due to its ease of use, effectiveness, and the possibility of combination with other means of treatment of complicated HPV diseases. Interestingly, imiquimod has been tested in the treatment of various malignant neoplasms of the skin - squamous cell carcinoma, basal cell carcinoma, melanoma cancer, as well as precancerous neoprocesses - keratoses [7, 8, 9].

If we turn to the authoritative database of medical and biological publications created by the US National Center for Biotechnology Information Pubmed, then there are about 3200 publications on the use of the drug "imiquimod" alone, while in the light of cancer treatment, the number of scientific papers "cancer + imiquimod" exceeds 1500 [ten]. This confirms the possible general mechanisms of suppression by imiquimod of both the papillomavirus infection itself and the malignant neoplasms associated with it.

The effectiveness of the antiviral and antitumor action of imichimod is due to its ability to interact with plasma cells, which are the main producers of IFN type 1, in particular IFNα. At the same time, type 1 IFNs activate the production of a cascade of proinflammatory cytokines, such as TNF-α, IL-1β, IL-5, -6, -8, -12. The antitumor effect of imiquimod is also manifested by the suppression of tumor growth by capillaries. Also, an important property of imiquimod in the treatment of HPV and tumors is its proapoptotic effect associated with the recruitment of an intracellular protein factor - a regulator of apoptosis Bcl-2 and an increase in the expression of Bcl-2 and Bcl-xL, initiating cell death. In the mechanism of antiviral and antitumor action, the decisive role is played by the ability of imichimod to promote the infiltration of tissue lesions by immunocompetent cells [6].

Thus, at present there is an effective topical drug that can not only help treat the clinical manifestations of HPV and reduce the persistence of the virus in the body, but also affect the development of pathological processes underlying carcinogenesis associated with human papillomavirus infection.

Literature sources

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3. Ornellas AA, Seixas AL, Marota A, et al. Surgical treatment of invasive squamous Cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol 1994; 151 (5): 1244-1249.1
4. Yanofsky VR, Patel RV, Goldenberg G: Genital warts: a comprehensive review. J Clin Aesthet Dermatol 2012; 5: 25-36.
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6. Schön MP, Bong AB, Drewniok C. Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J. nat. Cancer 2003; 95 (15): 1138-1149.
7. Siegel JA Korgavkar K., Weinstock MA Current perspective on actinic keratosis: a review. Brit. J. Dermatol. 2016: doi: 10.1111 / bjd.14852.
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10. Database of medical and biological publications - Pubmed.

11. Fayzullina E. V. Clinical and organizational aspects of medical care for patients with anogenital warts as the most important factor in preserving the reproductive health of the population.

    Faizullina, D. V. Frizin, L. K. Bunakova // Practical medicine. - 2012 - № 9 (65). - S. 170-174.

12. Grandolfo M and Milani M. Efficacy and tolerability of polyphenon E in “difficult-to-treat” multiple genital warts in an HIV-positive male subject. Case Rep Dermatol 2017; 9: 5-59.
13. Werner RN, Westfechtel L, Dressler C, et al. Anogenital warts and other HPV-associated anogenital lesions in the HIV-positive patient: a systematic review and metaanalysis of the efficacy and safety of interventions assessed in controlled clinical trials. Sex Transm Infect 2017; 93: 543-550
14. Smith KJ, Skelton HG, Yeager J, et al. Increased drug reactions in HIV-1-positive patients: a possible explanation based on patterns of immune dysregulation seen in HIV-1 disease. Clin Exp Dermatol 1997; 22: 118-123.
15. Godley MJ, Bradbeer CS, Gellan M, et al. Cryotherapy compared with trichloracetic acid in treating genital warts. Genitourin Med 1987; 63: 390-2 /

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