Anogenital (venereal) warts: clinical guidelines

List of Abbreviations

HIV - human immunodeficiency virus

HPV — human papillomavirus

DNA - deoxyribonucleic acid

STI — sexually transmitted infection

ICD — International Classification of Diseases

PCR — polymerase chain reaction

CIN - cervical intraepithelial neoplasia

VIN - vulvovaginal intraepithelial neoplasia

PIN - penile intraepithelial neoplasia

AIN - anal intraepithelial neoplasia

** - drug is included in the VED list

Terms and Definitions

Anogenital (venereal) warts are a viral disease transmitted predominantly sexually, caused by the human papillomavirus.

Human papillomavirus (HPV) is an anthroponotic DNA-containing virus belonging to the genus Papillomavirus of the family Papillomaviridae, which includes more than 100 species from 53 genera and about 200 types.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Anogenital (venereal) warts are a viral disease transmitted predominantly sexually, caused by the human papillomavirus (HPV) and characterized by the appearance of exophytic and endophytic growths on the skin and mucous membranes of the external genitalia, urethra, vagina, cervix, perianal region, anal canal, and oropharynx.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The causative agent of the disease, human papillomavirus, belongs to the genus of papillomaviruses (Papillomaviridae) of the family Papovaviridae (Papovaviridae), consisting of 16 genera, representatives of 5 of which are pathogenic to humans.

The International Agency for Research on Cancer has recognized HPV as the etiological agent of a wide range of oncological diseases, such as cancer of the cervix, vulva, vagina, anal canal, penis, head and neck, esophagus, as well as anogenital (venereal) warts and recurrent respiratory papillomatosis [1].

Currently, more than 200 genotypes of human papillomaviruses have been identified, of which about 45 HPV genotypes can infect the urogenital tract.

HPV is a highly contagious mucosotropic and dermatotropic virus transmitted from person to person through oral, genital, and anal sexual contact, as well as through contact-household and vertical routes.

HPV infection occurs with any form of sexual contact, close household contact, and infection of children is also possible at birth through the natural birth canal. The possibility of self-infection (autoinoculation) and transmission of HPV via household items remains insufficiently studied. Infection is facilitated by the presence of microtrauma and inflammatory processes of the skin and mucous membranes, leading to a decrease in local immunity, as well as the resistance of HPV to antiseptics [113]. Medical personnel can become infected with HPV in case of violation of sanitary prevention rules during laser, radiowave, or electrosurgical destruction of anogenital (venereal) warts by inhaling the resulting smoke containing viral particles. The incubation period of the disease can last from several months to several years. The average time between HPV infection and the development of anogenital (venereal) warts ranges from 3 months in women to 11 months in men. Human infection can occur with one or multiple HPV types [2].

During the infection process, HPV penetrates via endocytosis into immature metaplastic cells, most commonly of the basal layer, and is transported to the cell nucleus. In the cells of the epithelial basal layer, the viral DNA can persist for a long time as an extranuclear plasmid in a silent state (episomal form) and be detected by molecular biological methods in the absence of clinical and cytological changes. As epithelial cells differentiate and mature, active viral replication (productive stage) or integration of HPV DNA into the genome of the infected cell (integrative stage) is possible. In a productive infection, transcription of late genes, synthesis of capsid proteins, and virus assembly take place, followed by the release of its progeny particles. The HPV life cycle ends in mature cells of the stratified epithelium, and virions are released with desquamated cells.

With adequate immune resistance of the body, spontaneous elimination of HPV occurs in 90% of infected individuals within 2 years [108, 109]. Exposure to adverse exogenous and endogenous factors can lead to increased viral replication, with the process transitioning from the episomal (latent) stage to the stage of productive or integrative infection, during which clinical manifestations of the disease develop - anogenital (venereal) warts or HPV-induced cytological changes (intraepithelial neoplasias of various grades: cervical (CIN), vulvar (VIN), penile (PIN), anal (AIN), and of other organs).

Up to 90% of all cases of anogenital (venereal) warts in men and women are caused by HPV genotypes 6 and 11. High-risk oncogenic HPV is detected in 20–50% of patients with anogenital (venereal) warts. High-risk oncogenic HPV (e.g., types 16 and 18) causes the majority of precancerous conditions and cancers of the cervix, penis, vulva, vagina, anus, and oropharynx [3], whereas HPV types 6 and 11 cause anogenital (venereal) warts and recurrent respiratory papillomatosis, as well as papillomatosis of the conjunctiva, nose, oral cavity, and larynx.

HPV infection is frequently asymptomatic or goes unrecognized [4-6].

1.3 Epidemiology of the Disease or Condition

The incidence of anogenital (venereal) warts in men and women (including new cases and relapses) ranges from 160 to 289 cases per 100,000 population, with a mean value of 194.5 cases per 100,000 population, while the average annual detection rate of new cases of anogenital (venereal) warts is 137 cases per 100,000 population among men and 120.5 cases per 100,000 population among women [7]. Prior to the introduction of HPV vaccination, approximately 355,000 new cases of anogenital (venereal) warts were detected worldwide each year [8-9].

In the Russian Federation, the incidence of anogenital (venereal) warts in 2022 was 17 cases per 100,000 population. However, these figures do not reflect the true incidence rate and are a consequence of incomplete registration of new cases [10].

1.4 Features of Coding the Disease or Condition

A63.0 - Anogenital (venereal) warts

1.5 Classification of the disease or condition

Several clinical variants of anogenital (venereal) warts are distinguished:

- condylomata acuminata;

- papular warts;

- macules / patch lesions;

- Buschke-Löwenstein giant condyloma.

1.6 Clinical presentation of the disease or condition

Condylomata acuminata are small, soft growths in the form of delicate papillae or cockscombs with a typical "mottled" and/or loop-like pattern, localized in the area of the inner leaflet of the prepuce, glans penis, external urethral meatus, labia minora, vaginal vestibule, vagina, cervix, inguinal region, perineum, and anal area. The color of the condylomas can be skin-toned, intensely red, or snow-white (upon maceration).

Papular warts are papular eruptions without finger-like projections, localized on the keratinized epithelium of the outer leaflet of the prepuce, the body of the penis, the scrotum, the lateral area of the vulva, the pubis, the perineum, and the perianal region.

Patch lesions are grayish-white, pinkish-red, or reddish-brown spots on the skin and/or mucous membrane of the genitalia.

Buschke-Löwenstein giant condyloma are papillomas that coalesce to form a lesion with a wide base, covered with villous proliferations, divided by pronounced grooves on the labia majora and minora, extending to the femorolingual (femoro-inguinal) folds and the anal region. Isolated condylomata acuminata are present at the periphery of the formation. Over time, the formations grow larger, become covered with scales of keratinized epithelium, and undergo maceration. Discharge accumulates in the grooves running between them, and infection frequently occurs, as a result of which the discharge acquires a purulent character and an unpleasant odor.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria

The diagnosis of anogenital (venereal) warts is established based on clinical manifestations.

2.1 Complaints and Anamnesis

The presence of single or multiple exophytic growths in the form of papules, papillomas, or spots on the skin and mucous membranes of the genitalia, perianal region, perineum, anus, and inguinal folds; moderate pruritus and paresthesias in the affected area may occur; pain during sexual intercourse (dyspareunia); when eruptions are localized in the urethral area, pruritus, burning, and painful urination (dysuria) occur; with extensive urethral lesions, difficult urination and hematospermia (blood in the semen) occur; painful fissures and bleeding of the skin and mucous membranes at the sites of the lesions.

Anogenital (venereal) warts on the anal mucosa are observed predominantly in individuals with a history of anal intercourse; however, they may also occur in men and women with no such history [8].

Children with anogenital (venereal) warts are at risk of autoinoculation and the spread of infection to healthy skin areas. Any child presenting with anogenital (venereal) warts should be evaluated for a history of sexual contact, although the majority of children acquire the infection through non-sexual routes.

2.2 Physical Examination

For objective clinical manifestations of the disease identified during physical examination, see the "Clinical Presentation" section.

2.3 Laboratory Diagnostics

Comments:

To obtain reliable laboratory results, a number of requirements must be met, including:

- collection of clinical material from the urethra no earlier than 3 hours after the last urination; in the presence of profuse urethral discharge, 15-20 minutes after urination;

- collection of clinical material from the cervical canal and vagina before menstruation or 2 days after its cessation;

- collection of clinical material from the cervical canal and vagina no earlier than 24-48 hours after transvaginal ultrasound examination and colposcopy;

- exclusion of vaginal douching on the eve of and on the day of the examination;

- exclusion of genital hygiene procedures using intimate hygiene products on the day of the examination;

- exclusion of the use of fat-containing vaginal medicinal products (suppositories, creams, vaginal tablets) for 3-5 days prior to the examination.

Comments:

Biopsy is also indicated for immunocompromised patients (including HIV-infected individuals) whose lesions do not respond to standard therapy or whose clinical presentation worsens during treatment [12-14].

- laboratory tests for other STIs: syphilis (detection of antibodies to Treponema pallidum in non-treponemal tests (RPR, VDRL) (qualitative and semi-quantitative test) in blood serum and/or detection of antibodies to Treponema pallidum by enzyme immunoassay (EIA) in blood), gonococcal infection, chlamydial infection, urogenital trichomoniasis;

- detection of classes M, G antibodies (IgM, IgG) to human immunodeficiency virus HIV-1 in the blood. Detection of classes M, G antibodies (IgM, IgG) to human immunodeficiency virus HIV-2 in the blood;

- determination of hepatitis B virus surface antigen (HBsAg) in the blood;

- detection of total classes M and G antibodies (anti-hCV IgG and anti-hCV IgM) to hepatitis C virus in the blood [7, 15-19].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

2.4 Instrumental Diagnostics

2.5 Other Procedures

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Destruction or surgical excision methods lead to the removal of anogenital (venereal) warts, but none of these methods completely eliminates the risk of recurrence, as the removal of lesions does not lead to the elimination of the HPV that caused their development.

Since no single treatment method is universal, combination therapy may be used.

Detection of HPV associated with anogenital (venereal) warts in the absence of clinical manifestations of the disease is not an indication for any treatment.

3.1. Conservative management

imiquimod, 5% topical cream, applied in a thin layer to genital warts 1 time per day before bedtime (for 6–10 hours) 3 times a week (every other day). In the morning, the cream is washed off the skin with warm water and soap. Course treatment (no more than 16 weeks) is continued until the disappearance of anogenital (venereal) warts [22-26]

Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)

Comments:

The use of an excessive amount or prolonged contact of the medicinal product with the skin may cause a pronounced local reaction in the form of redness, irritation, induration, erosions, vesicles, or hypopigmentation [27].

Contact of the medicinal product with mucous membranes should be avoided.

When treating anogenital (venereal) warts located under the foreskin, it is necessary to wash the affected area daily by retracting the foreskin; if early signs of phimosis are detected, treatment must be stopped immediately.

If the local reaction to the application of the drug causes discomfort, a break in treatment for a few days is possible.

The medicinal product is not used on skin areas with open ulcers or wounds after other types of medical or surgical treatment until the skin has healed.

Before sexual contact, the cream must be washed off the skin.

Use during pregnancy is possible under strict indications, although preclinical data indicate a low risk of teratogenicity [28].

When used during lactation, breastfeeding must be discontinued.

The drug is contraindicated in individuals under 18 years of age.

electrocoagulation [7, 15, 18, 29-35]

For adults — strength of recommendation B (level of evidence — 2)

For children — strength of recommendation C (level of evidence — 5)

or

CO2 laser vaporization [7, 15, 18, 36-38]

For adults — strength of recommendation B (level of evidence — 2)

For children — strength of recommendation C (level of evidence — 5)

or

radiofrequency thermoablation [15, 32, 33, 39-41]

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

or

cryodestruction [29, 31-33, 42, 99]

GCR BLEL 2Grade of Recommendation B (Level of Evidence - 2)

For children — Strength of recommendation C (level of evidence — 4)

For adults — strength of recommendation B (level of evidence — 2)

Comments:

The therapeutic procedure is performed under local anesthesia.

Comments: Preparations containing interferon alfa-2b** [45, 47, 48] or recombinant human interferon gamma** [11, 102] are used according to the instructions for use. Inosine pranobex [47, 59, 60, 117], Solanum tuberosum shoot polysaccharides [61, 64, 106, 107] or potato shoot polysaccharide fraction [61, 63-67, 106], and local antiseptics and disinfectants [49-52] may also be used according to the instructions for use.

3.2. Surgical treatment

The indication for surgical excision of anogenital (venereal) warts is the failure of conservative and destructive treatments, and suspected malignancy. It is inappropriate to postpone radical treatment due to the risk of malignant transformation. Surgical excision of anogenital (venereal) warts is performed by various methods: sharp dissection, electrosurgical or radiosurgical device, or surgical CO2 laser. The surgery is performed under topical or infiltrative skin anesthesia; for a large affected area in the anogenital region or in the presence of condylomas in the anal canal, spinal anesthesia is used. The recurrence rate of anogenital (venereal) warts ranges between 17-29% [74].

Comments:

In patients with Buschke-Löwenstein tumor, involved tissues must be excised with a margin of at least 0.5 cm from the base of the lesion. This frequently results in large defects requiring plastic surgical techniques (V-Y skin plasty, use of free grafts) [75].

3.3. Other treatment

Diet therapy is not used.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

In most cases, rehabilitation is not required after the removal of anogenital (venereal) warts.

Rehabilitation is indicated following surgical intervention for the removal of anogenital (venereal) warts involving the anorectal region or urethra.

The need for rehabilitation of patients who have undergone surgical treatment for anogenital (venereal) warts of the perianal area and anal canal is due to surgical trauma in these regions. The presence of postoperative wounds in these anatomical areas, especially with a large lesion area, and their healing by secondary intention, create a risk of pyoseptic complications. Pain of varying severity and potential impairment of defecation and urination in the postoperative period can lead to significant social maladaptation and reduce the quality of life in this category of patients.

Special attention should be paid to patients who have undergone surgery on the anal canal and extensive plastic surgery on the perianal area, as anal continence function may be impaired in these cases.

Removal of anogenital (venereal) warts of the urethra may be accompanied by the long-term development of urethral stricture.

Stage 1 – early rehabilitation, from days 4–6 to days 7–10 after surgery. During this period, the patient undergoes inpatient rehabilitation for 3–5 days, after which further rehabilitation continues on an outpatient basis for 7–14 days.

The most important objectives of the first stage of rehabilitation are the normalization of gastrointestinal function with the establishment of normal stool consistency and frequency. In addition, this stage involves monitoring hemostasis and the wound process, as well as managing postoperative pain.

Stage 2 – from day 15 to day 45 after surgery, aimed at accelerating reparative processes, wound healing, and monitoring gastrointestinal tract function.

The criterion for completion of rehabilitation is complete healing of postoperative wounds of the perineum, anal canal, and urethra.

5. Prevention and Dispensary Observation

– informing the population about the transmission routes of HPV and its consequences;

– avoiding casual sexual contacts;

– using barrier methods of contraception during all types of sexual contact;

– screening for anogenital (venereal) warts in sexual partners of patients with anogenital (venereal) wart lesions [15].

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

Comments:

For the prevention of HPV-associated diseases, the following vaccines are registered in the Russian Federation: recombinant adsorbed human papillomavirus vaccine containing the AS04 adjuvant (bivalent, containing HPV types 16 and 18 antigens) and quadrivalent recombinant human papillomavirus vaccine (types 6, 11, 16, 18) (containing HPV types 6, 11, 16, 18 antigens). The vaccines are approved for use from 9 years of age, are strictly prophylactic, have no therapeutic effect, and do not protect against all high-risk HPV types, although they exhibit cross-protection against certain high-risk HPV genotypes (31, 33, 45). Vaccination is recommended before the onset of sexual activity. Among HPV-uninfected individuals, the quadrivalent recombinant HPV vaccine provides nearly 100% protection against anogenital (venereal) warts associated with HPV types 6 and 11, and approximately 83% protection against all anogenital (venereal) warts.

The recommended vaccination course consists of 3 doses administered according to the schedule (0–2–6 months): the first dose on the scheduled date; the second dose 2 months after the first; the third dose 6 months after the first. An accelerated vaccination schedule is permitted, in which the second dose is administered 1 month after the first injection, and the third dose 3 months after the second injection. The vaccination course is considered completed even if the interval between injections is violated, provided all three injections are administered within 1 year. An alternative 2-dose vaccination schedule (0–6 months) with the preparation is permitted in individuals aged 9–13 years. In this case, if the second dose is administered earlier than 6 months after the first dose, a third dose must always be given.

6. Organization of Medical Care

Treatment is primarily carried out on an outpatient basis in a dermatovenereological medical organization; when anogenital (venereal) warts are localized on the rectal mucosa, treatment is performed in a coloproctological medical organization; when women, including pregnant women, present with anogenital (venereal) warts with extensive lesions on the cervical mucosa, treatment is provided in an obstetric and gynecological medical organization; for intraurethral localization of anogenital (venereal) warts, treatment is conducted in a urological medical organization.

Indications for hospital admission to a medical organization:

lesions of the skin and mucous membranes for the purpose of surgical excision and subsequent pathomorphological examination of the surgical material.

When a patient with clinical manifestations of anogenital (venereal) warts is identified by dermatovenereologists, obstetrician-gynecologists, coloproctologists, urologists, or physicians of other specialties, form No. 089-u/kv «Notification of a patient with a newly established diagnosis of syphilis, gonococcal infection, chlamydial infections, trichomoniasis, anogenital herpesviral infection, anogenital (venereal) warts, mycosis, scabies» is filled out in the manner prescribed by the letter of the Russian Ministry of Health dated March 2, 2015, No. 13-2/25.

7. Additional Information

The prognosis for life is favorable in the absence of evidence of cellular atypia in anogenital (venereal) warts. However, recurrences after destruction are observed in 20–30% of patients. For adolescents, abstinence from sexual activity is the most reliable method for preventing HPV infection [115].

The risk of HPV infection is reduced by the correct use of condoms before the initiation of sexual contact and by limiting the number of sexual partners; although these measures cannot completely protect against HPV infection, they can reduce the transmission of HPV to a sexual partner. The following factors negatively affect treatment outcomes and increase the risk of HPV infection:

1. a large number of sexual partners (more than 3 during the past year, more than 6 over a lifetime [93, 94];

2. anal sexual contact, especially in men who have sex with men [95];

3. concomitant sexually transmitted infections, particularly those caused by herpes simplex virus type 2, cytomegalovirus, Chlamydia, and genital mycoplasmas [96];

4. immunodeficiency states, especially HIV-induced immunodeficiency [97];

5. tobacco smoking, as cigarette combustion products concentrate on mucous membranes, including the cervix, leading to suppression of the immune activity of Langerhans cells [98];

6. failure to observe personal hygiene rules by individuals of either sex and violation of sanitary standards by medical personnel.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Alexey Alexeevich Kubanov - Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Director of the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, President of the Russian Society of Dermatovenereologists and Cosmetologists.

2. Yuri Anatolyevich Shelygin - Academician of the Russian Academy of Sciences, Scientific Director of the Ryzhikh National Medical Research Center of Coloproctology of the Russian Ministry of Health, President of the Association of Coloproctologists of Russia.

3. Margarita Rafikovna Rakhmatulina - Doctor of Medical Sciences, Professor, Deputy Director for Organizational and Analytical Work at the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Chair of the Executive Committee of the Russian Society of Dermatovenereologists and Cosmetologists.

4. Inna Anatolyevna Apolikhina - Doctor of Medical Sciences, Professor, Head of the Department of Aesthetic Gynecology and Rehabilitation at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.

5. Nika Dzhumberovich Akhvlediani - Doctor of Medical Sciences, Professor at the Department of Urology, Yevdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health, Member of the Russian Society of Urologists.

6. Natalia Viktorovna Bolshenko - Candidate of Medical Sciences, Senior Researcher at the Central Research Institute of Epidemiology of Rospotrebnadzor, Member of the Russian Society of Dermatovenereologists and Cosmetologists.

7. Alexey Viktorovich Veselov - Candidate of Medical Sciences, Executive Secretary of the Association of Coloproctologists of Russia.

8. Mikhail Alexandrovich Gomberg - Doctor of Medical Sciences, Professor, Chief Researcher at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow Healthcare Department, Member of the National Alliance of Dermatovenereologists and Cosmetologists Union.

9. Elena Alexeevna Gorbunova - Obstetrician-Gynecologist, Researcher at the Department of Aesthetic Gynecology and Rehabilitation, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.

10. Natalia Vitalievna Dolgushina - Doctor of Medical Sciences, Professor, Deputy Director for Research at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.

11. Georgy Leonidovich Katunin - Candidate of Medical Sciences, Dermatovenereologist at the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Member of the Russian Society of Dermatovenereologists and Cosmetologists.

12. Kostarev Ivan Vasilievich - Doctor of Medical Sciences, Head of the Department of Minimally Invasive Coloproctology, National Medical Research Center for Coloproctology named after A.N. Ryzhikh of the Russian Ministry of Health, member of the Association of Coloproctologists of Russia.

13. Moskalev Alexey Igorevich - Candidate of Medical Sciences, Head of the Scientific and Educational Department, Physician at the Department of Colonic Oncology and Surgery, National Medical Research Center for Coloproctology named after A.N. Ryzhikh of the Russian Ministry of Health, member of the Association of Coloproctologists of Russia.

14. Mudrov Andrey Anatolyevich - Candidate of Medical Sciences, Researcher at the Department of General and Reconstructive Coloproctology, National Medical Research Center for Coloproctology named after A.N. Ryzhikh of the Russian Ministry of Health, member of the Association of Coloproctologists of Russia, member of the Association of Coloproctologists of Russia.

15. Nechaeva Irina Anatolyevna - Candidate of Medical Sciences, Dermatovenerologist, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.

16. Nekhrikova Svetlana Viktorovna - Candidate of Medical Sciences, Coloproctologist at the Department of General and Reconstructive Coloproctology, National Medical Research Center for Coloproctology named after A.N. Ryzhikh of the Russian Ministry of Health, member of the Association of Coloproctologists of Russia.

17. Perlamutrov Yury Nikolaevich - Doctor of Medical Sciences, Professor, Head of the Department of Skin and Venereal Diseases, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.

18. Plakhova Ksenia Ilyinichna - Doctor of Medical Sciences, Scientific Secretary, Acting Head of the STI Department, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.

19. Potekaev Nikolay Nikolaevich - Doctor of Medical Sciences, Professor, Director of the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow Healthcare Department, Chief freelance specialist in dermatovenereology and cosmetology of the Russian Ministry of Health, President of the National Alliance of Dermatovenerologists and Cosmetologists Union.

20. Priputnevich Tatyana Valeryevna - Corresponding Member of the RAS, Doctor of Medical Sciences, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health.

21. Titov Alexander Yuryevich - Doctor of Medical Sciences, Scientific Secretary, National Medical Research Center for Coloproctology named after A.N. Ryzhikh of the Russian Ministry of Health, member of the Association of Coloproctologists of Russia.

22. Uvarova Elena Vitalievna - Corresponding Member of the RAS, Doctor of Medical Sciences, Professor, Head of the 2nd Gynecological Department, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists.

23. Frolov Sergey Alekseevich - Doctor of Medical Sciences, Deputy Director for Research, National Medical Research Center for Coloproctology named after A.N. Ryzhikh of the Russian Ministry of Health, member of the Association of Coloproctologists of Russia.

24. Chikin Vadim Viktorovich - Doctor of Medical Sciences, Senior Researcher at the Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.

Conflict of interest:

The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

• Specialists: dermatovenerologists, obstetrician-gynecologists, coloproctologists, urologists, pediatricians, infectious disease specialists.

• Residents and trainees of continuing professional education programs in the specified specialty.

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)

Table 3. Rating scale for levels of recommendation evidence (LRE) for prevention, diagnostic, treatment and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The guideline update mechanism provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

none

Appendix B. Physician Action Algorithms

Flowchart 1. Patient management algorithm

Appendix C. Patient Information

1. Anogenital (venereal) warts are an infectious disease caused by the human papillomavirus, which is sexually transmitted.

2. For the prevention of human papillomavirus infection, it is necessary to:

   - correct use of condoms or abstaining from all forms of casual sexual contact (oral, vaginal, anal);

   - abstaining from any forms of sexual contact with individuals who have symptoms of sexually transmitted infections (genital discharge with an unpleasant odor and color, rashes or ulcerations on the external genitalia).

3. During treatment and follow-up, sexual contact must be avoided.

4. Transmission of the human papillomavirus can occur in the absence of clinical manifestations of the disease.

5. Consistent and correct use of condoms helps reduce the risk of infecting a sexual partner.

6. Screening for other sexually transmitted infections, HIV infection, and hepatitis B and C is recommended.

7. The indication for the treatment of anogenital (venereal) warts is the presence of clinical manifestations of the disease. Detection of HPV in the absence of clinical manifestations is not an indication for prescribing therapy.

8. None of the therapy methods has a proven advantage in its effect on the course of the disease.

9. Treatment does not lead to the eradication (elimination) of the human papillomavirus and does not always affect the frequency and severity of subsequent recurrences.

10. To confirm cure, a follow-up medical examination is required one month after the destruction of anogenital (venereal) warts.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not used.