Penile warts are the most common sexually transmitted disease in men and are caused by the human papillomavirus (HPV). Penile warts usually present as soft, flesh-colored to brown plaques on the glans and body of the penis.
To provide up-to-date information on the current understanding, diagnosis, and treatment of penile warts, a review was performed using key terms and phrases such as "penile warts" and "genital warts. "The search strategy included meta-analysis, randomized controlled trials, clinical trials, observational studies and reviews.
Epidemiology
HPV infection is the most common sexually transmitted disease in the world. HPV infection does not mean that a person will develop genital warts. It is estimated that 0. 5 - 5% of sexually active young adult men have genital warts on physical examination. The peak age of the disease is 25 - 29 years.
Etiopathogenesis
HPV is a non-enveloped capsid double-stranded DNA virus belonging to the Papillomavirus genus of the Papillomaviridae family and infects only humans. The virus has a circular genome of 8 kilobases in length, which encodes eight genes, including the genes for two encapsulating structural proteins, namely L1 and L2. The virus-like particle containing L1 is used in the production of HPV vaccines. L1 and L2 mediate HPV infection.
It is also possible to be infected with different types of HPV at the same time. In adults, genital HPV infection is transmitted primarily through sexual contact and, less commonly, through oral sex, skin-to-skin, and fomites. In children, HPV infection can occur as a result of sexual abuse, vertical transmission, self-infection, infection through close domestic contact and through fomites. HPV penetrates the cells of the basal layer of the epidermis through microtraumas on the skin or mucous membrane.
The incubation period of the infection varies from 3 weeks to 8 months, on average 2 - 4 months. The disease is more common in individuals with the following predisposing factors: immune deficiency, unprotected intercourse, multiple sexual partners, a sexual partner with multiple sexual partners, a history of sexually transmitted infections, early sexual activity, a shorter period of time between meeting a newpartner and having intercourse, living with him, not being circumcised and smoking. Other predisposing factors are moisture, maceration, trauma and epithelial defects in the penile area.
Histopathology
Histologic examination revealed papillomatosis, focal parakeratosis, severe acanthosis, numerous vacuolated koilocytes, vascular distension, and large keratohyaline granules.
Clinical manifestations
Penile warts are usually asymptomatic and can sometimes cause itching or pain. Genital warts are usually found on the frenulum, the glans penis, the inner surface of the foreskin, and the coronal sulcus. At the onset of the disease, penile warts usually appear as small, discrete, soft, smooth, pearly, dome-shaped papules.
Lesions may appear singly or in groups (clustered). They can be stalked or broad-based (sedentary). Over time, the papules may coalesce into plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebral, fungal, or cauliflower-shaped. The color may be flesh-colored, pink, erythematous, brown, violet, or hyperpigmented.
Diagnosis
Diagnosis is made clinically, usually based on history and examination. Dermoscopy and in vivo confocal microscopy help improve diagnostic accuracy. Morphologically, warts can vary from finger-shaped and epiphyseal to mosaic. Among the features of vascularization can be found glomerular, hairpin and punctate vessels. Papillomatosis is an integral feature of warts. Some authors suggest the use of an acetic acid test (whitening of the wart surface when acetic acid is applied) to facilitate the diagnosis of penile warts.
The sensitivity of this test is high for hyperplastic penile warts, but for other types of penile warts and subclinical infected areas the sensitivity is considered low. Skin biopsy is rarely warranted but should be considered in the presence of atypical features (eg, atypical pigmentation, induration, attachment to underlying structures, firm consistency, ulceration, or bleeding), when the diagnosis is uncertain, or for warts that are refractory to varioustreatments. Although some authors suggest PCR diagnostics, among other things, to determine the HPV type that determines the risk of malignancy, HPV typing is not recommended in routine practice.
Differential diagnosis
Differential diagnosis includes penile pearly papules, Fordyce granules, acrochordons, broad condylomas of syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, capillary varicose lymphangioma, lymphogranuloma venereum, scabies, syringoma, posttraumatic neuroma. , schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesIt presents as asymptomatic, small, smooth, soft, yellowish, pearly white or flesh-colored, conical or dome-shaped papules 1 - 4 mm in diameter. The lesions are usually uniform in size and shape and symmetrically distributed. The papules are usually located in single, double or multiple rows in a circle around the crown and groove of the glans penis. Papules are usually more noticeable on the back of the crown and less noticeable towards the frenulum.
Fordyce granules- these are enlarged sebaceous glands. On the glans and body of the penis, Fordyce granules appear as asymptomatic, isolated or clustered, discrete, creamy yellow, smooth papules 1 - 2 mm in diameter. These papules are more noticeable on the shaft of the penis during erection or when the foreskin is pulled. Sometimes a thick chalky or cheese-like material can be oozed out of these granules.
Acrochordons, also known as skintags ("skin tags"), are soft, flesh-colored to dark brown, pedunculated or broad skin growths with a smooth outline. Sometimes they may be hyperkeratotic or have a wartlike appearance. Most acrochordons are between2 and 5 mm, although sometimes they can be larger, especially in the groin. Acrochordons can appear on almost any part of the body, but are most often seen on the neck and intertriginous areas. When they appear in the penile area, they can mimic penile warts.
Broad condylomas- These are skin lesions in secondary syphilis caused by the spirochete Treponema pallidum. Clinically, broad condylomas appear as moist, gray-white, velvety, flat or cauliflower-like, broad papules or plaques. They tend to develop in warm, moist areas of the genitals and perineum. Secondary syphilis is characterized by a nonpruritic, diffuse, symmetrical maculopapular rash on the trunk, palms, and soles. Systemic manifestations include headache, fatigue, pharyngitis, myalgia, and arthralgia. Erythematous or whitish rashes on the oral mucosa, as well as alopecia and generalized lymphadenopathy, may occur.
Granuloma annulareis a benign, self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, firm, brown-purple, erythematous or flesh-colored papules, usually arranged in a ring. As the condition progresses, central involution may be seen. A ring of papules often grows together to form an annular plaque. The granuloma is usually found on the extensor surfaces of the distal limbs, but may also be found on the body and glans of the penis.
Lichen planus of the skinis a chronic inflammatory dermatosis presenting as flat, polygonal, purple, itchy papules and plaques. Most often, the rash appears on the flexor surfaces of the arms, back, torso, legs, ankles and glans. Approximately 25% of lesions occur on the genitals.
Epidermal nevusis a hamartoma arising from embryonic ectoderm that differentiates into keratinocytes, apocrine glands, eccrine glands, hair follicles, and sebaceous glands. The classic lesion is a single, asymptomatic, well-circumscribed plaque that follows the lines of Blaschko. The onset of the disease usually occurs in the first year of life. The color varies from flesh to yellow and brown. Over time, the lesion may thicken and become a wart.
Capillary varicose lymphangioma is a benign sac-like enlargement of skin and subcutaneous lymph nodes. The condition is characterized by clusters of blisters resembling frog roe. The color depends on the content: a whitish, yellow or light brown color is due to the color of the lymph fluid, and a reddish or bluish color is due to the presence of red blood cells in the lymph fluid as a result of hemorrhage. Blisters can undergo changes and take on the appearance of warts. They are most often found on the extremities, less often in the genital area.
Venereal lymphogranulomais a sexually transmitted disease caused by Chlamydia trachomatis. The disease is characterized by a transient painless genital papule and, less commonly, an erosion, ulcer or pustule, followed by inguinal and/or femoral lymphadenopathy known as buboes.
usuallysyringomasare asymptomatic, small, soft or firm, flesh-colored or brown papules 1 - 3 mm in diameter. They are usually found in the periorbital areas and on the cheeks. However, syringomas can occur on the penis and buttocks. When found on the penis, syringomas can be mistaken for penile warts.
Schwannoma- These are neoplasms originating from Schwann cells. Penile schwannoma usually presents as a solitary, asymptomatic, slow-growing nodule on the dorsal aspect of the penis.
Bowenoid papulosisis a precancerous focal intraepidermal dysplasia that usually presents as multiple red-brown papules or plaques in the anogenital area, especially the penis. The pathology was consistent with squamous cell carcinoma in situ. Progression to invasive squamous cell carcinoma occurs in 2 to 3% of cases.
usuallysquamous cell carcinomapenis manifests itself in the form of a nodule, ulcer or erythematous lesion. The rash may look like a wart, leukoplakia, or sclerosis. The most preferred site is the head of the penis, followed by the foreskin and the body of the penis.
Complications
Penile warts can cause significant anxiety or distress to the patient and their sexual partner due to their cosmetic appearance and contagiousness, stigmatization, concerns about future fertility and cancer risk, and their association with other sexually transmitted diseases. It is estimated that 20 - 34% of affected patients have an underlying sexually transmitted disease. Patients often experience feelings of guilt, shame, low self-esteem and fear. People with penile warts have higher rates of sexual dysfunction, depression and anxiety compared to the healthy population. This condition can have a negative psychosocial impact on the patient and negatively affect their quality of life. Large exophytic lesions may bleed, cause urethral obstruction, and interfere with intercourse. Malignant transformation is rare except in immunocompromised individuals. Patients with penile warts are at increased risk of developing anogenital cancer, head cancer, and neck cancer as a result of coinfection with high-risk HPV.
Forecast
If left untreated, genital warts may disappear on their own, remain unchanged, or increase in size and number. Approximately one-third of penile warts regress without treatment, and the average time until they disappear is approximately 9 months. With proper treatment, 35 to 100% of warts disappear within 3 to 16 weeks. Although the warts disappear, the HPV infection may remain, leading to recurrence. Relapse rates ranged from 25 to 67% within 6 months of treatment. Among patients with subclinical infection, recurrent infection (reinfection) after sexual intercourse, and in the presence of immunodeficiencies, a higher rate of recurrence is observed.
Treatment
Active treatment of penile warts is preferable to follow-up because it results in faster resolution of lesions, reduces fears of partner infection, alleviates emotional stress, improves cosmetic appearance, reduces social stigma associated with penile lesions, and relievessymptoms (eg itching, soreness or bleeding). Penile warts that persist for more than 2 years are much less likely to go away on their own, so active treatment should be offered first. Counseling of sexual partners is mandatory. Screening for sexually transmitted diseases is also recommended.
Active treatments can be divided into mechanical, chemical, immunomodulatory and antiviral. There are very few detailed comparisons of different treatment methods with each other. Effectiveness varies depending on the treatment method. To date, no treatment has been shown to be consistently better than other treatments. The choice of treatment should depend on the skill level of the doctor, the patient's preferences and tolerance to treatment, as well as the number of warts and the severity of the disease. Comparative effectiveness, ease of administration, side effects, cost and affordability of treatment should also be taken into account. In general, self-medication is considered less effective than self-medication.
The patient receives treatment at home (according to the doctor's prescription)
Treatment methods used in the clinic
Methods used in the clinic include podophyllin, liquid nitrogen cryotherapy, bichloroacetic acid or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy.
Liquid Podophyllin 25%, derived from podophyllotoxin, works by arresting mitosis and causing tissue necrosis. The drug is applied directly to the penile wart once a week for 6 weeks (maximum 0. 5 ml per treatment). Podophyllin should be washed off 1 to 4 hours after treatment and should not be applied to areas of high skin moisture. The effectiveness of removing warts reaches 62%. Because of reports of toxicity, including death, associated with podophyllin use, podofilox, which has a much better safety profile, is considered preferred.
Liquid nitrogen, the treatment of choice for penile warts, can be applied using a spray bottle or cotton-tipped applicator directly on and 2mm around the wart. Liquid nitrogen causes tissue damage and cell death by rapidly freezing to form ice crystals. The minimum temperature required to kill warts is -50°C, although some authors believe that -20°C is also effective.
The effectiveness of removing warts reaches 75%. Side effects include pain during treatment, erythema, desquamation, blistering, erosion, ulceration, and dispigmentation at the application site. A recent phase II parallel randomized trial in 16 Iranian men with genital warts showed that cryotherapy using Wartner's formulation containing a mixture of 75% dimethyl ether and 25% propane was also effective. Further research is needed to confirm or refute this conclusion. It must be said that cryotherapy using Wartner's composition is less effective than liquid nitrogen cryotherapy.
Bichloroacetic acid and trichloroacetic acid can be used to treat small penile warts because their ability to penetrate the skin is limited. Each of these acids works by coagulation of protein, followed by cell destruction and subsequent removal of the penile wart. A burning sensation may occur at the site of application. Relapses after using bichloroacetic or trichloroacetic acid occur as often as with other methods. Medicines can be used up to three times a week. Wart removal efficiency ranges from 64 to 88%.
Electrocoagulation, laser therapy, carbon dioxide laser or surgical excision work by mechanically destroying the wart and can be used in cases where there is a rather large wart or a group of warts that are difficult to remove with conservative treatment methods. Mechanical methods of treatment have the highest percentage of effectiveness, but with their use there is a higher risk of scarring the skin. Local anesthesia applied to unoccluded lesions 20 minutes before the procedure or a mixture of local anesthetics applied to occluded lesions one hour before the procedure should be considered as measures to reduce discomfort and pain during the procedure. General anesthesia may be used for surgical removal of large lesions.
Alternative treatments
Patients who do not respond to first-line treatment may respond to other treatments or a combination of treatments. Second-line therapy includes topical, intralesional, or intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
Antiviral therapy with cidofovir may be considered in immunocompromised patients with treatment-refractory warts. Cidofovir is an acyclic nucleoside phosphonate that competitively inhibits viral DNA polymerase, thereby preventing viral replication.
Side effects of topical (intralesional) cidofovir include irritation, erosion, post-inflammatory pigmentary changes, and superficial scarring at the application site. The main side effect of intravenous cidofovir is nephrotoxicity, which can be prevented with hydration with saline and probenecid.
Prevention
Genital warts can be prevented to some extent by delaying sexual activity and limiting the number of sexual partners. Latex condoms, when used consistently and correctly, reduce the transmission of HPV. Sexual partners with anogenital warts should be treated.
HPV vaccines are effective before sexual activity for primary prevention of infection. This is because the vaccines do not provide protection against diseases caused by vaccine types of HPV that the individual has acquired through previous sexual activity. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the American Academy of Family Practice, and the International Human Papillomavirus Society recommend routine vaccination of girls and boys with the HPV vaccine.
The target age for vaccination is 11 - 12 years for girls and boys. The vaccine can be administered at the earliest age of 9 years. Three doses of HPV vaccine should be given at month 0, months 1 to 2 (usually 2), and month 6. Catch-up vaccination is indicated for males younger than 21 years and females younger than 26 years if they were not vaccinated at the target age. Vaccination is also recommended for men who are homosexual or immunocompetent under the age of 26 if they have not previously been vaccinated. Vaccination reduces the likelihood of HPV infection and the subsequent development of warts and penile cancer. Vaccinating both men and women is more helpful in reducing the risk of penile genital warts than vaccinating only men because men can get HPV from their sexual partners. The prevalence of anogenital warts decreased significantly from 2008 to 2014 due to the introduction of the HPV vaccine.
Conclusion
Penile warts are a sexually transmitted disease caused by HPV. This pathology can have a negative psychosocial impact on the patient and negatively affect his quality of life. Although approximately one-third of penile warts disappear without treatment, active treatment is preferred to speed resolution of the warts, reduce fears of infection, reduce emotional distress, improve cosmetic appearance, reduce the social stigma associated with the lesions ofpenis, and relieve symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral, and often combined. So far, no treatment has been proven to be better than the others. The choice of treatment method should depend on the doctor's level of mastery of this method, the patient's preferences and tolerability of the treatment, as well as the number of warts and the severity of the disease. Comparative effectiveness, ease of use, side effects, cost and affordability of treatment should also be taken into account. HPV vaccines before sexual activity are effective for primary prevention of infection. The target age for vaccination is 11 - 12 years for both girls and boys.