Penile warts are the most common sexually transmitted disease in men and are caused by the human papillomavirus (HPV). Penile warts usually appear as soft, flesh-colored to brown patches on the glans and shaft of the penis.
To take stock of the current understanding, diagnosis and treatment of penile warts, a review was conducted using key terms and phrases such as "penile warts" and "genital warts". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies and reviews.
Epidemiology
HPV infection is the most common sexually transmitted disease worldwide. HPV infection does not mean that a person will develop genital warts. It is estimated that 0. 5 to 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 double-stranded capsid DNA virus belonging to the genus Papillomavirus of the Papillomaviridae family and only infects humans. The virus has a circular genome of 8 kilobases in length, which encodes eight genes, including the genes for two structural encapsulating 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 through sexual abuse, vertical transmission, autoinfection, infection through close household contact, and through fomites. HPV enters the cells of the basal layer of the epidermis through microtrauma to the skin or mucous membranes.
The incubation period of infection ranges from 3 weeks to 8 months, with an average of 2 to 4 months. The disease is more common in individuals with the following predisposing factors: immunodeficiency, unprotected sexual intercourse, multiple sexual partners, sexual partner with multiple sexual partners, history of sexually transmitted infections, early sexual activity, shorter period of time betweenmeeting a sexual partner. new partner and having sex, living with him, not being circumcised and smoking. Other predisposing factors are humidity, maceration, trauma and epithelial defects in the penile region.
Histopathology
Histologic examination reveals papillomatosis, focal parakeratosis, severe acanthosis, multiple vacuolated koilocytes, vascular distension, and large keratohyalin granules.
Clinical manifestations
Penile warts are usually asymptomatic and may occasionally be itchy or painful. Genital warts are generally located on the frenulum, the glans, the inner surface of the foreskin and the coronal furrow. At the onset of the disease, penile warts usually appear as small, inconspicuous, soft, smooth, pearly, dome-shaped papules.
Lesions can occur individually or in clusters (grouped together). They can be pedunculated or broad-based (sessile). Over time, the papules may coalesce into plaques. Warts can be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungiform or cauliflower-shaped. The color may be flesh, pink, erythematous, brown, purple or hyperpigmented.
Diagnostic
The diagnosis is made clinically, usually on the basis of history and examination. Dermoscopy and in vivo confocal microscopy help to improve diagnostic accuracy. Morphologically, warts can vary from digital and pineal to mosaic. Characteristics of the vasculature include glomerular, hairpin, and punctate vessels. Papillomatosis is an integral part of warts. Some authors suggest using the acetic acid test (whitening of the wart surface when acetic acid is applied) to aid in 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 (e. g. , atypical pigmentation, induration, attachment to underlying structures, hard consistency, ulceration, or bleeding), when the diagnosis is uncertain, or for warts refractory tovarious treatments. Although some authors propose a PCR diagnosis to, among other things, determine the HPV type determining the risk of malignancy, HPV typing is not recommended in current practice.
Differential diagnosis
Differential diagnosis includes pearly penile papules, Fordyce granules, skin tags, condyloma lata in syphilis, molluscum contagiosum, granuloma annulare, lichen planus, lichen planus, seborrheic keratosis, epidermal nevus, lymphangiomavaricose veins, lymphogranuloma venereum, scabies, syringoma, post-traumatic neuroma. , schwannoma, bowenoid papulosis and squamous cell carcinoma.
Pearly penile papulesPresent as asymptomatic, small, smooth, soft, yellowish, pearly white or flesh-colored, conical or dome-shaped papules, 1 to 4 mm in diameter. Lesions are usually uniform in size and shape and symmetrically distributed. Typically, papules are located in single, double or multiple rows in a circle around the crown and furrow of the glans. Papules tend to be more visible on the back of the crown and less visible towards the frenulum.
Fordyce Pellets- these are hypertrophied sebaceous glands. On the glans and shaft of the penis, Fordyce granules appear as asymptomatic papules, isolated or grouped, discrete, creamy yellow, smooth, with a diameter of 1 to 2 mm. These papules are most visible on the shaft of the penis during erection or when the foreskin is pulled. Sometimes a dense, chalky or cheese-like material can be extracted from these granules.
Skin tags, also known as skin tags ("skin tags"), are soft, flesh-colored to dark brown, stalked or broad-based skin growths with a smooth outline. Sometimes they can be hyperkeratotic or have a warty appearance. Most skin tags measure between 2 and 5 mm in diameter, although they can sometimes be larger, especially in the groin. Skin tags can appear on almost any part of the body, but are most commonly seen on the neck and intertriginous areas. When they appear in the penis area, they can mimic penile warts.
Condyloma lata- These are skin lesions of secondary syphilis caused by the spirochete Treponema pallidum. Clinically, condyloma lata presents as large, moist, gray-white, velvety, flat or cauliflower-like papules or plaques. They tend to develop in warm, moist areas of the genitals and perineum. Secondary syphilis is characterized by a non-pruritic, diffuse, symmetrical maculopapular rash on the trunk, palms, and soles of the feet. Systemic manifestations include headache, fatigue, pharyngitis, myalgia, and arthralgia. Erythematous or whitish rashes on the oral mucosa may occur, as well as alopecia and generalized lymphadenopathy.
Granuloma annulareis a benign, self-limiting inflammatory disease of the dermis and subcutaneous tissue. The pathology is characterized by asymptomatic, firm, brownish purple, erythematous or flesh-colored papules, usually arranged in a ring. As the disease progresses, central involution may be noted. A ring of papules often grows together to form a ring-shaped plaque. The granuloma is usually located on the extensor surfaces of the distal extremities, but can also be detected on the shaft and glans penis.
Lichen planus of the skinis a chronic inflammatory dermatosis manifested by flat, polygonal, purple and itchy papules and plaques. Most often, the rash appears on the flexor surfaces of the hands, back, torso, legs, ankles and glans. About 25% of lesions occur in the genitals.
Epidermal nevusis a hamartoma arising from the embryonic ectoderm that differentiates into keratinocytes, apocrine glands, eccrine glands, hair follicles and sebaceous glands. The classic lesion is a solitary, asymptomatic, well-circumscribed plaque that follows Blaschko's lines. The disease usually appears during the first year of life. Color varies from flesh to yellow and brown. Over time, the lesion may thicken and become warty.
Capillary varicose lymphangioma is a benign saccular dilatation of the cutaneous and subcutaneous lymph nodes. The disease is characterized by clusters of blisters resembling frog spawn. The color depends on the content: the whitish, yellow or light brown color is due to the color of the lymphatic fluid, and the reddish or bluish color is due to the presence of red blood cells in the lymphatic fluid following hemorrhage. The blisters may change and take on a warty appearance. It is most often found on the extremities, less often in the genital area.
Lymphogranuloma venereumis a sexually transmitted disease caused by Chlamydia trachomatis. The disease is characterized by a transient, painless genital papule and, more rarely, by erosion, ulcer or pustule followed by inguinal and/or femoral lymphadenopathy known as buboes.
Generally,syringomasare asymptomatic, small, soft or dense, flesh-colored or brown papules, measuring 1 to 3 mm in diameter. They are generally found in the periorbital areas and on the cheeks. However, syringomas can appear on the penis and buttocks. When located on the penis, syringomas can be confused with penile warts.
Schwannomas- These are neoplasms originating from Schwann cells. Penile schwannoma usually presents as a single, asymptomatic, slow-growing nodule on the dorsal aspect of the penile shaft.
Bowenoid papulosisis a precancerous focal intraepidermal dysplasia that usually appears as multiple red-brown papules or plaques in the anogenital region, particularly in the penis. The pathology is compatible with squamous cell carcinoma in situ. Progression to invasive squamous cell carcinoma occurs in 2 to 3% of cases.
Generally,squamous cell carcinomathe penis manifests itself in the form of a nodule, ulcer or erythematous lesion. The rash may appear warty, leukoplakia, or sclerotic. The most favored site is the glans, followed by the foreskin and the shaft of the penis.
Complications
Penile warts can be a source of significant worry or distress to the patient and their sexual partner because of their cosmetic appearance and contagiousness, stigma, concerns about future fertility and cancer risk, andtheir association with other sexually transmitted diseases. It is estimated that 20 to 34% of affected patients have underlying sexually transmitted diseases. 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 than 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 sexual 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 due to high-risk HPV co-infection.
Forecast
If no treatment is given, genital warts may disappear on their own, remain unchanged, or increase in size and number. Around a third of penile warts regress without treatment and the average time until they disappear is around 9 months. With proper treatment, 35 to 100% of warts disappear within 3 to 16 weeks. Even if the warts go away, the HPV infection may persist, leading to a recurrence. Relapse rates range 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 percentage of relapses occurs.
Treatment
Active treatment of penile warts is preferable to aftercare because it results in faster resolution of the lesions, reduces fear of infecting a partner, relieves emotional stress, improves cosmetic appearance, reduces social stigma associated with penile lesions, andrelieves symptoms (e. g. itching, pain 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 sexual partners is mandatory. Screening for sexually transmitted diseases is also recommended.
Active treatments can be divided into mechanical, chemical, immunomodulatory and antiviral treatments. 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 superior to 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 availability of treatment should also be considered. In general, self-administered treatment is considered less effective than self-administered treatment.
The patient carries out the treatment at home (as prescribed by the doctor)
Treatment methods used in the clinic
Methods used clinically include podophylline, 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 stopping mitosis and causing tissue necrosis. The medicine 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 very moist areas of the skin. The effectiveness of wart removal reaches 62%. Due to reports of toxicity, including deaths, associated with podophyllin use, podofilox, which has a much better safety profile, is considered preferred.
Liquid nitrogen, the method of choice for treating penile warts, can be applied using a spray bottle or cotton-tipped applicator directly to and 2 mm around the wart. Liquid nitrogen causes tissue damage and cell death by rapidly freezing to form ice crystals. The minimum temperature required to destroy warts is -50°C, although some authors believe that -20°C is also effective.
The effectiveness of wart removal reaches 75%. Side effects include pain during treatment, erythema, scaling, blistering, erosion, ulceration and depigmentation at the application site. A recent parallel randomized phase II trial in 16 Iranian men with genital warts showed that cryotherapy using the Wartner 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 cryotherapy using liquid nitrogen.
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 coagulating the proteins, then destroying the cells and thus eliminating the penile wart. A burning sensation may occur at the application site. Relapses after using bichloroacetic or trichloroacetic acid occur as often as with other methods. The medications can be used up to three times a week. The effectiveness of wart removal 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 fairly large wart or a group of warts that are difficult to remove withconservative treatment methods. Mechanical treatment methods have the highest percentage of effectiveness, but their use carries a higher risk of scarring the skin. Local anesthesia applied to non-occluded 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 can be used to surgically remove large lesions.
Alternative treatments
Patients who do not respond to first-line treatments may respond to other treatments or a combination of treatments. Second-line treatment includes topical, intralesional, or intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.
Antiviral treatment with cidofovir may be considered in immunocompromised patients with warts refractory to treatment. 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 avoided with saline hydration and probenecid.
Prevention
Genital warts can be avoided to some extent by delaying sexual activity and limiting the number of sexual partners. Latex condoms, when used regularly 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 vaccines do not provide protection against disease caused by vaccine types of HPV contracted by an individual 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 vaccinationroutinely vaccinate girls and boys with the HPV vaccine.
The target age for vaccination is 11 to 12 years for girls and boys. The vaccine can be administered from the age of 9. Three doses of HPV vaccine should be given at month 0, months 1 to 2 (usually 2), and 6 months. Catch-up vaccination is indicated for men under 21 and women under 26 if they were not vaccinated at the target age. Vaccination is also recommended for homosexual or immunocompetent men under 26 years of age, if they have not been previously vaccinated. Vaccination reduces the risk of becoming infected with HPV and subsequently developing penile warts and penile cancer. Vaccinating both men and women is more beneficial in reducing the risk of genital penile warts than vaccinating only men, since men can acquire HPV infection from their sexual partners. The prevalence of anogenital warts decreased significantly between 2008 and 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 harm their quality of life. Although approximately one third of penile warts go away without treatment, active treatment is best to hasten resolution of warts, reduce fears of infection, reduce emotional distress, improve cosmetic appearance, reduce social stigma associated with the lesionspenis and relieve symptoms.
Active treatment methods can be mechanical, chemical, immunomodulatory and antiviral, and often combined. So far, no treatment has been shown to be superior to others. The choice of treatment method should depend on the level of skill of the doctor in this method, 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 use, side effects, cost and availability of treatment should also be considered. HPV vaccines before sexual activity are effective in primary prevention of infection. The target age for vaccination is 11 to 12 years for girls and boys.