Vulvo Vaginal Warts: How to Manage?
Year: 2024
Type: article
Abstract: Introduction Anogenital human papillomavirus (HPV) infection presents as anogenital warts. HPV Infection can cause papules or plaque-like lesions in the vulva, vagina, external genitalia, perineum, perianal region, and groin region. The causative serotypes of HPV in most of the cases are HPV 6 and 11. Etiopathogenesis Genital skin contact is the postulated mode of transmission of HPV infection. Micro abrasions in the epidermal layers of skin provide the nidus for HPV infection. Anogenital warts are not mandatory for transmission of HPV infection, but the presence of anogenital warts is a high-risk condition for spreading infection since they have a high viral load. The incubation period for HPV infection of warts is usually 3 weeks–8 months. Among women with HPV 6 and 11 infection ~64% develop anogenital warts. Reported incidence from various literature is about 0.2%–5.1% and is more common among young adults.[1,2] Vertical transmission of HPV 6 and 11 from mother to child has been reported to present as Juvenile respiratory papillomatosis. Neonatal inoculation possibly occurred during passage through the birth canal; hence, caesarean section was recommended as a potential way to avoid the risk, but possible antenatal transmission has also been suggested. Immunosuppression and smoking are found to increase the risk of recurrence, whereas circumcision is said to be proactive. In the natural course, many lesions resolve on their own in <4 months, but the disappearance of the lesion does not indicate the absence of the virus in the susceptible area. Recurrence with permissible environments such as mechanical irritation, trauma to genital skin, immunosuppression, and systemic or local inflammatory conditions occur.[1,2] Malignant transformation has been reported in immunosuppressed individuals. Clinical manifestation and diagnosis Clinical examination clinches the diagnosis. They present with solitary or multiple soft, plaque-like, or warty lesions in the anogenital area. Other skin lesions, such as Lichen planus, Lichen sclerosis, and molluscum contagiosum, seborrheic keratosis, condyloma lata of syphilis that occur in the genital skin must be differentiated.[3] Examination for coexisting other sexually transmitted infections and premalignant lesions of the vulva, vagina, and cervix. If the diagnosis is uncertain biopsy may help in those patients with atypical presentation such as hyperpigmentation, vascularity, ulceration, and sudden increase in size. In refractory cases biopsy will help to rule out malignancy, especially in immunosuppressed and postmenopausal women. Biopsy should be taken from the most abnormal area including the base of the lesion from its edge. Testing for HPV virus is not mandatory as it may not change the course of treatment, but it may show coinfection with other high-risk HPV types which could have or may cause premalignant lesions of vulva, vagina or cervix. Vulvoscopy with acetic acid application may not help to differentiate the lesions from other benign lesions. Sexual partners need to be advised to get tested. Involvement of neighboring sites such as urethral meatus, lower urethra, and anus is not uncommon. Lesions in upper urethra and bladder has also been reported. Management Anogenital warts may regress spontaneously over 4 months but patients in whom resolution occurs are not predictable. Due to anxiety and discomfort, patients may seek treatment. All patients should be offered treatment since the lesion may progress or increase in size making the treatment difficult. Treatment options may be patient applied or physician administered. The choice of treatment depends on patient preference, duration of symptoms, any prior treatment, cost, and availability. Patients need to be counseled about the causative organism and the risk of spreading to partner(s). Most of the time patients are more concerned about the source of HPV infection and duration since when the subject harbors the organism. Marital discordance due to fear of promiscuity of the partner is common. The patient may be concerned about the risk of recurrence and cosmetic outcomes of the management options. Explaining the method to apply medication in a patient-applied approach and the pictorial/video demonstration of the procedure in a physician-administered method helps to alley the anxiety and to get the best results. First-line Therapies First-line therapies in patient-applied methods include the application of topical medications – imiquimod, podophyllotoxin, sinecatechins. Imiquimod and sinecatechins, act by their local immunomodulatory effects. Podophyllotoxin acts by its antiproliferative property. Using topical medicines depends on the number, location, and size of the warts, cost and availability of medication. The patient’s ability to apply medicine in the prescribed way decides the outcome. The above drugs are recommended for use in anogenital warts than vaginal warts since the application and prevention of contact from normal area is difficult with vaginal warts. Imiquimod – It is an immunomodulatory drug, stimulating production of interferon-alpha, tumor necrosis factor, and interleukin (IL) 1, IL-6, and IL-8. Imiquimod 5% cream and 3.75% cream are available for the treatment of anogenital warts. Imiquimod 5% cream is applied thrice weekly, maximum for 16 weeks and imiquimod 3.75% cream applied daily for 8 weeks if lesion still present for additional 8 weeks. A thin layer of imiquimod cream should be applied to each wart and rubbed in until the cream is no longer visible. Imiquimod cream should be applied before bed time and left for 6–10 h. The area of application is washed with mild soap and water after the duration of application. The most common adverse effects are local redness, induration, erosion, or vesical formation more with 5% than 3.75% cream. If symptoms are severe treatment may be stopped for a period and resumed once symptoms subside. Occasionally, hypopigmentation and flu-like symptom may also occur[4-8] Podophyllotoxin – Podophyllotoxin is an antimitotic drug available in strengths of 0.5% and 0.15%. The drug is applied over the lesions (not more than 10 cm2 and volume <0.5 mL/day) 3 days consecutively, followed by 4 drug-free days. This weekly schedule is repeated up to four times. In order to reduce the irritation the area is usually washed 2–4 h after application. Podophyllin should not be applied over any raw wound. The most common adverse effects are pain or burning over the applied area. Systemic side effects like headache has been reported with excessive application[5,9,10] Sinecatechins – This ointment is prepared from partially purified fraction of the water extract of green tea leaves (Camellia sinensis), available in 10% and 15% formulations. The mechanism of action is not clear. Postulated mechanisms of action are the upregulation of apoptosis-associated genes and downregulation of the proinflammatory milieu to HPV. Ointment strand of 0.5 cm is applied over each wart covering it completely using finger. Ointment can be left without washing at the applied site. The treatment completed till all the lesions disappear or maximum of 16 weeks. It may cause local erythema[11,12] During the local treatment with above drugs, sexual intercourse should be avoided. First-line clinician administered therapies This includes cryotherapy, trichloroacetic acid (TCA), and bichloroacetic acid (BCA), topical interferons, surgical excision, electrosurgery, and laser therapy. Clinician administered treatments has short treatment time.[5,13] In cryotherapy, liquid nitrogen is applied over the lesion, including 1 mL of surrounding normal skin, using a cotton bud or with a spray gun device. Two freeze-thaw cycles are completed in a sitting, and if clearance is incomplete, the cycle is repeated after 2 weeks. Side effects include pain and burning sensation during the procedure. The procedure may cause pigmentary changes, scarring, temporary hypoesthesia, or hyperesthesia[9,14] Similarly in electrosurgery procedures, local anesthesia is given and the lesions are desiccated. Compared to cryotherapy high clearance rates have been reported with electrocautery but depigmentation and scarring are more. The procedure needs to be performed with due precautions to reduce transmission Small warts may be treated with TCA, an inexpensive caustic agent destroying the warts through coagulation of proteins. 80% or 90% TCA is applied directly to the warts with a cotton tip applicator in small quantity and allowed to dry. A white frost becomes visible at the treatment site. Drug is applied once weekly for 3–4 weeks or once in 2 weeks for 8–10 weeks. BCA works similar to TCA and applied in the same way. Excessive application can be neutralized by giving soap water or sodium bicarbonate wash. Application of petroleum jelly or vaseline to surrounding normal skin can help to reduce damage to the normal skin Interferons: Both alpha and beta interferons have been tried to treat vulvovaginal warts topically and intralesional injections in subcutaneous plane. The dosing for intralesional injection at wart site is 0.5–1.5 million IU per lesion, administered weekly twice or thrice for 3 weeks under local anesthesia. The course can be repeated if required after 12–16 weeks. Most common side effects with interferons in any route are local pain, flu-like symptoms, fatigue, loss of appetite. Interferons are usually chosen as second line treatment since the side effects are bothersome For patients with large lesions (>1 cm) surgical excision to the depth of superficial dermis gives good results. The procedure needs local anesthesia and pain may persist till healing, i.e. another 4 weeks.[13,15] Carbon dioxide LASER has been used similar to surgical excision. Nd:YAG: LASER has been used to treat urethral warts. Second-line Therapy In patients in whom one of the first-line therapies has failed, using alternate first-line therapy alone or in combination is an option. Cryotherapy followed by topical administration of first-line medicines is most commonly practiced. Podophyllin resin and topical fluorouracil can be effective for external anogenital warts but are not recommended as first-line treatments because of side effects. Few studies have reported cure with topical use of podophyllin resin, 5-fluorouracil and cantharidin. In patients with refractory disease intralesional cidofovir, intralesional interferon, systemic low-dose oral cyclophosphamide, has been tried. Follow-up Patients with anogenital warts are prone for recurrence after successful therapy. HPV may persist in genital skin in women who have been treated successfully. HPV vaccine may not cure the condition but may protect against other serotypes of HPV which patient may get exposed. Screening for cervical cancer as per the recommendation is advised. Conveying the partner of the patient about the infection and examining him for genital warts or other sexullay transmitted diseases (STD) is recommended.[16] Newer Treatment Methods Under Research Topical application of sodium nitrate with citric acid, topical nitric-zinc complex, immunostimulant food supplements, photodynamic therapy, Mycobacterium w vaccine, Mycobacterium indicus pranii immunotherapy and acitretin has been studied. These drugs need further validation before treatment.[17,18] Special Situations Pregnancy with genital warts Podofilox, podophyllin, and sinecatechins should not be used during pregnancy. Data for imiquimod are not adequate to recommend its use during pregnancy. Surgical removal can be considered if the lesion become larger and friable during pregnancy, which may not give complete resolution. The mode of transmission to child during pregnancy and parturition are not only direct contact during parturition but also through transplacental, perinatal, or postnatal time. Hence, the role of cesarean delivery prevents respiratory papillomatosis among infants and children also is unclear.[19] HIV and other immunosuppressed conditions More incidences of anogenital warts are noted in HIV and immunosuppressed individuals. They present with larger and more number of lesions. The lesions may be difficult to treat and recur early. Biopsy of the lesion when it is large and resistant to treatment is recommended to rule out underlying malignancy.[20] Vulvo vaginal warts when coincident with cervical high-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions in biopsy of an atypical wart: Referral to gynecologic oncology units or specialist with expertise is recommended for management. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Institution: Cancer Institute (WIA)
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4408071635