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I INTRODUCTION

I.1 Definition Condyloma acuminatum refers to an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV). More than 100 types of double-stranded HPV papovavirus have been isolated. Many of these have been related directly to an increased neoplastic risk in men and women.1 Approximately 90% of condyloma acuminata are related to HPV types 6 and 11. These 2 types are the least likely to have a neoplastic potential. Risk for neoplastic conversion has been determined to be moderate (types 33, 35, 39, 40, 43, 45, 51-56, 58) or high (types 16, 18),2 with many other isolated types. The picture is complicated by proven coexistence of many of these types in the same patient (10-15% of patients), the lack of adequate information on the oncogenic potential of many other types, and ongoing identification of additional HPV-related clinical pathology. I.2 Prevalence Annual incidence of condyloma acuminatum is 1% in United States. It is considered the most common sexually transmitted disease (STD). Prevalence has been reported to exceed 50%. Highest prevalence and risk is among young adults in the third decade and in older teenagers. A 4-fold or more increase in prevalence has been reported in the last 2 decades. International prevalence has been reported variably. Available data from England, Panama, Italy, the Netherlands, and other developed and underdeveloped countries report HPV infections to be at least as common as in the US. I.3 Mortality and Morbidity

Mortality is secondary to malignant transformation to carcinoma in both males and females. This oncogenic potential has been reported to triple the risk of genitourinary

cancer among infected males. Fortunately, this is rare with HPV types 6 and 11, which are the most commonly isolated viruses.

HPV infection appears to be more common and worse in patients with various types of immunologic deficiencies. Recurrence rates, size, discomfort, and risk of oncologic progression are highest among those patients. Secondary infection is uncommon.

Latent illness often becomes active during pregnancy. Vulvar condyloma acuminata may interfere with parturition. Trauma then may occur, producing crusting or erythema. Bleeding has been reported in large lesions that can occur during pregnancy.

In males, bleeding has been reported due to flat warts of the penile urethral meatus, usually associated with HPV-16. Lesions may lead to disfigurement of area(s) involved. Finally, acute urethral obstruction in women also may occur.

I.4 Distribution Sex: both sexes are susceptible to infection. Overt disease may be more common in men (reported in 75% of patients); however, infection may be more prevalent in women. Age: prevalence is greatest in persons aged 17-33 years, with incidence peaking in persons aged 20-24 years. Race: most studies indicate that no racial predilection exists for the acquisition of genital warts. Dinh and associates analyzed data from the 1999-2004 National Health and Nutrition Examination Surveys which collect data from a random sample of the United States civilian population. These investigators reported that non-Hispanic whites had a higher prevalence of genital warts when compared with other racial/ethnic groups.3

II CONTENT

II.1 Etiology Condylomata acuminata (CA) is a common sexually transmitted disease. 4 Condyloma acuminata are usually cauliflowerlike masses found on the urethra, penis, female genitalia, perianal area, or rectum. The lesions are typically limited to a few centimeters in diameter at the time of presentation to physicians.5 Condyloma are caused by the Human Papilloma Virus (HPV). Human papillomaviruses, or HPV, nonenveloped, double-stranded, circular DNA viruses of the family Papovaviridae are the etiologic agents of all types of wart.6 There are over 100 subtypes of HPV based on differences in DNA sequences. Approximately 40 subtypes are associated with genital tract infection. These are divided into low-risk types (e.g., HPV 6 and 11), which are most commonly found in patients with condyloma acuminatum (i.e., genital warts) and high-risk types (e.g., HPV 16 and 18) associated with approximately 70% of invasive cervical cancers and over 90% of high-grade intraepithelial lesions.7,8 In adults, types 1 to 4 are associated with common skin warts, types 6 and 11 with anogenital warts (that is, condylomata acuminata) and types 16 and 18 with cervical carcinoma.6

Condyloma are usually transmitted sexually, that is, passed through direct sexual contact with someone who has the warts. There are certain strains of the virus which are not necessarily sexually transmitted; that is, they may be contracted merely by getting the virus on your hands and then transmitting it to the genital area. All sexual partners need to be examined to rule out the virus. The male partner has a 70% chance of having warts after repeated sexual relations with an infected female partner.4 Another study found that 20% of uncircumcised and 5.5% of circumcised sexually active men had penile HPV by PCR (polymerase chain reaction).7

Perinatal transmission of HPV, occurring in utero and during passage of the neonate through an HPV-infected birth canal, probably accounts for most cases of condylomata acuminata in children younger than 2 years of age. In prepubertal children, other potential transmission

mechanisms include autoinoculation and heteroinoculation from nongenital cutaneous warts and from contaminated fomites. Although anogenital warts are considered to be sexually transmitted in adults, this may not be the case for children. Subtype specificity is less distinct in children than it is in adults. The most common types of HPV in condylomata from prepubertal children with or without proven sexual abuse are types 6 and 11, followed by type 2.6

II.2 Pathogenesis A wart is an epidermal tumor caused by HPV, one of the papovavirus family. It is now known that there are more than 60 specific types of HPV; nucleic acid hybridization studies are required to identify the type by its DNA. The differentiation has some clinical significance, such as the external anogenital skin is usually infected with types 6 and 11 (that is condyloma acuminata).9 HPV infection occurs through inoculation of virus into the viable epidermis through defects in the epithelium. Althought the cellular receptors for HPV has not been identified, cell surface heparan sulfate, which is encoded by proteoglycans and binds PV particles with high affinity, is required for entry. To establish persisitent infection, it is probably necessary to enter an epidermal basal cell that is either a stem cell or is converted by the virus to one with stem celllike properties. It is believed that a single copy or at most a few copies of the genome are maintained as an extrachromosomal plasmid within the infected epithelial basal cells. When these cells divide, the viral genome is also replicated and partitioned to each progeny cell, then transported within the replicated cells as they migrate upward to form diffrentiating layers. The rough surface of wart may disrupt adjacent skin and enable inoculation of virus into adjacent sites, with the debelopment of new warts ober a periods of weeks to months. Viral RNA expression (transcription) is extremely low until the upper Malphigian layer, just before the granular layer, where viral DNA synthesis typically results in hundreds of copies of viral genomes per cell. The viral capsid proteins are synthesized viral DNA is packaged into the virions in the nuclei of these differentiated Malphigian cells. A viral protein called E1-E4 may induce colapse of the cytoplasmic keratin filaments network. This postulated to facilitate release of the virions from the crossed-linked cytoskeleton of keratiniocytes so that virus can be inoculated into another site or desquamated into the environtment.

PV do not bud from the nuclear or plasma membrane, as do many viruses. PV virions are resistant to desiccarion and to the detergents nonoxynol-9, althought exposure of of virions to formalin, strong detergents such as sodium dodexyl sulfate, or prolonged reduce their infectivity. PVs can remain infectious for years when stored in glycerol at room temperature. Indeed, L1 and L2 from tightly packaged, very stable protein capsid. The states of differentiation of the infected epithelial cell influences viral transcription, signals initiation of viral DNA synthesis, and permits virion assembly. Further support for the belief that the production of virus particles depends on the states of epithelial differentiation is the fact that the virion production decreases as benign papilomas progress toward dysplasia. Because viral replication occurs in upper levels of the epithelium composed of replicating keratinocytes, PVs must block terminal differentiation and stimulate cell division to provide the enzymes and co-factor necessary for replication of viral DNA. Experimental evidence from cell culture systems has shown that PV proteins can alter cell proliferation and inhibit cell death via apoptosis.10 II.3 Clinical Feature Smoking, oral contraceptives, multiple sexual partners, and early coital age are risk factors for acquiring condyloma acuminata. Generally, two thirds of individuals who have sexual contact with a partner with condyloma acuminata develop lesions within 3 months. The chief complaint usually is one of painless bumps, pruritus, or discharge. Involvement of more than 1 area is common. History of multiple lesions, rather than 1 isolated wart, is common. Oral, laryngeal, or tracheal mucosal lesions (rare) presumably are transferred by oral-genital contact. History of anal intercourse in both males and females warrants a thorough search for perianal lesions. Rarely, urethral bleeding or urinary obstruction may be the presenting complaint when the wart involves the meatus. The patient's history may indicate presence of previous or other current STDs. Coital bleeding may occur. Vaginal bleeding during pregnancy may be due to condyloma eruptions. Latent illness may become active, particularly with pregnancy and immunosuppression. Lesions may regress spontaneously, remain the same, or progress. Pruritus may be present. Discharge may be a complaint.

Single or multiple papular eruptions may be observed. Eruptions may appear pearly, filiform, fungating, cauliflower, or plaquelike. They can be quite smooth (particularly on penile shaft), verrucous, or lobulated. Eruptions may seem harmless or may have a disturbing appearance. Carefully search for simultaneously involved multiple sites. Eruptions' color may be the same as the skin, or they may exhibit erythema or hyperpigmentation. Check for irregularity in shape, form, or color suggestive of melanoma or malignancy. Search for evidence of other STDs (eg, ulcerations, adenopathy, vesicles, discharge). Look for perianal lesions, particularly in patients with history or risk of immunosuppression or anal intercourse. Genital warts often occur in clusters and can be very tiny or can spread into large masses in the genital or penis area. In other cases they look like small stalks. In women they occur on the outside and inside of the vagina, on the opening (cervix) to the womb (uterus), or around (or inside) the anus. They are approximately as prevalent in men but the symptoms may be less obvious. When present, they usually are seen on the tip of the penis. They also may be found on the shaft of the penis, on the scrotum, or around (or inside) the anus. Rarely, genital warts also can develop in the mouth or throat of a person who has had oral sex with an infected person The viral particles are able to penetrate the skin and mucosal surfaces through microscopic abrasions in the genital area, which occur during sexual activity. Once cells are invaded by HPV, a latency (quiet) period of months to years (decades) may occur. HPV can last for several years without a symptom. Having sex with a partner whose HPV infection is latent and demonstrates no outward symptoms still leaves one vulnerable to becoming infected. If an individual has unprotected sex with an infected partner, there is a 70% chance that he or she will also become infected. The immune system eventually clears the virus through interleukins, which recruit interferons, which slow viral replication. II.4 Diagnosis II.4.1 History

Most patients seek medical care when they notice lumps on the vulva, perianal area, or periclitoral area.These lesions are generally not painful, but they can be associated with

pruritus.Bleeding can be observed if the lesions become confluent and are irritated by clothing. II.4.2 Physical

Inspection of the female genital area requires good lighting.On gross inspection, typical condyloma is usually a discrete papillary growth that arises from a single stalk.Condyloma acuminata can involve a large area in a sessile fashion.Subclinical infection is another common presentation of condyloma. Tiny, slightly raised areas can be felt or visualized on the vagina or cervix.These flat warts are best visualized using 3-5% acetic acid and a colposcope. Area infected with HPV appear acetowhite.Often, a biopsy is needed to distinguish these lesions from cervical squamous intraepithelial lesions or vaginal intraepithelial lesions.The sexual partner or partners of a woman with condyloma should be examined by a physician and treated if indicated.Often the examination of the male fails to reveal any visible condyloma. II.4.3 Causes

Approximately 30 different types of HPV can infect the anogenital tract.Infection caused by the.HPV virus results in local infections and appears as warty papillary condylomatous lesions. HPV infections in the genital area are sexually transmitted. II.4.4 Diagnosis Differential

Chanchroid.Herpes Simplex , Malignant Vulvar Lesions , Paget Disease Condyloma lata, Hymenal remnants, Immature squamous metaplasia, Micropapillomatosis labialis, Molluscum contagiosum, Seborrheic keratosis, Skin tags, Squamous hyperplasia, Verrucous carcinoma, Vulvar dysplasia. II.4.5 Lab Studies Patients who present with condyloma acuminata do not necessarily need other laboratory studies.Patients who are diagnosed with condyloma are at an increased risk for other STDs. Consider testing for chlamydia, gonorrhea, syphilis, hepatitis B, hepatitis C, herpes, HIV depending on the clinical situation. Finding a cauliflower-like growth on the genitals is reason to see a doctor who can tell if it is or a different kind of growth.The practitioner may

use a type of microscope called a colposcope to examine a woman's cervix to see if there are internal outbreaks.When acetic acid (vinegar) is swabbed on the cervix or penis, HPV lesions appear whitish. Colposcopy can be valuable in detecting flat lesions that are not visible to the unaided eye, but only two-thirds of white areas seen in a colposcope are due to HPV infection. Sampling cells with a biopsy and testing for HPV genetic material, may be necessary to confirm a diagnosis. These patients need a Papanicolaou (Pap) test of the cervix if one has not been performed in the last 12 months. In both of these scenarios, HPV typing can detect low-risk and high-risk HPV types found in the cervix. Currently, the 2 most accurate methods use 2 consensus primer polymerase chain reaction (PCR) systems. The commercially available system is the Hybrid Capture II system with differential testing for 9 high-risk HPV types and 5 low-risk HPV types.Testing for HPV confirmation of equivocal vulvar histology results provides an objective method for confirming a diagnosis of condyloma acuminate.

II.5 Therapy II.5.1 Prehospital Care Generally, prehospital care is unwarranted and inappropriate; however, reassure the patient and search for the possibility of another underlying reason prehospital care was requested. II.5.2 Emergency Department Care Type of workup, treatment regimens, and necessary follow-up care for condyloma acuminata generally are far beyond the scope of ED practice. However, the following procedures may be implemented if indicated: o Use pressure to stop any bleeding. o Relieve urethral obstruction in rare cases. o Reassure the patient. o Search for evidence of other coexistent STDs and treat if found. o Do not begin treatment of condyloma in the ED.

Although not ED treatments, the following are listed strictly for educational purposes and to assist readers in understanding and managing potential presenting complications of condyloma acuminata. Further details on management are included in the Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines.3 o Cryotherapy Cryotherapy may be performed using an open spray or cotton-tipped applicator for 10-15 seconds and repeated as needed. Lift away mobile skin from underlying normal tissue before freezing. Cryotherapy is an excellent first-line treatment, particularly for perianal lesions. Response rates are high with few adverse sequelae. Adverse reactions include pain at time of treatment, erosion, ulceration, and postinflammatory hypopigmentation of skin. Cryotherapy is safe during pregnancy. o Electrodesiccation: Smoke plume potentially may be infective. o Curettage o Surgical excision Excision has highest success rate and lowest recurrence rate. Initial cure rates are 63-91%.

o Carbon dioxide laser treatment Use carbon dioxide laser treatment for extensive or recurrent condyloma acuminata. Potentially infectious HPV-6 DNA has been detected in the carbon dioxide laser plume. Local, regional, or general anesthesia is required. Eutectic mixture of local anesthetics (EMLA) cream may be used as an alternative anesthetic. II.5.3 Medication

Cytotoxic agents Inhibit proliferation of cells at various stages of the cell cycle.

Podophyllum resin (Podocon-25, Pod-Ben-25) Extract of various plants, which are cytotoxic. Effective in arresting mitosis in metaphase. Expect cure rate of 20-50% if used as single agent.

Podofilox (Condylox) Purified podophyllotoxin that is antimitotic, cytotoxic, and available for patient's home use. While exact mechanism of action on condyloma is unknown, podofilox results in necrosis of genital condyloma acuminata. Condylox is one agent containing podofilox. Slightly higher cure rates can be expected with podofilox than with podophyllin. Additionally, useful for prophylaxis. In adult, apply 0.5% solution bid for 3 consecutive day and discontinue for 4 day, not to exceed 4 wk. Use <0.5 mL of solution or 0.5 g of gel/d; treat <10 cm2 of tissue per day; wash hands thoroughly after each application

Trichloroacetic or bichloracetic acids No longer recommended for routine use. Has antimetabolic and/or antineoplastic and immunostimulative activity. Useful in prevention of recurrence after condyloma ablation if started within 4 wk, especially in immunocompromised patients.In adult, administer 5% cream qd or periodically for 10 wk; apply 1% cream bid for 2-6 wk; mild local discomfort can be treated with cortisol cream; topical 5-FU is best option for preventing recurrence in immunocompromised patients; in general, no systemic adverse effects exist; however, prolonged use results in erosive dermatitis and mucositis; additionally, risk of vaginal adenosis and clear cell adenocarcinoma exists.

Bleomycin (Blenoxane) Composed of cytotoxic glycopeptide antibiotics, which appear to inhibit DNA synthesis with some evidence of RNA and protein synthesis inhibition to a lesser degree; used in management of several neoplasms as a palliative measure; may cause a variety of adverse effects; observe patients frequently and carefully during and after treatment. In adult, reconstitute Blenoxane 15-U vial with 1-5 mL of sterile water or NS for injection; administer intralesionally.

Imiquimod (Aldara) Induces interferon production and is a cell-mediated immune response modifier. Has minimal systemic absorption but causes erythema, irritation, ulceration, and pain. Burning, erosion, flaking, edema, induration, and pigmentary changes may occur at application site. Imiquimod 5% cream comes in single-use packets. In adult, apply at bedtime for 3 day, then rest 4 day; alternatively, may apply qod for 3 applications; may repeat weekly cycles up to 16 wk (Patients should apply thin layer to external, visible warts, then rub in cream until vanishes. Area is washed with soap and water 6-10 h after treatment.)

Interferons Interferons are not recommended as a primary treatment modality. Naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons exist and may be administered topically, systemically, and intralesionally. Topical, systemic, and intralesional interferons are not efficacious.

Interferon alfa-n3 (Alferon N) Alpha interferon has been approved by FDA for injectional use in refractory condyloma acuminata with some possible benefit. Alferon N is interferon alpha-n3, which has been used effectively for this purpose. Recurrence rate of 20-40% exists with intralesional interferon, but recurrence rate after successful treatment is lower than with other treatment modalities. Additionally, intralesional interferon is expensive and requires repeat office visits. Furthermore, numerous adverse reactions may occur, including myalgias, fever, chills, GI symptoms, transient leukopenia, thrombocytopenia, LFT abnormalities, serum lipid abnormalities with intramuscular interferon, and theoretical risk of viral transmission with natural interferon products. Viral symptoms do abate with time, and all adverse effects resolve once therapy is stopped. Viral symptoms can be treated with acetaminophen or NSAIDs in the interim. In adult, administer interferon alpha-n3 250,000 U/wart intralesionally twice/wk for up to 8 wk; not to exceed 2.5

million U per treatment session. In pediatric if the patient <18 years: Not recommended; >18 years: Administer as in adults. Miscellaneous topical ointment Another topical product that has gained FDA approval for genital warts includes kunecatechins. Kunecatechins (Veregen) Botanical drug product for topical use consisting of extract from green tea leaves. Mode of action unknown but does elicit antioxidant activity in vitro. Indicated for topical treatment of external genital and perianal warts (condylomata acuminatum) in immunocompetent patients. In adult, apply topically tid; use approximately a 0.5-cm strand of ointment topically for each external genital or perianal wart. Vaccines A human papillomavirus vaccine is now available for prevention of HPV-associated dysplasias and neoplasia including cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions. The immunization series should be completed in boys, girls, and young men and women aged 9-26 years. Papillomavirus vaccine (Gardasil) Quadrivalent human papillomavirus (HPV) recombinant vaccine.

First vaccine indicated to prevent cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions (eg, cervical adenocarcinoma in situ; cervical intraepithelial neoplasia grades 1, 2, and 3; vulvar intraepithelial neoplasia grades 2 and 3; vaginal intraepithelial neoplasia grades 2 and 3) due to HPV types 6, 11, 16, and 18. Vaccine efficacy mediated by humoral immune responses following immunization series. Indicated for prevention of condyloma acuminata caused by HPV types 6 and 11 in boys, men, girls, and women aged 9-26 years. In adult, <26 years: 0.5 mL IM administered as 3 separate doses; administer second and third doses 2 and 6 mo after first dose,

respectively >26 years: Not established. In pediatric if the patient <9 years: Not established; >9 years: Administer as in adults.

III
CONCLUTION

Condyloma acuminata or Genital warts is a highly contagious sexually transmitted disease. It is refers to an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV). Approximately 90% of condyloma acuminata are related to HPV types 6 and 11 which have neoplastic potential. This disease usually cauliflower like masses found on the urethra, penis, female genitalia, perianal area, or rectum. In perinatal transmission, these diseases transmit through utero and during passage of the neonate through an HPV-infected birth canal. For prepubertal children, other potential transmission mechanisms include autoinoculation and heteroinoculation from nongenital cutaneous warts and from contaminated fomites. Mortality is secondary to malignant transformation to carcinoma in both males and females. HPV infection appears to be more common and worse in patients with various types of immunologic deficiencies. The diagnosis of condyloma acuminate can be done by taking full medical history, complete anamnesis, physical examination, and laboratory examination. Inspection of the area that has been suspect with this disease is really good approach. Finding a cauliflower like growths on the genitals indicate that person suspected with the condyloma acuminate then maybe need to get another laboratory examination to roll out other STDs. Usually individual which already exposed to the disease will developed the symptom within 3 month after the contacted. Painless bumps, pruritus, or discharge usually is the common chief compliant of the early symptoms of condyloma acuminata. Single or multiple papular eruptions may appear pearly, filiform, fungating, cauliflower, or plaquelike which can be quite smooth, verrucous, or lobulated. Smoking, oral contraceptives, multiple sexual partners, and early coital age are risk factors for acquiring condyloma acuminata. Basically is no cure for HPV, but there are methods to treat visible warts, which could reduce infectivity. Depending on the sizes and locations of warts there is several ways to treat them. Podofilox is the first-line treatment due to its low cost. Cytotoxic agents usually use to inhibit proliferation of cells at various stages of the cell cycle like Podophyllum resin. An Imiquimod (Aldara) and Trichloroacetic or bichloracetic acids also has been use in treatment of candyloma acuminata. Interferon alfa-n3 (Alferon N) are using in treatment for adult and in a children. Liquid nitrogen cryosurgery is safe for using in pregnancy.

The only way to prevent HPV infection is to avoid direct contact with the virus, which is transmitted by skin-to-skin contact.

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